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1910.01108 | 0 | usb predictive biomarkers ovarian cancer google patent usb predictive biomarkers ovarian cancer google patent predictive biomarkers ovarian cancer download pdf info publication number usb usb u usa usb u b u b u b u u u u b u b u b authority u united state prior art keywords cancer ovarian cancer biomarkers reagent ovarian prior art date legal status legal status assumption legal conclusion google performed legal analysis make representation accuracy status listed active application number u version usa en inventor brian c mansfield ping f yip suraj amonkar greg p bertenshaw current assignee listed assignee may inaccurate google performed legal analysis make representation warranty accuracy list aspira woman health inc original assignee vermillion inc priority date priority date assumption legal conclusion google performed legal analysis make representation accuracy date listed filing date publication date family litigation priority claimed usp externalpriority first worldwide family litigation filed litigation critical global patent litigation dataset dartsip licensed creative common attribution international license priority u priority critical patentusben application filed vermillion inc filed critical vermillion inc assigned vermillion inc reassignment vermillion inc assignment assignor interest see document detail assignor correlogic system inc assigned correlogic system inc reassignment correlogic system inc assignment assignor interest see document detail assignor amonkar suraj bertenshaw greg p mansfield brian c yip ping f publication usa publication critical patentusaen priority u priority patentusaen publication usb publication critical patentusben application granted granted critical assigned aspira woman health inc reassignment aspira woman health inc change name see document detail assignor vermillion inc status active legalstatus critical current anticipated expiration legalstatus critical link uspto uspto patentcenter uspto assignment espacenet global dossier discus classification gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnspecifically defined cancer gnspecifically defined cancer ovary gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite involving compound localized membrane tumor cancer cell gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gndetermining risk developing disease gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gnpredicting monitoring response treatment eg selection therapy based assay result personalised medicine prognosis gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gncomplex way combining multiple protein biomarkers diagnosis ygeneral tagging new technological development general tagging crosssectional technology spanning several section ipc technical subject covered former uspc crossreference art collection xracs digest ytechnologies application mitigation adaptation climate change yatechnologies adaptation climate change yatechnologies indirect contribution adaptation climate change yainformation communication technology ict supporting adaptation climate change eg weather forecasting climate simulation ya ya abstract method provided predicting presence subtype stage ovarian cancer well assessing therapeutic efficacy cancer treatment determining whether subject potentially developing cancer associated test kit computer analytical system well software diagnostic model also provided description cross reference related application application continuation u patent application ser filed feb u pat issued dec continuation u patent application ser filed feb u pat issued mar divisional u patent application ser filed jun u pat issued mar claim priority usc section provisional patent application serial no filed jun filed mar disclosure hereby incorporated reference entirety field invention invention provides method predicting diagnosing ovarian cancer particularly epithelial ovarian cancer provides associated analytical reagent diagnostic model test kit clinical report background american cancer society estimate ovarian cancer strike woman take life woman united state ovarian cancer single disease however actually type subtypes ovarian malignancy | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 1 | pathology clinical behavior expert therefore group ovarian cancer within three major category according kind cell formed epithelial tumor arise cell line cover ovary germ cell tumor originate cell destined form egg within ovary sex cordstromal cell tumor begin connective cell hold ovary together produce female hormone common epithelial tumor begin surface epithelium ovary account percent ovarian cancer u following percentage reflect u prevalence cancer divided number subtypesincluding serous endometrioid mucinous clear cell tumorsthat subclassified benign malignant tumor serous tumor widespread form ovarian cancer account percent common epithelial tumor percent serous tumor malignant percent benign percent borderline malignancy serous tumor occur often woman year age endometrioid tumor represent approximately percent common epithelial tumor percent individual cancer associated endometrial carcinoma cancer womb lining percent case also linked endometriosis abnormal occurrence endometrium womb lining tissue within pelvic cavity majority percent tumor malignant remainder roughly percent usually borderline malignancy endometrioid tumor occur primarily woman year age clear cell tumor account percent common epithelial tumor nearly tumor malignant approximately onehalf clear cell tumor associated endometriosis patient clear cell tumor year age mucinous tumor make percent common epithelial tumor approximately percent tumor benign percent borderline malignancy percent malignant mucinous tumor appear often woman year age ovarian cancer far deadly gynecologic cancer accounting percent gynecologic cancer death ovarian cancer also among treatableif caught early ovarian cancer caught early appropriately treated year survival rate percent see example luce et al early diagnosis key epithelial ovarian cancer detection nurse practitioner december p extensive background information ovarian cancer readily available internet example overview ovarian cancer cancer reference information provided american cancer society wwwcancerorg nccn clinical practice guideline oncology ovarian cancer v wwwnccnorg current reality diagnosis ovarian cancer case percent case ovarian cancerare caught earliest stage early stage ovarian cancer difficult diagnose symptom may appear noticed point symptomssuch bloating indigestion diarrhea constipation othersmay vague associated many common le serious condition importantly effective test early detection effective tool early accurate detection ovarian cancer critical unmet medical need biomarkers ovarian cancer variety biomarkers diagnose ovarian cancer proposed elucidated variety technology platform data analysis tool interesting compilation potential protein biomarkers various pathology presented n leigh anderson et al target list candidate biomarkers targeted proteomics biomarker insight spreadsheet listing marker discussed paper found website plasma proteome institute wwwplasmaproteomeorg several published study described immediately number study listed reference end specification study document cited specification related provisional patent application ser no filed jun filed mar hereby incorporated reference entirety example cole method detecting onset progression regression gynecologic cancer u pat oct described method detecting presence gynecologic cancer female said cancer selected group consisting cervical cancer ovarian cancer endometrial cancer uterine cancer vulva cancer method comprising step assaying plasma tissue sample patient presence ca time b assaying bodily nonblood sample said patient presence human chorionic gonadotropin betasubunit core fragment wherein detection ca human chorionic gonadotropin betasubunit core fragment indication presence gynecological cancer female measurement human chorionic gonadotropin betasubunit core fragment alone stated useful monitoring progression regression cancer fung et al biomarker ovarian endometrial cancer hepcidin u patent application published mar describes method qualifying ovarian endometrial cancer status based measuring hepcidin single biomarker based panel marker including hepcidin plus transthyretin two marker plus least one biomarker selected group consisting apo transferrin ctapiii itih fragment additional panel includes beta microglobulin biomarkers measured mass spectrometry particularly seldims immunoassay data analyzed roc curve analysis fung et al also described use hepcidin level used combination biomarkers concluded predictive power test improved specifically increased level hepcidin together | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 2 | decreased level transthyretin correlated ovarian cancer increased level hepcidin together decreased level transthyretin together level one apo decreased level transferrin decreased level ctapiii elevated level internal fragment itih elevated level also correlated ovarian cancer foregoing biomarkers combined beta microglobulin elevated level ca elevated level andor known ovarian cancer biomarkers use disclosed diagnostic test hepcidin said hepcidin transthyretin said cysteinylated transthyretin andor itih fragment perhaps itih fragment diamandis multiple marker assay detection ovarian cancer u patent application published jun described method detecting plurality kallikrein marker associated ovarian cancer optionally ca wherein kallikrein marker comprise selected group consisting kallikrein kallikrein kallikrein kallikrein kallikrein kallikrein patent application explained significant difference level kallikreins subgroup secreted serine protease marker optionally also ca relative corresponding normal level indicative ovarian cancer repeatedly sampling marker patient time diamandis also found significant difference level kallikrein marker optionally ca later sample relative earlier sample indication patient therapy efficacious inhibiting ovarian cancer sample evaluated protein binding technique example immunoassay nucleotide array pcr like technique gorelik et al multiplexed immunobeadbased cytokine profiling early detection ovarian cancer cancer epidemiol biomarkers prev april reported panel multiple cytokine separately may show strong correlation disease provide diagnostic potential related patent application appears lokshin et al multifactorial assay cancer detection u patent application published mar according journal article novel multianalyte labmap profiling technology employed allowed simultaneous measurement multiple marker various concentration cytokine cytokineschemokines growth angiogenic factor combination ca measured blood serum patient earlystage ovarian cancer healthy woman patient benign pelvic tumor cytokine discussed gorelik et al six marker specifically interleukin il il epidermal growth factor egf vascular endothelial growth factor vegf monocyte chemoattractant protein mcp together ca showed significant difference serum concentration ovarian cancer control group marker il il vegf egf ca used classification tree analysis reportedly resulted sensitivity specificity receiver operator characteristic curve roc described using combination marker produced sensitivity specificity interestingly receiver operator characteristic curve ca alone resulted sensitivity classification tree analysis described paper discrimination benign condition ovarian cancer used ca granulocyte colonystimulating factor gcsf il egf vegf resulted sensitivity specificity author concluded simultaneous testing panel serum cytokine ca using labmap technology presented promising approach ovarian cancer detection related patent application lokshin enhanced diagnostic multimarker serological profiling u patent application published feb describes various biomarker panel associated method diagnosis ovarian cancer one method involves determining level least four marker blood patient least two different marker selected ca prolactin human epididymis protein svcam tsh third marker fourth marker selected ca prolactin iie svcam tsh cytokeratin sicam igfbp eotaxin fsh third marker fourth marker selected listed marker different different either first second marker dysregulation least four marker indicates high specificity sensitivity diagnosis ovarian cancer another panel includes least eight marker blood patient wherein least four different marker selected group consisting ca prolactin svcam tsh wherein fifth marker sixth marker seventh marker eighth marker selected group consisting ca prolactin svcam tsh cytokeratin sicam igfbp eotaxin fsh wherein said fifth marker said sixth marker said seventh marker said eighth marker different different said least four marker wherein dysregulation said least eight marker indicates high specificity sensitivity diagnosis ovarian cancer lokshin patent application also describes blood marker panel comprising two egf epidermal growth factor gcsf granulocyte colony stimulating factor il il ca cancer antigen vegf vascular endothelial growth factor mcpi monocyte chemoattractant protein antiil antiil antica anticmyc antip anticpa antica antimuc antisurvivin antibhcg antiosteopontin antipdgf antiherneu antiakt anticytokeratin cytokeratin egfr cea kallikrein mcsf fasl erbb herneu sample patient blood presence two following condition indicated presence ovarian cancer patient egf low gcsf high il high il high vegf high mcp low antiil high antiil high antica high anticmyc high antipsup high anticea high antica high antimuc high antisurvivin high antibhcg high antiosteopontin high antiherneu high antiakt high anticytokeratin high antipdgf high ca high cytokeratin high egfr low hcrneu low cea high fasl high kallikrein low erbb low mcsf low exemplary panel include without limitation ca cytokeratin fasl mcsf cytokeratin cea fa egfr kallikrein cea fa mcsf egfr ca cytokeratin | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 3 | kallikrein cea ca mcsf kallikrein egfr ca cytokeratin cea ca mcsf egfr cytokeratin kallikrein ca mcsf fasl cytokeratin kallikrein cea mcsf cytokeratin kallikrein cea ca ca cytokeratin erbb egf gcsf il il vegf mcp antica antiil antisurvivin antip anti cmyc antica antiil antisurvivin antip anti cmyc anticea antiil antiegf antibhcg chan et al use biomarkers detecting ovarian cancer u published patent application published mar describes method qualifying ovarian cancer status subject comprising measuring least one biomarker sample subject wherein biomarker selected group consisting apoa transthyretin deltan iaih fragment combination thereof b correlating measurement ovarian cancer status another embodiment chan application described additional biomarker selected ca ca ii ca ca ca ca tumor associated trypsin inhibitor tati cea placental alkaline phosphatase plap sialyl tn galactosyltransferase macrophage colony stimulating factor mcsf csf lysophosphatidic acid lpa kd component extracellular domain epidermal growth factor receptor pegfr tissue kallikreins example kallikrein kallikrein ne prostasin creatine kinase b ckb lasa herneu urinary gonadotropin peptide dianon nb k tissue peptide antigen tpa osteopontin haptoglobin protein variant eg cleavage form isoforms marker elisabased blood serum test described evaluation four protein useful early diagnosis epithelial ovarian cancer leptin prolactin osteopontin insulinlike growth factor author reported single protein could completely distinguish cancer group healthy control group however combination four protein provided sensitivity positive predictive value ppv specificity negative predictive value npv said considerable improvement current methodology mor et al serum protein marker early detection ovarian cancer pnas related patent application mor et al identification cancer protein biomarkers using proteomic technique u patent application published sep describes biomarkers identified using novel screening method biomarkers stated discriminate cancer healthy subject well useful prognosis monitoring cancer specifically abstract patent application relates use leptin prolactin opn igfii purpose disclosed invention somewhat generally characterized involving comparison expression one biomarkers sample selected group consisting ckine ace bdnf ca eselectin egf eot erbb follistatin hcc hvem igfii igfbp il ilsrii ilsra leptin mcsf r mif mipa mipb mmp mmp mpif opn parc pdgf rb prolactin proteinc tgfb riii tnfr tnfa vap vegf r vegf r significant difference expression one biomarkers sample compared predetermined standard said diagnose aid diagnosis cancer patent application le page et al method diagnosing ovarian cancer kit therefor wo published mar describes method determining whether subject affected ovarian cancer detecting expression level fgf ca optionally il approach described patent scientific literature include analysis expression particular gene transcript blood cell see example liew method detection cancer related gene transcript blood u published patent application jun although gene transcript specific ovarian cancer identified transcript table j k x said indicate presence cancer see also tchagang et al early detection ovarian cancer using group biomarkers mol cancer ther another diagnostic approach involves detecting circulating antibody directed tumorassociated antigen see nelson et al antigen panel method using u patent application published oct robertson cancer detection method regent u patent application published dec urgently needed field gynecologic oncology minimally invasive preferably serumbased clinical test assessing predicting presence ovarian cancer based robust set biomarkers sample feature identified large diverse set sample together method associated computer system software tool predict diagnose monitor ovarian cancer high accuracy various stage summary invention present invention generally relates cancer biomarkers particularly biomarkers associated ovarian cancer provides method predict evaluate diagnose monitor cancer particularly ovarian cancer measuring certain biomarkers provides set array reagent evaluate expression level biomarkers associated ovarian cancer preferred set biomarkers provides detectable molecular signature ovarian cancer subject invention provides predictive diagnostic test ovarian cancer particularly epithelial ovarian cancer particularly earlystage ovarian cancer stage stage ii stage ii together specifically predictive test associated method product also provide useful clinical information regarding stage ovarian cancer progression stage stage ii stage iii stage iv advanced stage reflects relatively advanced tumor readily classified either stage iii stage iv overall invention also relates newly discovered correlation relative level expression certain group marker bodily fluid preferably blood serum plasma subject ovarian cancer status one embodiment invention provides set reagent measure expression level panel set biomarkers fluid sample drawn patient blood serum plasma lymph cerebrospinal fluid ascites urine reagent embodiment | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 4 | multianalyte panel assay comprising reagent evaluate expression level biomarker panel embodiment invention subject sample prepared tissue sample tissue biopsy primary cell culture culture fluid embodiment expression biomarkers determined polypeptide level related embodiment utilize immunoassay enzymelinked immunosorbent assay multiplexed immunoassay purpose preferred panel biomarkers selected group consisting following set molecule measurable fragment myoglobin crp c reactive protein fgf basic protein ca b hepatitis c n ribosomal p antibody crp c ca tgf alpha enrage egf hsp alpha antibody enrage egf ca fibrinogen apolipoprotein ciii egf cholera toxin ca e proteinase canca antibody fibrinogen ca egf cd tsh leptin ca lymphotactin f ca egfr crp il apolipoprotein ciii tenascin c apolipoprotein g ca beta microglobulin crp ferritin timp creatine kinasemb il h ca egfr il haptoglobin crp insulin timp ferritin alpha macroglobulin leptin il ctgf enrage lymphotactin tnfalpha igf tnf rii von willebrand factor mdc ca crp egfr ca apoai apociii il il mipa tenascin c myoglobin j ca crp egfr ca apoai apociii il mipa tenascin c myoglobin k biomarker panel presented table ii table iii another embodiment reagent measure biomarkers may measure molecular specie found upstream downstream biochemical pathway measure fragment biomarkers molecular specie instance reagent may accurately measure biomarker fragment another embodiment present invention relates binding molecule binding reagent measure biomarkers related molecule fragment contemplated binding molecule includes antibody monoclonal polyclonal aptamers like embodiment include binding reagent provided form test kit optionally together written instruction performing evaluation biomarkers predict likelihood ovarian cancer subject embodiment present invention provides method predicting likelihood ovarian cancer subject based detecting measuring level specimen biological sample subject foregoing biomarkers described specification change expression level biomarkers particularly relative expression level compared control group patient ovarian cancer predictive ovarian cancer subject aspect type ovarian cancer predicted serous endometrioid mucinous clear cell tumor prediction ovarian cancer includes prediction specific stage disease stage ia ib ic ii iii iv tumor yet another embodiment invention relates creating report physician relative level biomarkers transmitting report mail fax email otherwise embodiment data stream transmitted via internet contains report biomarker evaluation embodiment report includes prediction presence absence ovarian cancer subject stratified risk ovarian cancer subject optionally subtype stage cancer according another aspect invention foregoing evaluation biomarker expression level combined diagnostic purpose diagnostic procedure gastrointestinal tract evaluation chest xray test ca test complete blood count ultrasound abdominalpelvic computerized tomography blood chemistry profile liver function test yet embodiment invention relate evaluation sample drawn subject symptomatic ovarian cancer high risk ovarian cancer embodiment relate subject asymptomatic ovarian cancer symptomatic subject one following pelvic mass ascites abdominal distention general abdominal discomfort andor pain gas indigestion pressure swelling bloating cramp nausea diarrhea constipation frequent urination loss appetite feeling fullness even light meal weight gain loss known reason abnormal bleeding vagina level biomarkers may combined finding symptom diagnosis ovarian cancer embodiment invention highly accurate determining presence ovarian cancer highly accurate meant sensitivity specificity least percent higher preferably least percent percent preferably least percent percent accurate embodiment invention include method sensitivity least percent percent percent specificity least percent percent percent percent percent higher embodiment include method specificity least percent percent percent sensitivity least percent percent percent percent percent higher embodiment invention relating sensitivity specificity determined population subject symptomatic ovarian cancer ovarian cancer compared control group subject symptomatic ovarian cancer ovarian cancer another embodiment sensitivity specificity determined population subject increased risk ovarian cancer ovarian cancer compared control group subject increased risk ovarian cancer ovarian cancer another embodiment sensitivity specificity determined population subject symptomatic ovarian cancer ovarian cancer compared control group | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 5 | subject symptomatic ovarian cancer ovarian cancer aspect level biomarkers evaluated applying statistical method knowledge discovery engine kde regression analysis discriminant analysis classification tree analysis random forest proteomequest support vector machine one r knn heuristic naive bayes analysis neural net variant thereof another embodiment predictive diagnostic model based expression level biomarkers provided model may form software code computer readable format form written instruction evaluating relative expression biomarkers patient physician utilize report biomarker evaluation broader diagnostic context order develop relatively complete assessment risk given patient ovarian cancer making assessment physician consider clinical presentation patient includes symptom suspicious pelvic mass andor ascites abdominal distention symptom without another obvious source malignancy general lab workup symptomatic patient currently includes gi evaluation clinically indicated chest xray ca test cbc ultrasound abdominalpelvic ct clinically indicated chemistry profile lfts may include family history evaluation along genetic marker test brca brca see generally nccn clinical practice guideline oncology ovarian cancer v present invention provides novel important additional source information assist physician stratifying patient risk ovarian cancer planning next diagnostic step take present invention also similarly useful assessing risk ovarian cancer nonsymptomatic highrisk subject well general population screening tool contemplated method present invention may used clinician part overall assessment predictive diagnostic indicator present invention also provides method ass therapeutic efficacy existing candidate chemotherapeutic agent type cancer treatment appreciated person skilled art relative expression level biomarker panelsor biomarker profilesare determined described specimen taken subject prior treatment optionally progressive stage treatment change relative expression biomarkers noncancer profile expression level nearly noncancer expression profile stable nonchanging profile relative biomarker expression level interpreted therapeutic efficacy person skilled art readily understand profile expression level may become diagnostic cancer precancer premalignant condition simply move toward diagnostic profile relative ratio biomarkers become like cancerrelated profile previously another embodiment invention provides method determining whether subject potentially developing cancer relative level expression biomarkers determined specimen taken subject time whereby change biomarker expression profile toward cancer profile interpreted progression toward developing cancer expression level biomarkers specimen may stored electronically subject analysis completed recalled comparison purpose future time present invention provides method software product computer system network associated instrument provide highly accurate test ovarian cancer combination marker described specification provide sensitive specific accurate method predicting presence detecting ovarian cancer various stage progression evaluation sample described may also correlate presence premalignant preclinical condition patient thus contemplated disclosed method useful predicting detecting presence ovarian cancer sample absence ovarian cancer sample drawn subject stage ovarian cancer grade ovarian cancer benign malignant nature ovarian cancer metastatic potential ovarian cancer histological type neoplasm associated ovarian cancer indolence aggressiveness cancer characteristic ovarian cancer relevant prevention diagnosis characterization therapy ovarian cancer patient contemplated method disclosed also useful assessing efficacy one test agent inhibiting ovarian cancer assessing efficacy therapy ovarian cancer monitoring progression ovarian cancer selecting agent therapy inhibiting ovarian cancer monitoring treatment patient afflicted ovarian cancer monitoring inhibition ovarian cancer patient assessing carcinogenic potential test compound evaluating biomarkers test animal following exposure detailed description biomarker panel associated method product identified analysis analyte level various molecular specie human blood serum drawn subject ovarian cancer various stage subtypes subject noncancer gynecological disorder normal subject immunoassay described courteously performed colleague rulesbased medicine austin tex using multianalyte profile map luminex platform wwwrulesbasedmedicinecom preferred sample blood scrum contemplated appropriate sample derived biological source sample tissue extract cell culture including cell example tumor cell cell lysates physiological fluid example whole blood plasma serum saliva ductal lavage ocular lens fluid cerebral spinal fluid sweat urine milk ascites fluid synovial fluid peritoneal fluid like sample obtained animal preferably mammal preferably primate preferably human using specie specific binding agent equivalent discussed context human sample | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 6 | analysis contemplated technique marker panel may used evaluate drug therapy rodent animal including transgenic animal relevant development human veterinary therapeutic sample treated prior use conventional technique preparing plasma blood diluting viscous fluid like method sample treatment involve filtration distillation extraction concentration inactivation interfering component addition chaotropes addition reagent like nucleic acid including silencer regulatory interfering rna may isolated level expression analytes described also used method invention sample analytical platform set blood serum sample analyzed generate data discussed contained ovarian cancer sample nonovarian cancer sample subset sample used described ovarian cancer sample sample comprised following epithelial ovarian cancer subtypes serous clear cell endometrioid mucinous mixed consisting one subtype stage distribution ovarian cancer sample stage stage ii stage iii stage iv unknown stage nonovarian cancer sample set includes following ovarian condition benign normal ovary low malignant potentialborderline sample set also includes serum patient cancer cervical cancer endometrial cancer uterine cancer analyte level sample discussed specification measured using highthroughput multianalyte immunoassay platform preferred platform luminex map system developed rulesbased medicine inc austin tex described company website also example publication chandler et al method kit diagnosis acute coronary syndrome u patent application published jan related application spain et al universal shotgun assay u patent application published oct platform previously described lokshin generated data used analysis ovarian cancer biomarkers however immunoassay platform system may used brief describe preferred analyte measurement system map platform incorporates polystyrene microspheres dyed internally two spectrally distinct fluorochrome using accurate ratio fluorochrome array created consisting different microsphere set specific spectral address microsphere set display different surface reactant microsphere set distinguished spectral address combined allowing different analytes measured simultaneously single reaction vessel third fluorochrome coupled reporter molecule quantifies biomolecular interaction occurred microsphere surface microspheres interrogated individually rapidly flowing fluid stream pas two separate laser luminex analyzer highspeed digital signal processing classifies microsphere based spectral address quantifies reaction nil surface second per sample skilled artisan recognize wide variety analytical technique may used determine level biomarkers sample described claimed specification type binding reagent available person skilled art may utilized measure level indicated analytes sample example variety binding agent binding reagent appropriate evaluate level given analyte may readily identified scientific literature generally appropriate binding agent bind specifically analyte word reacts detectable level analyte react detectably reacts limited crossreactivity unrelated analytes contemplated appropriate binding agent include polyclonal monoclonal antibody aptamers rna molecule like spectrometric method also may used measure level analytes including immunofluorescence mass spectrometry nuclear magnetic resonance optical spectrometric method depending binding agent utilized sample may processed example dilution purification denaturation digestion fragmentation like analysis would known person skilled art also gene expression example tumor cell lymphocyte also may determined also contemplated identified biomarkers may multiple epitope immunoassay andor binding site type binding agent thus contemplated peptide fragment epitope identified biomarkers isoforms specific protein even compound upstream downstream biological pathway posttranslationally modified may substituted identified analytes biomarkers long relevant relative stoichiometry taken account appropriately skilled artisan recognize alternative antibody binding agent used determine level particular analyte long various specificity binding affinity factored analysis variety algorithm may used measure determine level expression analytes biomarkers used method test kit present invention generally contemplated algorithm capable measuring analyte level beyond measurement simple cutoff value thus contemplated result algorithm generically classified multivariate index analysis u food drug administration specific type algorithm include knowledge discovery engine kde regression analysis discriminant analysis classification tree analysis random forest proteomequest support vector machine one r knn heuristic naive bayes analysis neural net variant thereof analysis example following discussion example provided describe illustrate present invention construed limit scope invention skilled art well appreciate many embodiment also | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 7 | fall within scope invention described specification claim analysis data find informative biomarker panel using kde correlogic described use evolutionary pattern recognition algorithm evaluating complex data set including knowledge discovery engine kde proteomequest see example hitt et al u pat process discriminating biological state based hidden pattern biological data issued aug hitt u pat heuristic method classification issued aug hitt u pat heuristic method classification issued jul use technology evaluate mass spectral data derived ovarian cancer sample elucidated hitt et al multiple highresolution serum proteomic feature ovarian cancer detection u published patent application published mar analyzing data set correlogics knowledge discovery engine following fivebiomarker panel found provide sensitivity specificity various stage ovarian cancer set forth table specifically kde model returned relatively high accuracy stage ovarian cancer included marker cancer antigen ca swissprot accession number qrx c reactive protein crp swissprot accession number p fibroblast growth factorbasic protein fgfbasic swissprot accession number p myoglobin swissprot accession number p kde model returned relatively high accuracy stage iii iv advanced ovarian cancer included marker hepatitis c n antibody hep c n ab ribosomal p antibody crp kde model returned relatively high accuracy stage included marker ca tgf alpha enrage swissprot accession number p epidermal growth factor egf swissprot accession number p iisp alpha antibody kde model returned relatively high accuracy stage ii stage iii iv advanced ovarian cancer included marker enrage egf cancer antigen ca swissprot accession number q fibrinogen swissprot accession number alpha chain p beta chain p gamma chain p apolipoprotein ciii apociii swissprot accession number p cholera toxin ca kde model also returned relatively high accuracy stage ii stage iii iv advanced ovarian cancer included marker proteinase canca antibody fibrinogen ca egf cd swissprot accession number qph thyroid stimulating hormone tsh swissprot accession number alpha p beta p p leptin swissprot accession number p ca lymphotactin swissprot accession number p contemplated skilled artisan could use kde analytical tool identify potentially useful set biomarkers predictive diagnostic value based level selected analytes note kde algorithm may select utilize various marker based relative abundance given marker example level cholera toxin model iv may zero relevant combination marker selected particular grouping skilled artisan recognize limited size data set used specification may lead different result example different panel marker varying accuracy comparing relative performance kde analytical technique identify informative panel biomarkers particular kde model built relatively small data set using stage ovarian cancer normalbenigns tested blindly balance stage ii iiiiv described thus specificity stage sample reflects sample set size potential overfitting drop specificity balance nonovarian cancer sample also expected given relatively larger size testing set relative training set overall biomarker panel developed stage sample also provides potentially useful predictive diagnostic assay later stage ovarian cancer given high sensitivity value however example biomarker panel illustrate number parameter adjusted impact model performance instance case variety different number feature combined together variety match value used variety different length evolution genetic algorithm used model differing number node generated routine experimentation apparent one skilled art combination parameter used generate predictive model based biomarker panel clinically relevant performance table result analysis using knowledge discovery engine develop stage specific classification model sensitivity specificity accuracy sensitivity sensitivity model name feature match generation node stage stage stage stage ii stage iiiiv specificity method analysis find informative biomarker panel using random forest preferred analytical technique known skilled artisan breiman random forest machine learning described segel machine learning benchmark random forest regression robniksikonja improving random forest machine learning ecml proceeding j f b e al editor springer berlin variant random forest also useful contemplated method present invention example regression forest survival forest weighted population random forest modeling set sample used described diagnostic model built kde algorithm since analyte assay independent measurement variable circumstance known skilled art appropriate scale data adjust differing variance | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 8 | assay case biweight mad equivalent scaling would appropriate although case scaling would expected significant impact bootstrap layer top random forest used obtaining result discussed preferred embodiment present invention contemplated panel biomarkers cancer antigen ca swissprot accession number q epidermal growth factor receptor egfr swissprot accession number p b ca c reactive protein crp swissprot accession number p c ca crp egfr one ca crp egfr plus one ferritin swissprot accession number heavy chain p light chain p interleukin il swissprot accession number p tissue inhibitor metalloproteinases temp swissprot accession number p e one biomarker panel presented table ii fable ill f foregoing panel biomarkers ae plus one biomarkers following list previously included foregoing panel ae additional biomarkers identified empirically literature review alpha macroglobulin swissprot accession number p apolipoprotein apoa swissprot accession number p apolipoprotein apociii swissprot accession number p apolipoprotein h apoh swissprot accession number p beta microglobulin bm swissprot accession number p betacellulin swissprot accession number p c reactive protein crp swissprot accession number p cancer antigen ca swissprot accession number qbxj cancer antigen ca swissprot accession number q collagen type antibody creatine kinasemb ckmb swissprot accession number brain p muscle p c reactive protein crp swissprot accession number p connective tissue growth factor ctgf swissprot accession number p double stranded dna antibody dsdna ab enrage swissprot accession number p eotaxin cc motif chemokine smallinducible cytokine eosinophil chemotactic protein swissprot accession number p epidermal growth factor receptor egfr swissprot accession number p ferritin swissprot accession number heavy chain p light chain p folliclestimulating hormone fsh folliclestimulating hormone beta subunit fshbeta fshb follitropin beta chain follitropin subunit beta swissprot accession number p haptoglobin swissprot accession number p major epididymisspecific protein e epididymal secretory protein e putative protease inhibitor wap wap fourdisulfide core domain protein swissprot accession number q insulin swissprot accession number p insulinlike growth factor igf swissprot accession number p insulin like growth factor ii igfii somatomedina swissprot accession number p insulin factor vii swissprot accession number p interleukin il swissprot accession number p interleukin il swissprot accession number p interleukin il swissprot accession number p interleukin il swissprot accession number q leptin swissprot accession number p lymphotactin swissprot accession number p macrophagederived chemokine mdc swissprot accession number macrophage inhibotory factor swiss prot macrophage inflammatory protein alpha mipalpha swissprot accession number p macrophage migration inhibitory factor mif phenylpyruvate tautomerase glycosylationinhibiting factor gif swissprot accession number p myoglobin swissprot accession number p ostopontin bone sialoprotein secreted phosphoprotein spp urinary stone protein nephropontin uropontin swissprot accession number p pancreatic islet cell gad antibody prolactin swissprot accession number p stem cell factor scf swissprot accession number p tenascin c swissprot accession number p tissue inhibitor metalloproteinases timp swissprot accession number p tumor necrosis factoralpha tnfalpha swissprot accession number p tumor necrosis factor rii tnfrii swissprot accession number q von willebrand factor vwf swissprot accession number p biomarkers identified informative cancer reference cited specification using random forest analytical approach preferred seven biomarker panel identified high predictive value stage ovarian cancer includes apoai apociii ca crp egfr il tenascin course building selecting relatively accurate model stage cancer generated random forest using biomarkers sensitivity stage ovarian cancer ranged sensitivity also stage ii sensitive stage iiiiv overall specificity similarly preferred seven biomarker panel identified high predictive value stage ii includes bm ca ckmb crp ferritin il timp preferred model stage ii sensitivity specificity stage iii stage iv advanced ovarian cancer following biomarker panel identified ca crp ctgf egfr enrage ferritin haptoglobin igf il il insulin leptin lymphotactin mdc temp tnfalpha tnfrii vwf preferred model stage iiiiv sensitivity specificity preferred biomarker analyte panel detecting diagnosing monitoring ovarian cancer shown table ii table iii panel include ca crp egfr case ca table ii panel seven analytes selected preferred analytes displayed column numbered table iii another panel seven analytes selected preferred analytes displayed column numbered table ii additional biomarker panel ca x x x x x x x x x x x x x x x x x x x x crp x x x x x x x x x x x x x x x x x x x x egfr x x x x x x x x x x x x x x x x x x x x ca x x x x x x x x x x x x x x x x x x x haptoglobin serum amyloid p x x x apo ai x x il x x x x x x myoglobin x x x x x x x x x x x mip x x x x x x x x x x x x | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 9 | enrage ckmb vwf x x x leptin x x apo ciii x x x growth hormone x x x x x x il il x x x x x x x x myeloperoxidase x x vcam x x x table iii additional biomarker panel ca x x x x x x x x x x x x x x x x x x x x crp x x x x x x x x x x x x x x x x x x x x egfr x x x x x x x x x x x x x x x x x x x x ca x x x x x x x x x x x x x x x x x x x haptoglobin serum amyloid p x x x apo ai x x il x x x x x x myoglobin x x x x x x x x x x mip x x x x x x x x x x x x x x enrage ckmb x vwf x x x x leptin x x x apo ciii x x x x x x growth hormone il x x il myeloperoxidase x x x vcam insulin x ferritin x x x x x haptoglobin x preferred biomarker panel model stage ovarian cancer include ca crp egfr ca apoai apociii il il mipa tenascin c myoglobin b ca crp ca egfr myoglobin il apo ciii e ca crp egfr ca apo ciii mtpa myoglobin il il apo ai tenascin c vwf haptoglobin il optionally one following biomarkers may added biomarker panel disclosed text table extent panel already specifically identified therein vwf haptoglobin il igfi igfii prolactin ace asp resistin two preferred biomarkers described predictive value however adding one preferred marker analytical panel described herein may increase panel predictive value clinical purpose example adding one different biomarkers listed otherwise identified reference cited specification may also increase biomarker panel predictive value therefore expressly contemplated skilled artisan readily ass utility additional biomarkers contemplated additional biomarker appropriate addition set panel biomarkers disclosed claimed specification result decrease either sensitivity specificity without corresponding increase either sensitivity specificity without corresponding increase robustness biomarker panel overall sensitivity andor specificity least higher preferred preferably least higher preferably least higher practice method present invention appropriate cutoff level biomarker analytes must determined cancer sample comparison control sample discussed preferred least cancer sample benign sample including benign nonmalignant disease normal subject used purpose preferably case matched age sex gender larger sample set preferred person skilled art would measure level biomarker selected biomarker panel use algorithm preferably random forest compare level analytes cancer sample level analytes control sample way predictive profile prepared based informative cutoff relevant disease type use separate validation set sample preferred confirm cutoff value determined case control sample obtained obtaining consented anonymized sample clinical trial repository like screening study prostate lung colorectal ovarian cancerplco trial sponsored national cancer institute gynecologic oncology group sample obtained multiple site also preferred result analysis patient specimen using disclosed predictive biomarker panel may output benefit user diagnostician may otherwise displayed medium limited computer screen computer readable medium piece paper visible medium foregoing embodiment advantage invention set forth part preceding description example part apparent person skilled art description example may realized practicing invention disclosed herein example technique present invention readily applicable monitoring progression ovarian cancer individual evaluating specimen biological sample described repeating evaluation one later point time difference expression disregulation relevant biomarkers time indicative progression ovarian cancer individual responsiveness therapy reference patent journal article web page document identified patent application hereby incorporated reference entirety ovarian cancer biomarkersreferences ahmed n et al proteomicbased identification haptoglobin precursor novel circulating biomarker ovarian cancer br j cancer p ahmed n et al cellfree kda immunoreactive integrinlinked kinase novel marker ovarian carcinoma clin cancer re p ahmed n et al proteomic tracking serum protein isoforms screening biomarkers ovarian cancer proteomics p akcay et al significance | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 10 | omethylguaninedna methyltransferase glutathione stransferase activity serum patient malignant benign ovarian tumor eur j obstet gynecol reprod biol p h j et al profiling glycans serum discovery potential biomarkers ovarian cancer j proteome re p baron et al soluble epidermal growth factor receptor segfr corrected cancer antigen ca screening diagnostic test epithelial ovarian cancer cancer epidemiol biomarkers prev p baronhay et al elevated serum insulinlike growth factor binding protein prognostic marker patient ovarian cancer clin cancer re p bast r c jr et al prevention early detection ovarian cancer mission impossible recent result cancer re p benarie et al elevated serum alkaline phosphatase may enable early diagnosis ovarian cancer eur j obstet gynecol reprod biol p bergen h r rd et al discovery ovarian cancer biomarkers serum using nanolc electrospray ionization tof fticr mass spectrometry dis marker p bignotti e et al gene expression profile ovarian serous papillary carcinoma identification metastasisassociated gene j obstet gynecol p e boran n et al significance serum peritoneal fluid lactate dehydrogenase level ovarian cancer gynecol obstet invest p chen et al artificial neural network analysis surfaceenhanced laser desorptionionization mass spectrum serum protein pattern distinguishes colorectal cancer healthy population clin cancer re p chen et al application serum protein pattern model diagnosis colorectal cancer zhonghua zhong liu za zhi p chatterjee et al diagnostic marker ovarian cancer highthroughput antigen cloning detection array cancer re p clarke c h et al proteomics discovery urinary biomarkers early stage ovarian cancer annual meeting aacr conference los angeles convention center la ca conover c k r kalli method detecting ovarian neoplasia usa cox c j r g freedman h fritsche lactonfucopentaose iii activity serum patient ovarian carcinoma gynecol obstet invest p devine p l al serum mucin antigen casa msa tumor breast ovary lung pancreas bladder colon prostate blind trial patient cancer p dhokia b et al new immunoassay using monoclonal antibody iimfg hmfg together existing marker ca serological detection management epithelial ovarian cancer br j cancer p diefenbach c et al preoperative serum ykl marker detection prognosis endometrial cancer gynecol oncol p draghici chatterjee tainsky epitomics serum screening early detection cancer microarrays using complex panel tumor antigen expert rev mol diagn p einhorn n et al ca assay used conjunction ca tag assay discrimination malignant nonmalignant disease ovary acta oncol p erkanli et al application bayesian modeling autologous antibody response ovarian tumorassociated antigen cancer detection cancer re p fioretti p et al preoperative evaluation ca ca serum level patient ovarian mass eur j gynaecol oncol p fung e et al novel biomarkers aid differential diagnosis pelvic mass igcs conference santa monica calif fung e et al classification cancer type measuring variant host response protein using seldi serum assay int j cancer p funga e et al novel biomarkers predict survival patient ovarian cancer gadducci et al serum concentration tag antigen measured ca irma patient ovarian carcinoma preliminary data j nucl med allied sci p gorelik e et al multiplexed immunobeadbased cytokine profiling early detection ovarian cancer cancer epidemiol biomarkers prev p hellstrom et al mesothelin variant released tumor cell diagnostic marker cancer epidemiol biomarkers prev p ibanez de caceres et al tumor cellspecific brca rassfa hypermethylation serum plasma peritoneal fluid ovarian cancer patient cancer re p inoue et al sialyl lewisxi antigen patient gynecologic tumor obstet gynecol p inoue et al clinical value sialyl ssea antigen patient gynecologic tumor nippon sanka fujinka gakkai zasshi p kizawa kikuchi k kato diagnostic value biochemical tumor marker serum patient cancer ovary nippon sanka fujinka gakkai zasshi p knauf et al study nbok ca monoclonal antibody radioimmunoassay measuring serum antigen level ovarian cancer patient j obstet gynecol pt p kobayashi h terao kawashima clinical evaluation circulating serum sialyl tn antigen level patient epithelial ovarian cancer j clin uncut p koelbl ii et al comparative study mucinlike carcinomaassociated antigen mca ca ca cea patient ovarian cancer neoplasma p koivunen e et al cyst fluid ovarian cancer patient contains high concentration trypsinogen cancer re p kong f et al using | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 11 | proteomic approach identify new biomarkers detection monitoring ovarian cancer gynecol oncol p kozak k r et al identification biomarkers ovarian cancer using strong anionexchange proteinchips potential use diagnosis prognosis proc natl acad sci usa p kozak k r et al characterization serum biomarkers detection early stage ovarian cancer proteomics p lambeck j et al serum cytokine profiling diagnostic prognostic tool ovarian cancer potential role interleukin clin cancer re p le page c et gene profiling diagnostic marker il fgf complement ca serumbased marker epithelial ovarian cancer int j cancer p lim r et al neutrophil gelatinaseassociated lipocalin ngal earlyscreening biomarker ovarian cancer ngal associated epidermal growth factorinduced epitheliomesenchymal transition int j cancer p lin w et al plasma proteomic pattern biomarkers ovarian cancer int j gynecol cancer suppl p lokshin enhanced diagnostic multimarker serological profiling usa lokshin e et al circulating il antiil autoantibody patient ovarian cancer gynecol oncol p lopez f et al novel highthroughput workflow discovery identification serum carrier proteinbound peptide biomarker candidate ovarian cancer sample clin chem p malki et al expression biological role prostaglandin synthasesox pathway human ovarian cancer cell cancer lett massi g b et al significance measurement several oncofetal antigen diagnosis management epithelial ovarian tumor eur j gynaecol oncol p meden h et al elevated serum level cerbb oncogene product ovarian cancer patient pregnancy j cancer re clin oncol p mehta et al biomarker amplification serum carrier protein binding dis marker p meinholdheerlein et al integrated clinicalgenomics approach identifies candidate multianalyte blood test serous ovarian carcinoma clin cancer re pt p miszczakzaborska e et al activity thymidine phosphorylase new ovarian tumor marker gynecol oncol p moore l e et al evaluation apolipoprotein posttranslationally modified form transthyretin biomarkers ovarian cancer detection independent study population cancer epidemic biomarkers prev p mor g et al serum protein marker early detection ovarian cancer proc natl acad sci usa p moscova j marsh r c baxter protein chip discovery secreted protein regulated phosphatidylinositol kinase pathway ovarian cancer cell line cancer re p nakae et al preoperative plasma osteopontin level biomarker complementary carbohydrate antigen predicting ovarian cancer j obstet gynaecol re p nozawa et al galactosyltransferase isozyme ii gtii new tumor marker ovarian cancersespecially clear cell carcinoma nippon sanka fujinka gakkai zasshi p nozawa et al clinical significance galactosyltransferase associated tumor gat new tumor marker ovarian cancerwith special reference discrimination ovarian cancer endometriosis gan kagaku ryoho p paliouras c borgono e p diamandis human tissue kallikreins cancer biomarker family cancer lett p paulick r et al clinical significance different serum tumor marker gynecological malignancy cancer detect prev p plebani et al combined use urinary ugp serum ca diagnosis gynecological cancer anticancer re b p robertson e pruysers jobling inhibin diagnostic marker ovarian cancer cancer lett p rzymski p et al evaluation serum sicam amd ca patient ovarian tumorspreliminary report ginekol poi p sawada et al immunosuppressive acidic protein patient gynecologic cancer cancer p scambia g et al ca tumor marker gynecological malignancy gynecol oncol p scambia g et al measurement monoclonalantibodydefined antigen k serum patient ovarian cancer anticancer re p scholler n et al beadbased elisa validation ovarian cancer early detection marker clin cancer re pt p l l davis l hazen plasmalogens new class biomarkers ovarian cancer detection th asms annual conference indianapolis ind simon et al evaluation novel serum marker bh spondin dcr diagnosis early detection ovarian cancer gynecol oncol simon et al bh novel membranebound protein candidate serum tissue biomarker ovarian cancer cancer re p simon r development evaluation therapeutically relevant predictive classifier using gene expression profiling j natl cancer inst p skate j et al preoperative sensitivity specificity earlystage ovarian cancer combining cancer antigen caii ca ca macrophage colonystimulating factor using mixture multivariate normal distribution j clin oncol p skate j et al pooling case specimen create standard serum set screening cancer biomarkers cancer epidemiol biomarkers prev p sun z et al protein chip system parallel analysis multitumor marker application cancer detection anticancer re c p ta f et al value | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 12 | serum bcl level advanced epithelial ovarian cancer med oncol p taylor c gerceltaylor gall expression shedding cd variant isoforms patient gynecologic malignancy j soc gynecol investig p tosner j j krejsek b louda serum prealbumin transferrin alphaacid glycoprotein patient gynecological carcinoma neoplasma p tsigkou et al total inhibin potential serum marker epithelial ovarian cancer j clin endochrin metal tsukishiro et al preoperative serum thrombopoietin level higher patient ovarian cancer benign cyst eur j obstet gynecol reprod biol vlahou et al diagnosis ovarian cancer using decision tree classification mass spectral data j biomed biotechnol p woongshick et al identification hemoglobinalpha beta subunit potential serum biomarkers diagnosis prognosis ovarian cancer cancer sci p wu p et al selditof m profiling plasma protein ovarian cancer taiwan j obstet gynecol p xu et al lysophosphatidic acid potential biomarker ovarian gynecologic cancer jama p yabushita h et al combination assay ca tpa iap cea ferritin serum ovarian cancer gynecol oncol p ye b et al proteomicbased discovery characterization glycosylated eosinophilderived neurotoxin coohterminal osteopontin fragment ovarian cancer urine clin cancer re p yu j k et al integrated approach utilizing proteomics bioinformatics detect ovarian cancer j zhejiang univ sci b p yurkovetsky z r serum multimarker assay early detection ovarian cancer th international molecular medicine triconference moscone norht convention center san fransisco calif zhang h et al biomarker discovery ovarian cancer using selditofms gynecol oncol p zhang z et al three biomarkers identified serum proteomic analysis detection early stage ovarian cancer cancer re p zhao c et al circulating haptoglobin independent prognostic factor serum patient epithelial ovarian cancer neoplasia p claim invention claimed article manufacture comprising set reagent measure level panel biomarkers specimen wherein panel biomarkers comprise ca apo fsh measurable fragment wherein set reagent bound solid support specifically bind said biomarkers set reagent claim wherein reagent binding molecule set reagent claim wherein binding molecule antibody test kit comprising set reagent claim multianalyte panel assay comprising set reagent claim method predicting likelihood cancer subject comprising detecting level biomarkers specimen using set reagent claim wherein change level biomarkers compared control group patient cancer predictive cancer subject method claim wherein cancer ovarian cancer method claim wherein change relative level biomarkers determined method claim wherein specimen selected group consisting blood serum plasma lymph cerebrospinal fluid ascites urine tissue biopsy method claim wherein ovarian cancer selected group consisting serous endometrioid mucinous clear cell cancer method claim wherein prediction ovarian cancer includes stage selected group consisting stage ia ib ic ii iii iv tumor method claim comprising creating report relative level biomarkers method claim wherein report includes prediction presence absence ovarian cancer subject stratified risk ovarian cancer subject optionally stage cancer method claim wherein sample taken subject selected group consisting subject symptomatic ovarian cancer subject high risk ovarian cancer method claim wherein method sensitivity least percent specificity least percent method claim wherein sensitivity specificity determined population woman symptomatic ovarian cancer ovarian cancer compared control group woman symptomatic ovarian cancer ovarian cancer method ass therapeutic efficacy cancer treatment comprising comparing biomarker profile specimen taken subject treatment course treatment set reagent according claim wherein change biomarker profile time toward noncancer profile stable profile interpreted efficacy method determining whether subject potentially developing cancer comprising comparing biomarker profile specimen taken subject two point time set reagent according claim wherein change biomarker profile toward cancer profile interpreted progression toward developing cancer u predictive biomarkers ovarian cancer active usb en priority application application number priority date filing date title u usb en predictive biomarkers ovarian cancer u | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
"cs.CL"
] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 13 | usa en predictive biomarkers ovarian cancer application claiming priority application number priority date filing date title usp usp u usb en predictive marker ovarian cancer u usb en predictive marker ovarian cancer u usb en predictive biomarkers ovarian cancer u usb en predictive biomarkers ovarian cancer related parent application application number title priority date filing date u continuation usb en predictive biomarkers ovarian cancer related child application application number title priority date filing date u continuation usa en predictive biomarkers ovarian cancer publication publication number publication date usa usa en usb true usb en family id family application application number title priority date filing date u active usb en predictive marker ovarian cancer u active usb en predictive marker ovarian cancer u active usb en predictive biomarkers ovarian cancer u active usb en predictive biomarkers ovarian cancer u pending usa en predictive biomarkers ovarian cancer family application application number title priority date filing date u active usb en predictive marker ovarian cancer u active usb en predictive marker ovarian cancer u active usb en predictive biomarkers ovarian cancer family application application number title priority date filing date u pending usa en predictive biomarkers ovarian cancer country status country link u usb en ep epa en jp jpa en kr krb en cn cnb en br brpia en ca cac en mya en sg sga en wo woa en family citing family cited examiner cited third party publication number priority date publication date assignee title gbd en medical re council compartmentalised combinatorial chemistry gbd en medical re council selection compartmentalised screening usa en medical research council compartmentalised combinatorial chemistry microfluidic control usa en medical research council harvard university compartmentalised screening microfluidic control usb en medical research council harvard university vitro evolution microfluidic system jpa en microfluidic device method use nanoreactor formation control woa en raindance technology inc microfluidic device method use thereof usb en raindance technology inc system handling microfludic droplet woa en president fellow harvard college fluorocarbon emulsion stabilizing surfactant usb en brandeis university manipulation fluid reaction microfluidic system aua en immunovia ab protein signaturemarkers detection adenocarcinoma woa en brandeis university manipulation fluid fluid component reaction microfluidic system usb en wallace b haigh reagent kit early diagnosis kidney disease jpa en fujifilm corp method detecting ovarian cancer method suppressing epa en correlogic system inc predictive marker ovarian cancer epa en adnagen ag method kit diagnosing controlling treatment ovarian cancer epa en healthlinx ltd assay detect gynecological condition woa en raindance technology inc droplet library epb en raindance technology inc manipulation microfluidic droplet cnb en kind new tumor marker cnb en tumor marker epa en universite de strasbourg labelled silicabased nanomaterial enhanced property us thereof est en astute medical inc method composition diagnosis prognosis kidney injury kidney failure epb en biorad laboratory inc method reducing exchange molecule droplet usa en christine kuslich dectection gastrointestinal disorder usb en raindance technology inc digital analyte analysis usb en raindance technology inc digital analyte analysis jpb en digital specimen analysis usb en biorad laboratory inc digital analyte analysis nza en astute medical inc method composition diagnosis prognosis renal injury renal failure caa en caris life science luxembourg holding sarl biomarkers theranostics bra en caris life science luxembourg holding circulating biomarkers disease woa en raindance technology inc sandwich assay droplet epa en vermillion inc prognostic biomarkers patient ovarian cancer cna en method determining antiproteinase antibody igg intravenous gamma globulin reagent device epa en biorad laboratory inc method forming mixed droplet epb en biorad laboratory inc composition method molecular labeling aub en aspira woman health inc biomarker panel diagnostic method test kit ovarian cancer cnb en reagent diagnosis screening ovarian cancer epa en biorad laboratory inc microfluidic apparatus identifying component chemical reaction usb en raindance technology inc sample multiplexing woa en brigham woman hospital inc system method integration mobile device imaging microchip elisa usb en raindance technology inc manipulating droplet size usb en astute medical inc method diagnosis prognosis renal injury renal failure using insulinlike growth factorbinding protein metalloproteinase inhibitor woa en quest diagnostics investment incorporated assay method diagnosis ovarian cancer epa en raindance technology inc molecular diagnostic screening assay cnb en kit detection assisted detection tuberculous | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 14 | pleurisy woa en raindance technology inc digital analyte analysis usb en gemvax kael co ltd composition preventing treating rheumatoid arthritis cnb en antiinflammatory peptide composition comprising woa en georgia regent university biomarkers ovarian cancer woa en cellpenetrating peptide conjugate comprising composition comprising est en sphingotec gmbh method predict risk contracting breast cancer diagnosing cancer female subject ptt en astute medical inc method composition diagnosis prognosis renal injury renal failure est en gemvax kael co ltd composition treatment prevention ischemic injury woa en raindance technology inc digital analyte analysis rua en cancer treatment method krb en biological marker useful cancer immunotherapy est en gemvax kael co ltd regulator hormonal secretion composition contains procedure control hormonal secretion use usa en tsinghua university tumor biomarker cna en antibody chip kit joint detection early ovarian cancer marker aub en adelaide research innovation pty ltd autoantibody biomarkers ovarian cancer epb en gemvax kael co ltd composition treating preventing benign prostatic hyperplasia gbd en immunovia ab method array use thereof krb en peptide angiogenesis inhibitory activity composition containing usb en raindance technology inc distinguishing rare variation nucleic acid sequence sample krb en composition treating prostate cancer epb en biorad laboratory inc method detection latent retrovirus epb en samsung electronics co ltd il predicting monitoring efficacy cmet inhibitor krb en use dianhydrogalactitol analog derivative thereof treat nonsmallcell carcinoma lung ovarian cancer jpb en peptide fibrosis inhibitory activity composition containing woa en composition organ tissue cell transplantation kit transplantation method krb en peptide treating ophthalmopathy composition comprising est en gemvax kael co ltd peptide prevent hearing loss composition comprises woa en aelan cell technology inc method device production delivery beneficial factor stem cell jpb en peptide antiviral activity composition containing usb en biorad laboratory inc nucleic acid library generation method composition usb en gem vax kael co ltd peptide effect increasing telomerase activity extending telomere composition containing usa en eisai inc prognosis serous ovarian cancer using biomarkers usb en astute medical inc management acute kidney injury using insulinlike growth factorbinding protein tissue inhibitor metalloproteinase cna en primer set detection method detecting ovarian cancer usa en brigham woman hospital inc system method protein corona sensor array early detection disease jpb en eye japan biological information evaluation system usb en purdue research foundation system method sample analysis using swab cna en identification use glycopeptides biomarkers diagnosis therapy monitoring krb en biomarkers diagnosing ovarian cancer us thereof aua en caris mpi inc nextgeneration molecular profiling cnb en colorectal cancer diagnosis marker colorectal cancer detection product application thereof cna en transthyretin inhibiting application neonate tumour blood vessel cnb en bovine tuberculosis diagnosis marker application thereof woa en f hoffmannla roche ag sa blood biomarker noninvasive diagnosis endometriosis caa en icahn school medicine mount sinai system method detecting disease condition woa en method forming biomarker panel diagnosing ovarian cancer biomarker panel diagnosing ovarian cancer ila en aspira woman health inc composition ovarian cancer assessment improved specificity sensitivity cnb en spondin ca combined used early ovarian cancer biomarker kit gbd en immunovia ab method array us thereof cnb en wnta ca combined early ovarian cancer biomarker kit caa en johannes fahrmann method detection treatment ovarian cancer citation cited examiner cited third party publication number priority date publication date assignee title usa en stephen richard g pattern recognition method apparatus usa en chemetron corporation programmed thermal degradationmass spectrometry analysis method facilitating identification biological specimen usa en united state america represented administrator national aeronautics space administration automated clinical system chromosome analysis gba en eric james sjoberg pyrolysis mass spectrometer disease diagnosis aid usa en holland john h adaptive computing system capable learning discovery usa en regent university michigan method controlling classifier system usa en koza john r nonlinear genetic algorithm solving problem finding fit composition function woa en | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 15 | becton dickinson company gravitational attractor engine adaptively autoclustering ndimensional data stream usa en wayne state university method analyzing organic sample woa en svetlana borisovna shapiro method computer urinodiagnostics kidney disease usa en tafas triantafillos p cytological screening method usa en florida institute technology determination concentration biological substance using raman spectroscopy artificial neural network discriminator usa en nanogen molecular biological diagnostic system including electrode usa en apple computer inc vector quantization usa en loctite corporation method preparing fiberresin composite usa en kaufmann peter selective differentiating diagnostic process based broad data base usa en biofield corp method apparatus disease injury bodily condition screening sensing woa en interactiva biotechnologie gmbh broad specificity affinity array qualitative approach complex sample discrimination usa en hewlett packard company integrated nucleic acid analysis system malditof m usa en baylor college medicine method apparatus desorption ionization analytes usa en horus therapeutic inc computer assisted method diagnosing disease usa en heseltine gary l method apparatus diagnosis colorectal cancer usa en boehringer mannheim gmbh method apparatus determining analytical data concerning inside scattering matrix usa en neuralmed inc computerbased neural network system method medical diagnosis interpretation usa en board trustee operating michigan state university method system detection biological material using fractal dimension usa en advanced research techology institute hybrid ion mobility mass spectrometer woa en oxford glycosciences uk ltd method composition diagnosis hepatoma usa en university wale aberystwyth composition analysis woa en oxford glycosciences uk ltd method composition diagnosis rheumatoid arthritis usa en sapient health network intelligent query system automatically indexing information database automatically categorizing user woa en ikonisys inc method apparatus computer controlled rare cell including fetal cell based diagnosis usa en mesosystems technology inc apparatus method lysing bacterial spore facilitate identification usa en applied spectral imaging ltd method cancer cell detection usa en applied spectral imaging ltd situ method analyzing cell usa en university tulsa prediction prostate cancer progression analysis selected predictive parameter usa en medison co ltd realtime biological signal monitoring system using radio communication network usa en american heuristic corporation adaptive temporal correlation network woa en government united state america represented secretary department health human service national institute health lcm laser capture microdissection cellular protein analysis usa en incyte pharmaceutical inc comparative gene transcript analysis woa en oxford glycosciences uk ltd protein diagnosis treatment breast cancer usa en barnhill technology llc enhancing knowledge discovery using multiple support vector machine woa en affymetrix inc method cluster analysis gene expression profile usb en ciphergen biosystems inc use retentate chromatography generate difference map woa en barnhill technology llc method device identifying pattern biological pattern woa en biowulf technology llc method device identifying pattern biological system usb en cyrano science inc handheld sensing apparatus usb en dimensional pharmaceutical inc method system computer program product representing similaritydissimilarity chemical compound usb en david sheehan prescriptioncontrolled data collection system method woa en mosaiques diagnostics therapeutic ag method device qualitative andor quantitative analysis protein andor peptide pattern liquid sample derived human animal body usb en eastman kodak company method comparison similar sample liquid chromatographymass spectrometry woa en general hospital corporation compound method fluorescently labeling nucleic acid usa en otworth michael j method apparatus processing remotely collected electronic information characterizing property biological entity woa en biowulf technology llc method identifying pattern biological system us thereof woa en ciphergen biosystems inc improved method protein identification characterization sequencing tandem mass spectrometry woa en synx pharma inc diagnosis physiological condition proteomic characterization usb en queen university kingston coincidence detection method product apparatus usa en gavin edward j method analyzing mass spectrum usa en ciphergen biosystems inc method correlating gene expression profile protein expression profile woa en ciphergen biosystems inc method analyzing mass spectrum usa en ciphergen biosystems inc biomolecule characterization using mass spectrometry affinity tag usb en sequenom inc infrared matrixassisted laser desorptionionization mass spectrometric analysis macromolecule usb en dimensional pharmaceutical inc method system computer program product nonlinear mapping multidimensional data usa en hubert koster dna diagnostics based mass spectrometry usa en jan van der greef method system profiling biological system woa en boditech inc lateral flow quantitative assay method strip laserinduced fluoerescence detection device therefor usb en accenture llp abstraction factory base service pattern environment usb en california institute technology method remote characterization odor usb en esperion therapeutic inc fourier transform mass spectrometry complex biological sample usa en hitt ben quality assurancequality control electrospray ionization process usa en masashi takahashi | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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] | null | cs.CL | 20191002 | 20200301 | [
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1910.01108 | 16 | data managing system xray computed tomographic apparatus xray computed tomograhic system woa en alcohol monitoring system llc bioinformation sensor monitoring system method usa en schwamm lee h system process diagnostic arrangement establishing monitoring medication dos patient usa en john hopkins university use biomarkers detecting ovarian cancer usa en lokshin anna e multifactorial assay cancer detection usb en correlogic system inc process discriminating biological state based hidden pattern biological data usa en tzonghao chen method diagnosing biological state use centralized adaptive model remote sample processing usa en yale university identification cancer protein biomarkers using proteomic technique woa en meddynamics ltd system method administration online healthcare usa en hitt ben multiple highresolution serum proteomic feature ovarian cancer detection usb en sionex corporation system differential ion mobility analysis usb en correlogic system inc heuristic method classification usa en aviaradx inc breast cancer progression signature usa en hitt ben identification bacteria spore usa en burgess nicola protein involved ovarian cancer usa en university pittsburgh commonwealth system higher education enhanced diagnostic multimarker serological profiling usa en vermillion inc prognostic biomarkers patient ovarian cancer usa en ciphergen biosystems inc biomarkers ovarian cancer b microglobulin usb en vermillion inc predictive marker ovarian cancer family cite family cited examiner cited third party publication number priority date publication date assignee title usa en yale university method detecting onset progression regression gynecologic cancer jpha en ind technol re inst acute myocardial infarction diagnosis kit usa en chondrogene limited method detection cancer related gene transcript blood aua en spectral diagnostics inc preparation sphere diagnostic test usa en robertson john forsyth russell cancer detection method reagent woa en virginia mason research center antigen panel method using cna en method detecting screening andor monitoring cancer individual usa en mount sinai hospital multiple marker assay detection ovarian cancer woa en john hopkins university biomarkers ovarian cancer epa en rule based medicine inc universal shotgun assay cac en ciphergen biosystems inc biomarkers ovarian cancer endometrial cancer cnb en biomarkers ovarian cancer ctap related protein cac en ciphergen biosystems inc biomarkers ovarian cancer usa en rulesbased medicine inc method kit diagnosis acute coronary syndrome est en valchum sec procedure diagnosis ovarian cancer jpb en chemical treatment cartridge method use thereof ep epa patentepaen notactive withdrawn mypia patentmyaen unknown sg sga patentsgaen unknown cn cna patentcnben notactive expired fee related jp jpa patentjpaen active pending ep epa patentepaen notactive withdrawn wo pctus patentwoaen active application filing br brpia patentbrpiaen notactive application discontinuation ca caa patentcacen active active kr kra patentkrben notactive ip right cessation u u patentusben active active kr kra patentkraen notactive application discontinuation u u patentusben active active u u patentusben active active u u patentusben active active u u patentusaen active pending patent citation cited examiner cited third party publication number priority date publication date assignee title usa en stephen richard g pattern recognition method apparatus usa en chemetron corporation programmed thermal degradationmass spectrometry analysis method facilitating identification biological specimen usa en chemetron corporation method generate correlative data various product thermal degradation biological specimen usa en united state america represented administrator national aeronautics space administration automated clinical system chromosome analysis usa en holland john h adaptive computing system capable learning discovery gba en eric james sjoberg pyrolysis mass spectrometer disease diagnosis aid usa en regent university michigan method controlling classifier system usa en biofield corp method apparatus disease injury bodily condition screening sensing usa en koza john r nonlinear genetic algorithm solving problem finding fit composition function usa en wayne state university method analyzing organic sample woa en becton dickinson company gravitational attractor engine adaptively autoclustering ndimensional data stream woa en svetlana borisovna shapiro method computer urinodiagnostics kidney disease usa en incyte pharmaceutical inc comparative gene transcript analysis usa en apple computer inc vector quantization usa en heseltine gary l method apparatus diagnosis colorectal cancer usa en loctite corporation method preparing fiberresin composite usa en baylor college medicine method apparatus desorption ionization analytes usa en applied spectral imaging ltd method cancer cell detection usa en tafas triantafillos p cytological screening method usa en nanogen molecular biological diagnostic system including electrode usa en florida institute technology determination concentration biological substance using raman spectroscopy artificial neural network discriminator usa en university tulsa prediction prostate cancer progression analysis selected predictive parameter usa en horus | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 17 | therapeutic inc computer assisted method diagnosing disease usb en horus therapeutic inc computer assisted method diagnosing disease usa en board trustee operating michigan state university method system detection biological material using fractal dimension usa en university wale aberystwyth composition analysis usa en medison co ltd realtime biological signal monitoring system using radio communication network usa en hewlett packard company integrated nucleic acid analysis system malditof m usa en kaufmann peter selective differentiating diagnostic process based broad data base usa en boehringer mannheim gmbh method apparatus determining analytical data concerning inside scattering matrix usa en applied spectral imaging ltd situ method analyzing cell woa en interactiva biotechnologie gmbh broad specificity affinity array qualitative approach complex sample discrimination usa en neuralmed inc computerbased neural network system method medical diagnosis interpretation usb en dimensional pharmaceutical inc method system computer program product representing similaritydissimilarity chemical compound usb en dimensional pharmaceutical inc method system computer program product nonlinear mapping multidimensional data usa en hubert koster dna diagnostics based mass spectrometry usb en queen university kingston coincidence detection method product apparatus usa en advanced research techology institute hybrid ion mobility mass spectrometer usb en ciphergen biosystems inc retentate chromatography protein chip array application biology medicine usb en ciphergen biosystems inc use retentate chromatography generate difference map usa en american heuristic corporation adaptive temporal correlation network usa en sapient health network intelligent query system automatically indexing information database automatically categorizing user woa en oxford glycosciences uk ltd method composition diagnosis hepatoma woa en oxford glycosciences uk ltd method composition diagnosis rheumatoid arthritis usb en cyrano science inc handheld sensing apparatus usa en barnhill technology llc enhancing knowledge discovery using multiple support vector machine usa en barnhill technology llc enhancing knowledge discovery using support vector machine distributed network environment usb en biowulf technology llc enhancing knowledge discovery using multiple support vector machine usb en sequenom inc infrared matrixassisted laser desorptionionization mass spectrometric analysis macromolecule woa en ikonisys inc method apparatus computer controlled rare cell including fetal cell based diagnosis usb en david sheehan prescriptioncontrolled data collection system method usa en mesosystems technology inc apparatus method lysing bacterial spore facilitate identification woa en government united state america represented secretary department health human service national institute health lcm laser capture microdissection cellular protein analysis woa en oxford glycosciences uk ltd protein diagnosis treatment breast cancer usb en california institute technology method remote characterization odor usb en sionex corporation system differential ion mobility analysis usb en eastman kodak company method comparison similar sample liquid chromatographymass spectrometry usb en accenture llp abstraction factory base service pattern environment woa en affymetrix inc method cluster analysis gene expression profile woa en barnhill technology llc method device identifying pattern biological pattern woa en biowulf technology llc method device identifying pattern biological system woa en mosaiques diagnostics therapeutic ag method device qualitative andor quantitative analysis protein andor peptide pattern liquid sample derived human animal body usb en correlogic system inc heuristic method classification usb en correlogic system inc heuristic method classification usa en ben hitt heuristic method classification woa en general hospital corporation compound method fluorescently labeling nucleic acid usb en esperion therapeutic inc fourier transform mass spectrometry complex biological sample usa en otworth michael j method apparatus processing remotely collected electronic information characterizing property biological entity usa en hitt ben process discriminating biological state based hidden pattern biological data usb en correlogic system inc process discriminating biological state based hidden pattern biological data woa en ciphergen biosystems inc method analyzing mass spectrum usb en ciphergen biosystems inc method analyzing mass spectrum usb en ciphergen biosystems inc method analyzing mass spectrum woa en biowulf technology llc method identifying pattern biological system us thereof woa en ciphergen biosystems inc improved method protein identification characterization sequencing tandem mass spectrometry usa en ciphergen biosystems inc method correlating gene expression profile protein expression profile usa en ciphergen biosystems inc biomolecule characterization using mass spectrometry affinity tag woa en synx pharma inc diagnosis physiological condition proteomic characterization usa en schwamm lee h system process diagnostic arrangement establishing monitoring medication dos patient usa en jan van der greef method system profiling biological system usa en aviaradx inc breast cancer progression signature woa en boditech inc lateral flow quantitative assay method strip laserinduced fluoerescence detection device therefor usa en gavin edward j method analyzing mass spectrum usb en correlogic system inc quality assurancequality control high throughput bioassay process usb en | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1910.01108 | 18 | correlogic system inc quality assurance highthroughput bioassay method usa en hitt ben quality assurancequality control electrospray ionization process usa en john hopkins university use biomarkers detecting ovarian cancer usa en masashi takahashi data managing system xray computed tomographic apparatus xray computed tomograhic system woa en alcohol monitoring system llc bioinformation sensor monitoring system method usa en hitt ben multiple highresolution serum proteomic feature ovarian cancer detection usa en university pittsburgh commonwealth system higher education enhanced diagnostic multimarker serological profiling usa en lokshin anna e multifactorial assay cancer detection usa en burgess nicola protein involved ovarian cancer usa en tzonghao chen method diagnosing biological state use centralized adaptive model remote sample processing usa en yale university identification cancer protein biomarkers using proteomic technique woa en meddynamics ltd system method administration online healthcare usa en hitt ben identification bacteria spore usa en ciphergen biosystems inc biomarkers ovarian cancer b microglobulin usa en vermillion inc prognostic biomarkers patient ovarian cancer usb en vermillion inc predictive marker ovarian cancer usb en vermillion inc predictive marker ovarian cancer nonpatent citation cited examiner cited third party title benaire et al elevated serum alkaline phosphatase may enable early diagnosis ovarian cancer pubmed european journal obstetrics gynecology reproductive biology vol sep page gaducci et al serum concentration tag antigen measured ca irma patient ovarian carcinoma preliminary data pubmed j nuci med allied sci vol janmar adam bl et al serum protein fingerpriting coupled pattern matching algorithm disctinguishes prostate cancer benign prostate hyperplasia healthy men cancer research jul pp vol ae lokshin et al circulating il antiil autoantibody patient ovarian cancer pubmed gynecology oncology vol aug page ahmed n et al proteomic tracking serum protein isoforms screening biomarkers ovarian cancer pubmed proteomics vol nov page ahmed nuzhat et al cellfree kda immunoreactive integrinlinked kinase novel marker ovarian carcinoma clinical cancer research vol apr pp ahmed nuzhat et al proteomicbased identification haptoglobin precursor novel circulating biomarker ovarian cancer british journal cancer vol pp akay et al significance methylguaninedna methyltransferase glutathione stransferase activity era patient malignant benign ovarian tumor european journal obstet gynecol reprod biol vol mar pp al mehta et al biomarker amplification serum carrier protein binding pubmed dis marker vol page alaiya aa et al classification human ovarian tumor using multivariate data analysis polypeptide expression pattern int j cancer pp vol hyun j et al profiling glycans serum discovery potential biomarkers ovarian cancer journal proteome research american chemical society vol pp ashfaq r et al evaluation papnet tm system rescreening negative cervical smear diagnostic cytophathology pp vol astion ml et al application backpropagation neural network problem pathology laboratory medicine arch pathol lab med oct pp vol atkinson en et al statistical tchniques diagnosing cin using fluorescence spectroscopysvd cart journal cellular biochemistry supplement pp babaian rj et al performance neural network detecting prostate cancer prostatespecific antigen reflex range ngml urology pp vol babcock b et al ovarian breast sytotoxic lymphocyte recognize peptide amino enhancer split protein notch complex molecular immunology pp vol baileykellogg c et al reducing mass degeneracy sar m stable isotopic labeling journal computational biology pp vol balteskard l et al medical diagnosis internet age lancet dec siv vol baron et al soluble epidermal growth factor receptor segfr corrected cancer antigen ca screening diagnostic test epithelial ovarian cancer cancer epidemiol biomarkers prey p baronhay sally et al elevated serum insulinlike growth factor binding protein prognostic mmarker patient ovarian cancer clinical cancer research mar pp bast jr rc et al prevention early detection ovarian cancer mission impossible pubmed recent result cancer research vol page bast rc status tumor marker ovarian cancer screening journal clinical oncology vol may pp belic et al neural network methodology mass spectrum recognition vacuum pp vol belic neural network methodology mass spectrum recognition pp additional detail unknown bellamy jec medical diagnosis diagnostic space fuzzy system javma feb pp vol berikov vb et al regression tree analysis mutational spectrum nucleotide sequence bioimformatics pp vol no bignotti eliana et al gene expression profile ovarian serous papillary carcinoma identification metastasisassociated gene research oncology american journal obstetrics gynecology mar pp e bittl ja confusion clarity direct thrombin inhibitor patient heparininduced thrombocytopenia cath cardio intervention pp vol boran n et al significance serum peritoneal fluid lactate dehydrogenase level | 1910.01108 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1910.01108 | [
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1710.06481 | 0 | ovarian cancer pubmed gynecol obstet invest vol page breiman l et al classification regression tree boca raton chapman hallcrc pp ch medical diagnosis prognosis brown mp et al knowledgebased analysis microarray gene expression data using support vector machine pnas jan pp vol cairn ay et al towards automated prescreening breast xrays alistair gain department mathematics computer science university dundee pp canadian office action corresponding canadian application dated jan page caprioli rm et al molecular imagine biological sample localization peptide protein using malditof m analytical chemistry pp vol chace dh et al laboratory integration utilization tandem mass spectrometry neonatal screening model clinical mass spectrometry next millennium acta paediatr suppl pp chang et et al using genetic algorithm select create feature pattern classification ijcnn international joint conference neural network jan pp iii iii chatterjee madhumita et al diagnostic marker ovarian cancer highthroughput antigen cloning detection array research article cancer research vo jan pp chen et al application serum protein pattern model diagnosis colorectal cancer zhonghua zhong liu za zhi jul chen yiding et al artificial neural network analysis surfaceenhanced laser desorptionionization mass spectrum protein pattern distinguishes colorectal cancer healthy population clinical cancer research vol dec pp christiaens b et al fully automated method liquid chromatographictandem mass spectrometric determination cyproterone acctate human plasma using restricted access material online sample cleanup journal chromatography pp vol chu c rubin sc screening ovarian cancer general population baillieres best practice research clinical obstetrics andgynaecology bailliere tindall london gb vol april gb page xp issn doi jbpobgyn chu et al screening ovarian cancer general population billieres best practice research clinical obstetrics gynecology bailliere tindall london vol xp apr pp chun j et al longterm identification streptomycetes using pyrolysis mass spectrometry artificial neural network zbl nalt pp vol cicchetti dv neural network diagnosis clinical laboratory state art clinical chemistry pp vol ciphergen european update pp vol cj cox et al lactonfucopentaose iii activity serum patient ovarian carcinoma pubmed gynecology obstetrics invest vol page clarke c h et al proteomics discovery urinary biomarkers early stage ovarian cancer annual meeting aacr conference los angeles convention center la calif claydon et al rapid idenitifcation intact microorganism using mass spectrometry abstract page online retrieved feb claydon et al rapid idenitifcation intact microorganism using mass spectrometry nature biotech nov pp vol conrad tp et al highresolution serum proteomic feature ovarian cancer detection endocrinerelated cancer pp vol crawford lr et al computer method analytical mass spectrometry empirical identification molecular class analytical chemistry aug pp vol c diefenbach et al preoperative serum ykl marker detection prognosis endometrial cancer pubmed gynecology oncology vol feb page curry et al msnet neural network classifies mass spectrum standford university oct tetrahedron computer methodology pp dd taylor et al expression shedding cd variant isoforms patient gynecologic malignancy pubmed j soc gynecol investig vol sepoct page de brabandere vi et al isotope dilutionliquid chromatographyelectrospray ionizationtandem mass spectrometry determindation serum thyroxine potential reference method rapid communication mass spectrometry pp vol de caceres inmaculada et al tumor cellspecific brca rassfia hypermethylation serum plasma peritoneal fluid ovarian cancer patient cancer research vol sep pp devine pl et al serum mucin antigen casa msa tumor breast ovary lung pancreas bladder colon prostate blind trial patient pubmed cancer vol sep page dhar v et al seven method trasnforming corporate data business intelligence upper saddle river nj prentice hall pp dhokia b et al new immunoassy using monoclonal antibody hmfg hmfg together existing marker ca serological detection management epithelial ovarian cancer macmillian press ltd br j cancer vol pp dm robertson et al inhibin diagnostic marker ovarian cancer pubmed cancer letter vol apr page draghici et al epitomics serum screening early detection cancer microarrays using complex panel tumor antigen pubmed expert rev mol diagn vol sep page dudoit et al comparison discrimination method classification tumor using gene expression data mathematical science research institute berkeley ca technical report jun pp dzeroski et al diterpene structure elucidation c nmrspectra machine learning boston kluwer academic publisher intelligent data analysis medicine pharmacology pp e miszczakzaborska et al activity thymidine phosphorylas new ovarian tumor marker pubmed gynecology oncology vol jul page eghbaldar et al identification structural feature mass spectrometry using neural network approach application trimethylsilyl derivative used medical diagnosis j chem inf comput sci pp | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 1 | vol einhorn n et al ca assay used conjunction ca tag assay discrimination maliganant nonmalignant disease ovary pubmed ada oncol vol page english translation written opinion corresponding brazilian application pi dated jul page erkanli al et al application bayesian modeling autologous antibody response ovarian tumorassociated antigen cancer detection research article cancer research vol feb pp et fung et al classification cancer type measuring variant host response protein using seldi serum assay pubmed int j cancer vol jul page extended search report response european patent application filed mar page f kong et al using proteomic approach identify new biomarkers detection monitoring ovarian sancer pubmed gynecology oncology vol feb page f ta et al value serum bcl level advanced epithelial ovarian cancer pubmed oncol vol page fioretti p et al preoperative evaluation ca ca serum level patient ovarian mass pubmed eur j gynaecol oncol vol page first examination report issued indian patent application delnp dated nov freeman r et al resolution batch variation pyrolysis mass spectrometry bacteria use artificial neural network analysis antonie van leeuwenhoek pp vol furlong jw et al neural network analysis serial cardiac enzyme data clinical application artificial machine intelligence american journal clinical pathology jul pp vol g scambia et al measurement monoclonalantibodydefined antigen k serum patient ovarian cancer pubmed anicancer resarch vol julaug page gaskell sj electrospray principle practice journal mass spectrometry pp vol gb massi et al significance measurement several ocofetal antigen diagnosis management epithelial ovarian tumor pubmed european journal gynecology oncology vol page george se visualization design tool avid data mining selforganizing feature map international journal artificial intelligence tool pp vol gerhardt willie et al troponin sensitive specific diagnostic prognostic marker myocardial damage clinica chimica acta vol pp golub tr et al molecular classification cancer class discovery class prediction gene expression monitoring science oct pp vol goodacre et al correction mass spectral drift using artificial neural network analytical chemistry pp vol goodacre r et al discrimination methicillinresistant methicillinsusceptible staphylococcus aureus using pyrolysis mass spectrometry artificial neural network journal antimicrobal chemotherapy pp vol goodacre r et al identification discrimiation oral asaccharolytic eubacterium spp pyrolysis mass spectrometry artificial neural network current microbiology pp vol goodacre r et al quantitative analysis multivariate data using artificial neural network tutorial review application deconvolution pyrolysis mass spectrum zbl bakt pp vol goodacre r et al rapid identification urinary tract infection bacteria using hyperspectral wholeorganism fingerprinting artificial neural network microbiology pp vol goodacre r et al subspecies discrimination using pyrolysis mass spectrometry selforganising neural network propionibacterium acne isolated normal human skin zbl bakt pp vol gorelik elieser et al multiplexed immunobeadbased cytokine profiling early detection ovarian cancer short communication cancer epidemiology biomarkers prevention vol apr pp gray nab constraint learning machine classidication method analytical chemistry dec pp vol h kobayashi et al clinical evaluation circulating serum sialyl tn antigen level patient epithelial ovarian cancer pubmed j clin oncol vol jun page h koebl et al comparative study immunosuppressive acidic protein iap ca acutephase protein parameter ovarian cancer monitoring neoplasma vydavatelstvo slovenskej akademie vied veda sk vol xp jan pp h meden et al elevated serum level cerb oncogene product ovarian cancer patient pregnancy pubmed j cancer re clin oncol vol page h yabushita et al combination assay ca tpa iap cea ferritin serum ovarian cancer jubmed gynecol oncol vol jan page h zhang et al biomarker discovery ovarian cancer using selditofms pubmed gynecol oncol vol jul page hackett p et al rapid seldi biomarker protein profiling serum normal prostate cancer patient american association cancer research abstract mar pp vol halket jm et al deconvolution gas chromatographymass spectrometry urinary organic acidspotential pattern recognition automated identification metabolic disorder rapid communication mass spectrometry pp vol hashemi rr et al identifying testing signature nonvolatile biomolecules using tandem mass spectrum sigbio newsletter dec pp vol hausen et al determination neopterine human urine reversedphase highperformance liquid shromatography journal chromatography pp vol helfer la et al serum creactive protein independent prognostic variable patient ovarian cancer clinical cancer research american association cancer research u lnkddoi vol feb pp hellstrom et al wfdc protein biomarker ovarian carcinoma cancer research vol pp hellstrom ingegerd et al mesothelin variant released tumor cell diagnostic marker | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 2 | cancer epidemiology biomarkers prevention vol may pp hess kr et al classification regression tree analysis consecutive patient unknown primary carcinoma clinical cancer research nov pp vol holland jh adaption natural artificial system introductory analysis application biology control artificial intelligence pp mit press holmquist et al quantification human serum apolipoprotein ai zone immunoelectrophoresis assay procedure preparation ai standard clinica chimica acta vol pp hr rd bergen et al discovery ovarian cancer biomarkers serum using nanolc electrospray ionization tof fticr mass spectrometry pubmed dis marker vol page simon et al evaluation novel serum marker bh spondin dcr diagnosis early detection ovarian cancer pubmed gynecology oncology vol jul page inoue et al clinical value sialyl ssea antigen patient gynecologic tumor nihon sanka fujinka gakkai zasshi dec international search report written opinion international application pctus dated nov page j tosner et al serum prealbumin transferrin alpha acid glycoprotein patient gynecological carcinoma pubmed neoplasma vol page jain ak et al statistical pattern recognition review ieee transaction pattern analysis machine intelligence jan pp vol jellum e et al mass spectrometry diagnosis metabolic disorder biomedical environmental mass spectrometry pp vol jiekai yu et al integrated approach utilizing proteomics bioinformatics detect ovarian cancer journal zhejiang university science vol b pp jurs pc et al computerized learning machine appled chemical problem molecular formula determination low resolution mass spectrometry analytical chemistry jan pp vol kenyon rgw et al application neural network analysis pyrolysis mass spectrum zbl bakt pp vol kiem h et al using rough genetic kohonens neural network conceptual cluster discovery data mining new direction rough set data mining granularsoft computing international workshop rsfdgrc nov pp kizawa et al diagnostics value biochemical tumor marker serum patient cancer ovary pubmed nihon sanka fujinka gakkai zasshi vol pp knauf et al study nbk ca monoclonal antibody radioimmunoassay measuring serum antigen level ovarian cancer patient pubmed j obstet gynecol vol pt aug page koebl h tatra g bieglmayer c comparative study immunosuppressive acidic protein iap ca acutephase protein parameter ovarian cancer monitoring neoplasma vydavatelstvo slovenskej akademie vied veda sk vol january sk page xp issn koelbl h et al comparative study mucinlike carcinomaassociated antigen mca ca ca sea patient ovarian cancer pubmed neoplasma vol page koelbl h et al vergleichende untersuchungen ueber die wertigkeit von akutephaseproteinen und ca fuer da monitoring von patientinnen mit ovarialkarzinomcomparative study value acutephaseproteins ca monitoring patient maligna strahlentherapie und onkologie urban und vogel muenchen de vol january de page xp issn koelbl h et al vergleichende untersuchungen ueber die wertigkeit von akutephase proteinen und ca fuer da monitoring von patientinnen mit ovarialkazinomiicomparative study value acutephaseproteins ca monitoring patient maligna strahientherapie und onkologie urban und vogel muenchen de vol xp issn abstract p col paragraph figure table p col paragraph jan pp kohavi r et al wrapper feature subset selection artificial intelligence pp vol kohno h et al quantitative analysis scintiscan matrix computer japanese journal medical electronics biological engineering aug pp english abstract kohonen selforganization associative memory springer pp kohonen selforganizing map springer pp koivunen erkki et al identification biomarkers ovarian cancer using strong anionexchange protein chip potential use diagnosis prognosis pnas vol oct pp kr kozak et al characterization serum biomarkers detection early stage ovarian cancer pubmed proteomics vol nov page krishnamurthy et al detection pathogenic nonpathogenic bacteria matrixassisted laster desorption ionization timeofflight mass spectrometry rapid comms mass spectrometry pp vol kwata h et al survival ingested lacroferrin gastrointestinal tract adult mouse biochem j pp vol lambeck annechien j et al serum cytokine profiling diagnostic prognostic tool ovarian cancer potential role interleukin clinical cancer research vol apr pp langdon wb natural language text classification filtering trigram evolutionary nearest neighbour classifier cwi report jul pp lepage cecile et al gene profiling diagnostic marker il fgf complement ca serumbased marker epithelial ovarian cancer pubmed int j cancer vol apr pp lewis rj introduction classification regression tree cart analysis presented annual meeting society academic emergency medicine san franscisco ca pp li j et al proteomics bioinformatics approach identification serum biomarkers detect breast cancer clinical chemistry pp vol lim r et al neutrophil gelatinaseassociated lipocalin ngal earlyscreening biomarker ovarian cancer l ngal | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 3 | associated epidermal growth factorinduced epitheliomesenchymal transition pubmed int j cancer vol jun page lin yw et al plasma proteomic pattern biomarkers ovarian cancer international journal gynecol cancer vol supplemental janfeb pp liotta l et al molecular profiling human cancer nature genetics oct pp vol lockhardt et al genomics gene expression dna array nature jun pp vol loging tw et al identifying potential tumor marker antigen database mining rapid expression screening genome research sep pp vol lokshin anna e et al multipiexed biomarkers early detection ovarian cancer proceeding annual meeting american association cancer research th annual meeting american association cancer research vol apr p lopez f et al novel highthroughput workflow discovery identification serum carrier proteinbound peptide biomarker candidate ovarian cancer sample clin chem p lowry sr et al comparison various knearest neighbor voting scheme selftraining interpretive retrieval system identifying molecular substructure mass spectral data analytical chemistry oct pp vol lundqvist e nordstrom l sjovall k eneroth p evaluation seven different tumor marker establishment tumor marker panel gynecologic malignancy european journal gynaecological oncology european journal gynaecological oncology vol january page xp issn lundqvist ea et al evaluation seven different tumor marker establishment tumor marker panel gynecologic maligancies european journal gyynacological oncology sermes padova vol xp p col paragraph p col paragraph col paragraph p olumn paragraph col paragraph jan pp luo et al quantification confirmation flunixin equine plasma liquid chromatographquadrupole timeofflight tandem mass spetrometry journal chromatography b pp vol inoque et al sialyl lewisxi antigen patient gynecologic tumor pubmed obstet gynecol vol jan page macfie hjh et al use canonical variate analysis differentiation bacteria pyrolysis gasliquid chromatography journal general microbiology pp vol malins dc et al model dna structure achieve almost perfect discrimination normal prostrate beign prostatic hyperplasia bph adenocarcinoma high potential predicting bph prostrate cancer proceeding national academy science jan pp vol malki et al expression biological role prostaglandid synthasesox pathway human ovarian cancer cell pubmed cancer letter vol oct page marvin lf et al characterization novel speial officinalis neuropeptide using malditol m postsource secay analysis peptide pp vol mcsorley et al creactive protein concentration subsequent ovarian cancer risk obstetrics gynecology lippincott williams wilkins vol apr pp meinholdheerlein et al integrated clinicalgenomics approach identifies candidate multianalyte blood test serious ovarian carcinoma clinical cancer research vol jan pp meuzelaar hlc et al technique fast reproducible fingerprinting bacteria pyrolysis mass spectrometry analytical chemistry mar pp vol meyer b et al identification hnmr spectrum complex oligosaccharide artificial neural network science feb pp vol microsoft press computer dictionary second edition comprehensive standard business school library home microsoft press redmond wa pp moler ej et al analysis molecular profile data using generative discriminative method physiol genomics dec pp vol monnet et al clinical value creactive protein alpha glycoprotein acid transferrin assay homozygous sickle cell disease bulletin de la societe de pathologie exotique vol pp english abstract moore l e et al evaluation apoliprotein posttranclationally modified form transthyretin biomarkers ovarian cancer detection independent study population cancer epidemiol biomarkers prey p mor g et al serum protein marker early detection ovarian cancer pnas vol may pp moscova et al protein chip discovery secreted protein regulated phosphatidylinositol kinase pathway ovarian cancer cell line cancer research vol feb pp nakae et al preoperative asa psteppmtom eve noparler cpeemtary carbohydrate antigen predicting ovarian cancer pubmed j obstet gynaecol research vol jun page nikulin ae et al nearoptimal region selection feature space reduction novel preprocessing method classifying mr spectrum nmr biomedicine pp vol nilsson et al classification specied genus penicillium curie point pyrolysismass spectrometry followed multivariate analysis artificial neural network journal mass spectrometry pp vol nozawa et al galactosyltransferase isozyme ii gtii new tumor marker ovarian cancersespecially clear cell carcinoma nihon sanka fujinka gakkai zasshi sep vol nozawa et al clinical significance galactosyltransferase associate tumor gat new tumor marker ovarian cancerwith special reference discrimincation ovarian cancer endometriosis pubmed gan kagaku ryoho vol mar pp office action european patent application dated may page office action corresponding canadian patent application dated dec page office action corresponding canadian patent application dated nov page oh jmc et al database protein expression lung cancer proteomics pp | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 4 | vol olah tv et al simultaneous determination mixture drug candidate liquid chromatographyatmospheric pressure chemical ionization mass spectrometry vivo drug screening procedure rapid communication mass spectrometry pp vol paliouras et al human tisue kallikreins cancer biomarker family pubmed cancer letter vol apr page paulick r et al clinical significance different serum tumor marker gynecological malignancy pubmed sancer detect prevention vol page paweletz cp rapid protein display profiling cancer progression directly human tissue using protein biochip drug development research pp vol pct international search report written opinion issued international application pctus dated nov pei et al feature extraction using genetic algorithm proceeding st international symposium intelligent data engineering learning ideal oct pp springer hong kong petricoin iii ef et al clinical application proteomics journal nutrition jul pp vol petricoin iii ef et al serum proteomic pattern detection prostate cancer journal national cancer institute oct pp vol petricoin iii ef et al use proteomic pattern serum identify ovarian cancer lancet feb pp vol pictet v et al genetic algorithm collective sharing robust optimization financial application olsen associate research institute applied econonomics jan pp plebani et al combined use urinary ugp serum ca diagnosis gynecological cancer pubmed anticancer research vol b novdec page polanski et al list candidate cancer biomarkers targeted proteomics original research biomarker insight vol pp prior c et al potential urinary neopterin excretion differentiating chronic nona nonb hepatitus fatty liver lancet nov pp purohit pv et al discriminant model highthroughput proteomics mass spectrometer data abstract proteomicsclinical adaptation sep pp reed j trend commerical bioinformatics oscar grus biotechnology review mar pp reibnegger g et al neural network tool utilizing laboratiry information comparison linear discriminant analysis classification regression tree proceeding national academy science dec pp vol reichert et al application tissue receptor assay measurement serum follitropin fsh journal clinical endocrinology metabolism vol pp ricketts iw et al towards automated prescreening cervical smear mar application image processing mass health screening iee colloquium pp rose ad pharmacogenetics practice medicine nature jun pp vol rosty c et al identification hepatocarcinomaintestingpancreaspancreaticassociated protein biomarker pancreatic ductal adenocarcinoma protein biochip technology cancer research mar pp vol roy hk et al biomarkers early detection cancer inflammatory concept archive internal medicine american medical association chicago il u vol pp col paragraph sep pp rzymski p et al evaluation serum sicam ca patient ovarian tumorspreliminary report ginekol pol vol nov page salford system salford system white paper series pp online retrieved oct url sawada et al immunosuppresive acidic protein patient gynecologic cancer pubmed cancer vol aug page scambia g et al ca tumor marker gynecological malignancy pubmed gynecological oncology vol jun schmidt h et al microfabricated differenital mobility spectrometry pyrolysis gas chromatography chemical characterization bacteria anal chem pp vol scholler et al ca ovarian cancer biomarkers medicine pp dec scholler n et al beadbased elisa validation ovarian cancer early detection marker clinical cancer research vol apr pp schroll g et al application artificial intelligence chemical inference iii aliphatic ether diagnosed lowresolution mass spectrum nuclear madnetic resonance data journal american chemical society dec pp schutyser e et al identification biologically active chemokine isoforms ascitic fluid elevated level cclpulmonary acticationregulated chemokine ovarian carcinoma journal biological chemistry vol jul pp shaw ra et al infrared spectroscopy exfoliated cervical cell specimen analytical quantitative cytology histology aug pp vol shevchenko et al maldi quadupole timeofflight mass spectrometry powerful tool proteomic research analytical chemistry may pp vol shnayderman et al speciedspecific bacteria identification using differential mobility spectrometry bioinformatics pattern recognition anal chem pp vol simon et al bh novel membranebound protein candidate serum tissue biomarker ovarian cancer cancer research vol feb pp simon r development evaluation therapeutically relevant predictive classifier using gene expression profiling editorial journal national cancer institute vol sep pp skate et al pooling case specimen create standard serum set screening cancer biomarkers cancer epidemiol biomarkers prevention vol feb pp skate et al preoperative sensitiveity specificity earlystage ovarian cacner combining cancer antigen ca ca ca macrophage colonystimulating factor using mixture multivariate normal distribution journal clinical oncology original report vol bi oct pp strouthopoulos c et al pla using rlsa neural network engineering application artificial intelligence pp | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 5 | vol sun z et al protein chip system parallel analysis multitumor marker application cancer detection anticancer research vol pp taylor j et al deconvolution pyrolysis mass spectrum using genetic programming application identification eubacterium specie fems microbiology letter pp vol tong c et al mass spectral search method using neural network approach chemometrics intelligent laboratory system pp vol tong c et al mass spectral search method using neural network approach international joint conference neural network washington dc jul proceeding vol pp tsigkou et al total inhinin potential serum marker epithelial ovarian cancer journal clinical endocrinology metabolism vol jul pp tsukishiro et al preoperative serum thrombopoietin level highter patient ovarian cancer benign cyst pubmed eur j obstet gynecol reprod biol vol sep van de burg et al ca ovarian cancer netherlands journal medicine pp veenstra td et al multiple highresolution serum proteomic pattern ovarian cancer detection proceeding american association cancer research jul pp vol nd edition vlahou et al diagnosis ovarian cancer using decision tree classification mass spectral data journal biomedicine biotechnology vol pp von eggeling f et al mass spectrometry meet chip technology new proteomic tool cancer research electrophoresis pp vol voorhees kj et al approach pyrolysismass spectrometry data analysis biological material meuzelaar hlc computerenhanced analytical spectroscopy vol new york plenum press pp werther w et al classification mass spectrum comparison yesno classification method recognition simple structural property chemometrics intelligent laboratory system pp vol wilding et al application backpropogation neutral network diagnosis breast ovarian cancer cancer letter wilson k et al expression extracellular matrix protein tenascin malidnant benign ovarian tumour british journal cancer vol pp woongshick et al identification hemoglobin subunit potential serum biomarkers diagnosis prognosis ovarian cancer cancer science vol mar pp wu b et al comparison statistical method classification ovarian cancer using mass spectrometry data bioinformatics pp vol wu sp et al selditof m profiling plasma protein ovarian cancer taiwan journal obstet gynecol vol mar wythoff bj et al spectral peak verification recognition using multilayered neural network analytical chemistry dec pp vol xiao z et al quantitation serum prostatespecific membrane antigen novel protein biochip immunoassay discriminates beign malignant prostate disease cancer research aug pp vol xu et al lysophosphatidic acid potential biomarker ovarian gynecologic cancer dreliminary communication jama vol aug pp yao x et al evolving artificial neural network medical application proceeding first koreaaustralia joint workshop evolutionary computation sep pp yates iii jr mass spectrometry age proteome journal mass spectrometry pp vol ye b et al proteomicbased discovery characterization glycosylated eosinophilderived neurotoxin coohterminal osteopontin fragment ovarian cancer urine clin cancer re p yu j et al ovarian cancer identification based dimensionality reduction highthroughput mass spectrometry data bioinformatics pp vol yurkovetsky z et al development multimarker panel early detection endometrial cancer high diagnostic power prolactin gynecol oncol vol oct pp yurkovetsky z et al multiple biomarker panel early detection ovarian cancer future oncology future medicine ltd london gb vol dec pp zhang j dynamic formation selforganizing map obermayer h et al selforganizing map formation foundation neural computation oct pp zhang z et al three biomarkers identified serum proteomic analysis detection early stage ovarian cancer cancer research vol aug pp zhang z combining multiple biomarkers clinical diagnosisa review method issue center biomarker discovery department patholgy john hopkins medical institution page zhao c et al circulating haptoglobin independent prognosis factor serum patient epithelial ovarian cancer neoplasia brief article vol jan pp also published publication number publication date mya en usa en brpia en usb en cna en kra en epa en usa en usb en usa en jpa en usb en kra en epa en usa en epa en cnb en cac en sga en usa en woa en epa en krb en caa en similar document publication publication date title usb en predictive biomarkers ovarian cancer usa en predictive marker biomarker panel ovarian cancer aub en biomarker panel diagnostic method test kit ovarian cancer gorelik et al multiplexed immunobeadbased cytokine profiling early detection ovarian cancer cac en lung cancer biomarkers us thereof da et al early detection ovarian cancer usa en multifactorial assay cancer detection usa en method composition diagnosis ovarian cancer woa en enhanced diagnostic multimarker serological profiling wan et al correlation molecular tumor marker ca cea development | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 6 | progression epithelial ovarian cancer lokshin et al integrated development serum molecular marker early diagnosis breast cancer nolen circulating biomarkers study early detection ovarian cancer gentrymaharaj et al development identification tumor marker draghici et al epitomics serum screening early detection cancer microarrays using panel tumor antigen changqing proteomicsbased identification potential protein biomarkers epithelial ovarian cancer legal event date code title description fepp fee payment procedure free format text entity status set undiscounted original event code big entity status patent owner small entity assignment owner name correlogic system inc maryland free format text assignment assignor interestassignorsmansfield brian cyip ping famonkar surajand othersreelframe effective date owner name vermillion inc texas free format text assignment assignor interestassignorcorrelogic system increelframe effective date fepp fee payment procedure free format text entity status set small original event code smal entity status patent owner small entity stpp information status patent application granting procedure general free format text response nonfinal office action entered forwarded examiner stpp information status patent application granting procedure general free format text non final action mailed stpp information status patent application granting procedure general free format text response nonfinal office action entered forwarded examiner stcb information status application discontinuation free format text final rejection mailed stpp information status patent application granting procedure general free format text response final action forwarded examiner stpp information status patent application granting procedure general free format text notice allowance mailed application received office publication stpp information status patent application granting procedure general free format text awaiting tc resp issue fee paid stpp information status patent application granting procedure general free format text publication issue fee payment received stpp information status patent application granting procedure general free format text publication issue fee payment verified stcf information status patent grant free format text patented case assignment owner name aspira woman health inc texas free format text change nameassignorvermillion increelframe effective date mafp maintenance fee payment free format text payment maintenance fee th yr small entity original event code entity status patent owner small entity year fee payment | 1710.06481 | predictive biomarkers ovarian cancer | predictive biomarkers ovarian cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 7 | epa biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof google patent epa biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof google patent biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof download pdf info publication number epa epa epa epa epa ep ep ep ep ep ep ep ep ep authority ep european patent office prior art keywords serpina afp biomarker liver cancer serpina prior art date legal status legal status assumption legal conclusion google performed legal analysis make representation accuracy status listed withdrawn application number epa language german de french fr version epa en inventor youngsoo kim youngsuk lim hyunsoo kim injoon yeo current assignee listed assignee may inaccurate google performed legal analysis make representation warranty accuracy list snu rdb foundation original assignee seoul national university rdb foundation priority date priority date assumption legal conclusion google performed legal analysis make representation accuracy date listed filing date publication date priority claimed kr externalpriority application filed seoul national university rdb foundation filed critical seoul national university rdb foundation publication epa publication critical patentepaen publication epa publication critical patentepaen status withdrawn legalstatus critical current link espacenet epo gpi ep register global dossier discus liver cancer disease title claim abstract description biomarker substance title claim abstract description liver cirrhosis disease claim abstract description hepatic cirrhosis disease claim abstract description marker substance claim abstract description hepatitis disease claim abstract description hepatitis toxicity claim abstract description alphafetoproteins protein claim description alphafetoproteins human gene claim description serpina protein claim description serpina human gene claim description serpina human gene claim description apob human gene claim description cholesterol ester transfer protein protein claim description cholesterol ester transfer protein human gene claim description serpina protein claim description apob protein claim description serpina human gene claim description serpina protein claim description fga human gene claim description fga protein claim description itih human gene claim description itih protein claim description diagnosis method claim description catalase drug claim description ec protein claim description ec human gene claim description ppbp human gene claim description ppbp protein claim description mixture substance claim description fabp human gene claim description fabp protein claim description fetub human gene claim description fabpa protein claim description fcgbp human gene claim description fcgbp protein claim description fetub protein claim description sex hormonebinding globulin protein claim description sex hormonebinding globulin human gene claim description alb human gene claim description multiple reaction monitoring method claim description processed protein peptide human gene claim description processed protein peptide protein claim description itih protein claim description itih human gene claim description qsox protein claim description qsox human gene claim description azgp human gene claim description azgp protein claim description alb protein claim description myeloperoxidases protein claim description myeloperoxidases human gene claim description analytical method method claim description alb protein claim description apoa human gene claim description apolipoprotein l protein claim description apolipoprotein l human gene claim description ca human gene claim description ca protein claim description fbf protein claim description lgalsbp human gene claim description lgalsbp protein claim description cynt protein claim description igfals human gene claim description igfals protein claim description thb human gene claim description bco human gene claim description bco protein claim description ccd protein claim description cdh protein claim description cdh human gene claim description pon protein claim description pon human gene claim description serpind human gene claim description serpind protein claim description uchl protein claim description uchl human gene claim description apoa protein claim description selenop human gene claim description selenop protein claim description selenops specie claim description thb protein claim description apoc human gene claim description apoc protein claim description g human gene claim description glutathione synthase protein claim description hdlbp human gene claim description lum human gene claim description lumican protein claim description gp human gene claim description | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 8 | gp protein claim description bche human gene claim description bche protein claim description dib protein claim description apom human gene claim description ca human gene claim description ca protein claim description interleukin receptor accessory protein protein claim description interleukin receptor accessory protein human gene claim description scara protein claim description mtca protein claim description crl human gene claim description crl protein claim description clusterin human gene claim description clusterin protein claim description rbp human gene claim description rbp protein claim description vtn human gene claim description vitronectin protein claim description apoc human gene claim description apoc protein claim description hdlbp protein claim description blood anatomy claim description hepatitis b disease claim description apoh human gene claim description apoh protein claim description complement factor h protein claim description complement factor h human gene claim description fbln human gene claim description fbln protein claim description fgb human gene claim description fgb protein claim description jchain human gene claim description jchain protein claim description kng human gene claim description prdx human gene claim description prdx protein claim description pro human gene claim description pvr human gene claim description saa human gene claim description saa protein claim description vcam human gene claim description vcam protein claim description blood substance claim description apom protein claim description poliovirus receptor protein claim description serpina human gene claim description apoa human gene claim description btd human gene claim description biotinidase protein claim description esyt protein claim description esyt human gene claim description fcn human gene claim description fcn protein claim description fn human gene claim description ighm human gene claim description ighm protein claim description lrg human gene claim description lrg protein claim description proz human gene claim description proz protein claim description sa human gene claim description sa protein claim description uba human gene claim description uba protein claim description detection method method claim description hspb human gene claim description lmnb human gene claim description lamin b protein claim description kng protein claim description pro protein claim description psmd human gene claim description psmd protein claim description proc protein claim description human gene claim description protein claim description cndp human gene claim description carboxypeptidase b protein claim description carboxypeptidase b human gene claim description complement component c beta chain human gene claim description complement component c beta chain protein claim description entpd human gene claim description entpd protein claim description fcgra human gene claim description fcgra protein claim description icam human gene claim description itih protein claim description itih human gene claim description insulinlike growth factor binding protein human gene claim description insulinlike growth factor binding protein protein claim description insulinlike growth factor ii human gene claim description insulinlike growth factor ii protein claim description intercellular adhesion molecule protein claim description lcat human gene claim description lcat protein claim description orm human gene claim description orm protein claim description proc human gene claim description pzp protein claim description plasminogen protein claim description plasminogen human gene claim description rack protein claim description rack human gene claim description serpina protein claim description serum anatomy claim description vimentin protein claim description vimentin human gene claim description ambp protein claim description ambp human gene claim description apoa protein claim description fn protein claim description serpinc protein claim description serpinc human gene claim description serpinf protein claim description serpinf human gene claim description chemical substance application substance claim description hspb protein claim description mass spectrometry method claim description apof human gene claim description apof protein claim description cndp protein claim description klkb human gene claim description klkb protein claim description bioassay method claim description elisa method claim description nucleic acid protein claim description nucleic acid chemical class claim description sparc protein claim description | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 9 | complement c human gene claim description complement c protein claim description immunoassay method claim description microarray method claim description transferrin human gene claim description transferrin protein claim description alpha antitrypsin protein claim description alpha antitrypsin drug claim description amplification effect claim description development method claim description developmental process effect claim description nucleic acid amplification method method claim description proteasome nonatpase regulatory subunit human gene claim description proteasome nonatpase regulatory subunit protein claim description antithrombin iii drug claim description antithrombiniii human gene claim description antithrombiniii protein claim description apolipoprotein ai protein claim description apolipoprotein b protein claim description apolipoprotein ciii human gene claim description apolipoprotein ciii protein claim description apolipoproteins protein claim description brk protein claim description cholinesterase human gene claim description cholinesterase protein claim description coagulation factor ix human gene claim description coagulation factor vii human gene claim description complement component c human gene claim description complement component c protein claim description complement component c human gene claim description complement component c protein claim description complement component c human gene claim description complement component c protein claim description ec protein claim description f human gene claim description factor ix protein claim description factor vii protein claim description fetuinb protein claim description fibronectins protein claim description gcat protein claim description heparin cofactor ii human gene claim description heparin cofactor ii protein claim description pto protein claim description plasma kallikrein human gene claim description plasma kallikrein protein claim description protein ambp human gene claim description protein ambp protein claim description protein protein claim description prothrombin protein claim description prothrombin drug claim description selenoprotein p human gene claim description selenoprotein p protein claim description serum albumin protein claim description tsa protein claim description thrombospondin protein claim description alphamicroglobulin human gene claim description alphamicroglobulin protein claim description alphaantiplasmin human gene claim description alphaantiplasmin protein claim description apolipoprotein aiv protein claim description apolipoprotein f human gene claim description apolipoprotein f protein claim description cholinesterase drug claim description coagulation factor ix drug claim description coagulation factor vii drug claim description endoplasmin protein claim description factor ix drug claim description fibronectin effect claim description high density lipoprotein binding protein protein claim description kallistatin protein claim description pxr protein claim description vitamin binding protein human gene claim description vitamin binding protein protein claim description plasma anatomy claim description quantification method claim description vitro method claim description interalphainhibitor protein claim blood test method abstract description protein gene human gene description protein gene protein description protein nutrition description sample substance description hepatocellular carcinoma disease description hepatocellular carcinoma toxicity description auc effect description cancer disease description corresponding effect description antibody protein description antibody human gene description cell anatomy description sodiuminfluxstimulating peptide protein description bdagihxwwsansruhfffaoysan formic acid chemical compound oco bdagihxwwsansruhfffaoysan description material substance description sensitivity effect description substrate substance description ultrasonography method description liver anatomy description amino acid chemical class description biological sample substance description ion chemical class description neoplasm disease description liver disease disease description quantitative analysis method description tissue anatomy description validation analysis method description prognosis method description type analysis method description nitrocellulose substance description proteome protein description wevyahxrmpxwckuhfffaoysan acetonitrile chemical compound ccn wevyahxrmpxwckuhfffaoysan description amino acid nutrition description disease disease description imaging method method description labelling method description logistic regression method description magnetic resonance imaging method description maintenance location effect description nitrocellulos polymer description qualitative analysis method description capillary anatomy description chronic hepatitis disease description hepatitis viral disease description messenger rna protein description nucleic protein protein description trypsin human gene description trypsin protein description decreasing effect description diagnostic procedure method description drug substance description effect effect description engineering process method description experimental | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 10 | method method description formic acid nutrition description glass substance description messenger rna polymer description multivariate analysis method description proteomic method description radioimmunoassay method description surgical procedure method description trypsin drug description trypsin substance description viral hepatitis disease description aptamer polymer description ascites disease description afynaddzulbejauhfffaoysan bicinchoninic acid chemical compound cccccnccccccccccncoocccooc afynaddzulbejauhfffaoysan description enzyme drug description enzyme human gene description enzyme protein description kdxkernsbixsrkyfkpbyrvsan llysine chemical compound nccccchncoo kdxkernsbixsrkyfkpbyrvsan description ffearjckvfrzrrbypyzucnsan lmethionine chemical compound csccchncoo ffearjckvfrzrrbypyzucnsan description metastasis disease description abnormal effect effect description bead substance description binding effect description biopsy method description chemical reaction method description chemical reaction reagent substance description colorant substance description computed tomography method description crossvalidation method description data analysis method description detectable effect description differentiation effect description disease infectious agent disease description immunoelectrophoresis method description liver function effect description manufacturing process method description method method description normalization method description peptidomimetic substance description ozaifhulbgxakxuhfffaoysan precursor substance nccccnnccccn ozaifhulbgxakxuhfffaoysan description product substance description radioactive effect description research method description statistical method method description survival effect description vascular effect description western blot method description abdominal pain disease description alcohol abuse disease description alcoholic hepatitis disease description alkaline phosphatase human gene description alkaline phosphatase protein description arginine substance description bile duct anatomy description cholangiocarcinoma disease description chronic hepatitis b disease description coma hepatic disease description complementary dna polymer description qivbcdijiajpqssecbinfhsan dtryptophane chemical compound ccccccchncoocncc qivbcdijiajpqssecbinfhsan description dna amplification effect description fibrosis disease description gastrointestinal hemorrhage disease description hp human gene description hspab protein description hspab human gene description haemorrhage disease description haptoglobin protein description hepatic cancer disease description hepatic neoplasm disease description hepatic rupture disease description hepatitis b virus specie description hepatitis alcoholic disease description hepatocellular injury disease description hepatocytes anatomy description homo specie description horseradish peroxidase protein description hypertrophy disease description immunoglobulin protein description immunoglobulin g protein description inflammation disease description jaundice disease description xujnekjlayxeshreohclbhsan lcysteine chemical compound scchncoo xujnekjlayxeshreohclbhsan description mtcfgrxmjlqnbgreohclbhsan lserine chemical compound occhncoo mtcfgrxmjlqnbgreohclbhsan description mammalia specie description martes zibellina specie description muscle weakness disease description muscular weakness disease description nylon substance description oxidoreductase human gene description oxidoreductase protein description pain disease description peptidase human gene description peptidase protein description polystyrene substance description portal system anatomy description sarcoma disease description scar disease description gsejcltvzplzkyuhfffaoysan tris chemical compound occnccocco gsejcltvzplzkyuhfffaoysan description tris buffer substance description varix oesophageal disease description virus specie description albumin drug description alcohol use disease disease description antigenic effect description binding buffer substance description ybjhbahktgyvgtzkwxmuahsan biotin chemical compound nconchchcccccooscch ybjhbahktgyvgtzkwxmuahsan description biotin drug description biotin nutrition description biotin substance description bleeding toxicity description bleeding effect description calculation method method description capillar electrophoresis method description carcinogenesis toxicity description carcinoma disease description cell killing effect description centrifugation method description chronic effect description complement effect description complementary dna substance description confocal microscopy method description cysteine nutrition description cytolysis effect description death effect description desalting method description diagram method description digestion effect description dipping method method description drug drug description enhancing effect description esophageal varix disease description evaluation method description exacerbation effect description fibrosis effect description glycans polymer description hepatic effect description hepatic coma disease description immunodiffusion effect description immunoprecipitation method description infiltration method description inflammatory process effect description internal standard material substance description intraperitoneal administration method description ligand substance description limiting effect description liquid chromatography method description liquid chromatographytandem mass spectrometry method description machine learning method description magnetic particle substance description malignant effect description | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 11 | measurement method description membrane substance description metabolic effect description metastatic cancer disease description microparticle substance description monoclonal antibody protein description monoclonal antibody human gene description nanoparticle substance description nebulizer substance description necrotic cell death effect description nucleic acid array method description nylon polymer description optical effect description organ anatomy description oxidation effect description oxidation reaction method description particle substance description pathological effect description pathway effect description physiological process function effect description plastic substance description polyclonal antibody protein description polypeptide polymer description polysaccharide polymer description polysaccharide substance description polysaccharide polymer description polystyrene polymer description preparation method method description preventive effect description processing method method description progressing effect description protease nutrition description protein array method description protein immunostaining method description protein marker substance description radioactive substance substance description random forest analysis method description reaction effect description receptor human gene description receptor protein description reduced effect description regenerating effect description rendering method description scar toxicity description scar effect description secreting effect description separation method method description solid substance description solution substance description spectral effect description spectrum method description substance substance description supernatant substance description suspension substance description synthesizing effect description tandem mass spectrometry method description tomography method description transcription effect description transferrin substance description xlyofnoqvpjjnpuhfffaoysan water substance xlyofnoqvpjjnpuhfffaoysan description water type substance description image classification gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite involving compound identifable body fluid gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnspecifically defined cancer gnspecifically defined cancer liver pancreas kidney gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gndetermining risk developing disease gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gnpredicting monitoring response treatment eg selection therapy based assay result personalised medicine prognosis gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gnstaging disease complication associated disease abstract present application discloses biomarker capable monitoring diagnosing onset liver cancer early stage highrisk patient group liver cancer method monitoring detecting diagnosing onset liver cancer early stage highrisk group liver cancer using marker biomarker according present application allows liver cancer accurately diagnosed simple blood test early stage highrisk patient group liver cancer inclusive liver cancer hepatitis liver cirrhosis description background invention field invention preset disclosure related monitoring diagnosing onset liver cancer highrisk group liver cancer description related art hepatocellular carcinoma hcc type ablof cancer prevalent adult liver cancer rd leading cause cancer related death worldwide account primary liver cancersferrin g aguilarmelero p rodriguezperalvarez monteroalvarez j l de la mata hepatic medicine evidence research although study hepatocellular carcinoma continue symptom well known still difficult diagnose disease early stage survival rate diagnosis low xiao j f et al journal ofproteome research complete removal cancer surgery required however surgery possible case patient cirrhosis hepatitis b clearly classified highrisk group developing liver cancer hepatitis b patient develop liver cancer cirrhosis patient directly develop liver cancer risk developing liver cancer patient hepatitis b time higher general population annual incidence liver cancer | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 12 | therefore patient hepatitis b severe cirrhosis early diagnosis liver cancer important preventing liver cancer prognosis patient great influence possibility developing liver cancer current diagnostic method liver cancer includes imaging method ultrasonography computed tomography magnetic resonance imaging however disadvantage detection small tumor difficult expensive afp main noninvasive method early detection liver cancer people high risk developing however specificity remained level afp increased patient benign liver disease alcoholic hepatitis viral hepatitis cirrhosis resulting low specificity insufficient use biomarker early diagnosis liver cancer especially disease progress cirrhosis liver cancer hepatitis liver cancer ie high risk liver cancer liver diagnosed early stage thus difficult detect diagnose early liver cancer developed hepatitis using marker generally used diagnose liver cancer advanced stage early liver cancer sensitivity ultrasonography recommended routine screening patient highrisk liver cancer therefore necessary overcome limitation individual test single marker improving accuracy diagnosis combining several marker continuous development biomarkers improved specificity sensitivity suitable detection liver cancer combining multiple biomarkers distinct pathological physiological pathway potential overcome shortcoming enhance risk stratification significantly improve risk prediction using multimarker approach kr patent application publication patent discloses marker combination marker diagnose prognosis monitoring liver cancer however marker disclosed therein difficult use monitoring detecting patient high risk liver cancer early stage liver cancer marker developed normal liver cirrhosis hepatitis b patient comparison patient advanced stage liver cancer kr patent application publication discloses method assessing risk subject chronic hepatitis liver cirrhosis develop liver cancer summary invention present disclosure provide biomarkers make possible surveillance onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer one aspect present disclosure provides biomarkers surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer use present biomarkers may employed compositiona kit comprising material detecting least one present biomarkers blood method surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer method detecting least one present biomarkers surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient present biomarkers tested sample particularly highrisk group patient developing liver cancer includes hepatitis liver cirrhosis patient present biomarkers surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer least one marker selected group consisting orm alphaacid glycoprotein serpina alphaantitrypsin serpinf alphaantiplasmin alphamacroglobulin alb serum albumin serpinc antithrombiniii apoa apolipoprotein ai apoa apolipoprotein aiv apob apolipoprotein b apoc apolipoprotein ciii apoc apolipoprotein civ apof apolipoprotein f apoh betaglycoprotein apol apolipoprotein l apom apolipoprotein bco betabetacarotene oxygenase btd biotinidase crl complement cr subcomponentlike protein cdh cadherin ca carbonic anhydrase ca carbonic anhydrase cat catalase cpb carboxypeptidase b cetp cholesteryl ester transfer protein cfh complement factor h c complement c cb complement component c beta chain c complement component c ppbp platelet basic protein hspb endoplasmin entpd ectonucleoside triphosphate diphosphohydrolase esyt extended synaptotagmin f coagulation factor vii f coagulation factor ix fabp fatty acidbinding protein liver fcgbp iggfcbinding protein fetub fetuinb fga fibrinogen alpha chain fgb fibrinogen beta chain rack receptor activated protein c kinase gp platelet glycoprotein v g glutathione synthetase serpind heparin cofactor icam intercellular adhesion molecule ighm immunoglobulin heavy constant mu ilrap interleukin receptor accessory protein itih interalphatrypsin inhibitor heavy chain h itih interalphatrypsin inhibitor heavy chain h kng kininogen lmnb laminb mpo myeloperoxidase pon serum paraoxonasearylesterase prdx peroxiredoxin proc vitamin kdependent protein c pro vitamin kdependent protein proz vitamin kdependent protein z psmd proteasome nonatpase regulatory subunit pvr poliovirus receptor rbp retinolbinding protein sa protein sa saa serum amyloid protein uba sumoactivating enzyme subunit selenop selenoprotein p sparc sparc tf serotransferrin thb thrombospondin uchl ubiquitin carboxylterminal hydrolase isozyme l vcam vascular cell adhesion protein hdlbp vigilin vim vimentin azgp zincalphaglycoprotein serpina protein zdependent protease inhibitor lrg leucinerich alphaglycoprotein igfals insulinlike growth factorbinding protein complex acid labile subunit ambp protein ambp cleaved alphamicroglobulin bche cholinesterase clu clusterin cndp betaalahis dipeptidase c complement component c c complement component c fbln fibulin fcgra low affinity immunoglobulin gamma fc region receptor iiia fcn ficolin afp alphafetoprotein fn fibronectin igfbp insulinlike growth factorbinding protein igf insulinlike growth factor ii jchain immunoglobulin j chain serpina plasma serine protease inhibitor itih interalphatrypsin inhibitor heavy chain h serpina kallistatin klkb plasma kallikrein lcat phosphatidylcholinesterol acyltransferase lgalsbp galectinbinding protein lum lumican plg plasminogen qsox sulfhydryl oxidase shbg sex hormonebinding globulin f prothrombin gc vitamin dbinding protein vtn vitronectin one embodiment least one marker particularly selected group consisting orm alphaacid glycoprotein serpina alphaantitrypsin serpinf alphaantiplasmin alphamacroglobulin | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 13 | alb serum albumin serpinc antithrombiniii apoa apolipoprotein ai apoa apolipoprotein aiv apob apolipoprotein b apoc apolipoprotein ciii apoc apolipoprotein civ apof apolipoprotein f apoh betaglycoprotein apol apolipoprotein l apom apolipoprotein bco betabetacarotene oxygenase btd biotinidase crl complement cr subcomponentlike protein cdh cadherin ca carbonic anhydrase ca carbonic anhydrase cat catalase cpb carboxypeptidase b cetp cholesteryl ester transfer protein cfh complement factor h c complement c cb complement component c beta chain c complement component c ppbp platelet basic protein hspb endoplasmin entpd ectonucleoside triphosphate diphosphohydrolase esyt extended synaptotagmin f coagulation factor vii f coagulation factor ix fabp fatty acidbinding protein liver fcgbp iggfcbinding protein fetub fetuinb fga fibrinogen alpha chain fgb fibrinogen beta chain rack receptor activated protein c kinase gp platelet glycoprotein v g glutathione synthetase serpind heparin cofactor icam intercellular adhesion molecule ighm immunoglobulin heavy constant mu ilrap interleukin receptor accessory protein itih interalphatrypsin inhibitor heavy chain h itih interalphatrypsin inhibitor heavy chain h kng kininogen lmnb laminb mpo myeloperoxidase pon serum paraoxonasearylesterase prdx peroxiredoxin proc vitamin kdependent protein c pro vitamin kdependent protein proz vitamin kdependent protein z psmd proteasome nonatpase regulatory subunit pvr pvs poliovirus receptor rbp retinolbinding protein sa protein sa saa serum amyloid protein uba sumoactivating enzyme subunit selenop selenoprotein p sparc sparc tf serotransferrin thb thrombospondin uchl ubiquitin carboxylterminal hydrolase isozyme l vcam vascular cell adhesion protein hdlbp vigilin vim vimentin azgp zincalphaglycoprotein serpina protein zdependent protease inhibitor one embodiment marker may comprise least one marker selected group consisting lrg leucinerich alphaglycoprotein igfals insulinlike growth factorbinding protein complex acid labile subunit ambp protein ambp cleaved alphamicroglobulin bche cholinesterase clu clusterin cndp betaalahis dipeptidase c complement component c c complement component c fbln fibulin fcgra low affinity immunoglobulin gamma fc region receptor iiia fcn ficolin afp alphafetoprotein fn fibronectin igfbp insulinlike growth factorbinding protein igf insulinlike growth factor ii jchain immunoglobulin j chain serpina plasma serine protease inhibitor itih interalphatrypsin inhibitor heavy chain h serpina kallistatin klkb plasma kallikrein lcat phosphatidylcholinesterol acyltransferase lgalsbp galectinbinding protein lum lumican plg plasminogen qsox sulfhydryl oxidase shbg sex hormonebinding globulin f prothrombin gc vitamin dbinding protein vtn vitronectin one embodiment marker surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer least one marker selected group consisting serpina alb apob apoc apoc apol btd cdh ca cat cetp c esyt fcgbp fetub fga gp g serpind ilrap itih lmnb mpo pon prdx pvr saa uba selenop tf thb uchl hdlbp azgp serpina one embodiment marker surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer may comprise least one marker selected group consisting lrg c afp jchain serpina serpina lgalsbp lum qsox shbg f vtn one embodiment highrisk group patient developing liver cancer hepatitis patient marker may used surveillancemonitoing onset liver cancer early diagnosis liver cancer hepatitis patient least one marker selected group consisting orm alb serpinc apoa apoa apob apoc apoc apof apol apoh apom bco cdh cpb ca ca cat cetp cb ppbp f fabp entpd f fcgbp fetub fga rack gp serpind icam igf ilrap itih itih kng pon proc pro proz psmd rbp sa saa selenop sparc thb vcam vim serpina one embodiment marker surveillancemonitoring onset liver cancer early diagnosis liver cancer hepatitis patient may comprise least one marker selected group consisting igfals bche clu cndp c fcgra fcn afp igfbp itih serpina klkb lcat lgalsbp plg qsox shbg f gc vtn one embodiment highrisk group patient developing liver cancer liver cirrhosis patient marker may used surveillancemonitoring onset liver cancer early diagnosis liver cancer liver cirrhosis patient least one marker selected group consisting serpinf apoa apob apol apom bcocrl ca cat cetp cfh c ppbp hspb f fabp fga fgb g serpind ighm itih mpo pon rbp selenop uchl hdlbp azgp serpina one embodiment marker surveillancemonitoring onset liver cancer early diagnosis liver cancer liver cirrhosis patient may comprise least one marker selected group consisting ambp bche clu c c fbln afp fn serpina serpina lum qsox shbg f one embodiment present marker used combination two marker surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group developing liver cancer combination alb apob apol btd cdh cat cetp esyt afp fga gp g serpina itih itih erpina lum mpo pon pvr saa serpina apob cat cetp c afp fetub fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina lrg apoc cetp afp serpina tf serpina apoc afp serpina lmnb mpo pvr serpina serpina apob cat cetp afp fetub fga g serpina itih serpina uba shbg f thb thb serpina cetp c afp ilrap serpina lgalsbp mpo hdlbp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpina itih serpina prdx selenop shbg thb uchl serpina alb apob ca cetp afp fetub serpina itih serpina mpo f thb serpina particular combination two marker apob cat cetp c afp fetub fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpina itih serpina prdx | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 14 | selenop shbg thb uchl serpina one embodiment present marker used combination two marker surveillancemonitoring onset liver cancer early diagnosis liver cancer particularly hepatitis patient belong highrisk group developing liver cancer combination igfals apoa c ppbp f fabp fcgbp afp itih serpina serpina igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb igfals cetp c ppbp fabp afp ilrap itih itih serpina sa serpina alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina igfals ca cetp c ppbp fabp fcgbp fcn afp fga itih serpina serpina igfals serpinc apoa cat c ppbp f fcgbp afp fga itih serpina proz qsox serpina apob apoc apoh cdh ppbp fabp afp fetub serpina serpina apob apoc apoh apom cat ppbp fabp afp fetub itih serpina serpina particular combination two marker igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina one embodiment present marker used combination two marker surveillancemonitoring onset liver cancer early diagnosis liver cancer particularly liver cirrhosis patient belong highrisk group developing liver cancer combination apob apol cat cetp c fabp afp fga fn ighm serpina itih serpina pon pon serpina bcocat cetp cfh bche afp fga serpina selenop uchl azgp serpina ambp apob apom crl cat cetp clu ppbp hspb f fga g serpina serpina rbp hdlbp azgp serpina apoa apob crl cetp afp fgb serpind serpina serpina lum qsox shbg serpina apoa apob apol cetp c fbln afp fga serpina itih serpina serpinf apob cetp fbln afp fga serpina rbp hdlbp serpina apob cetp afp fga serpina serpina f serpina apoa apob apol ca cetp clu c afp fga serpina itih serpina azgp serpina particular combination two marker bco cat cetp cfh bche afp fga serpina selenop uchl azgp serpina apoa apob crl cetp afp fgb serpind serpina serpina lum qsox shbg serpina present marker detected blood sample including plasma serum whole blood one embodiment present marker tested particularly plasma sample present biomarkers may provided composition kit elisa dip stick rapid kit mass spectrometry microarray nucleic amplification immunoassay one embodiment present biomarkers provided composition kit mass spectrometry particularly mrm analysis peptide present marker used mrm analysis one listed table aspect present disclosure provides method surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer comprising step detecting marker disclosed herein combination thereof method detecting present biomarkers combination marker disclosed herein surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient one embodiment method surveillancemonitoring onset liver cancer early diagnosis liver cancer highrisk group patient developing liver cancer method comprising step detecting quantifying present marker combination thereof sample subject need thereof comparing result previous step corresponding marker control sample determining sample subject afflicted early liver cancer change result subject comparison control wherein control sample sample hepatitis b patient cirrhosis patient without liver cancer developed liver cancer present biomarkers may detected elisa dip stick rapid kit mass spectrometry microarray nucleic amplification immunoassay like one embodiment present biomarkers analyzed sample using particularly mass spectrometry particularly mrm peptide marker may used mrm analysis listed table advantageous effect present biomarkers method using accurately diagnose risk developing liver cancer liver cancer early stage highrisk group patient hepatitis b cirrhosis particular current clinical guideline early diagnosis hepatocellular carcinoma highrisk group patient hepatitis b cirrhosis visit clinic every six month ultrasound afp test however ultrasound examination require specialist degree diagnosis may vary widely depending proficiency level therefore employing marker according present disclosure possible surveillancemonitoring early diagnosis onset liver cancer early stage including extremely early stage detecting expression level marker combination marker patient high risk developing liver cancer including hepatitis cirrhosis patient also mrm multiple reaction monitoring based mass spectrometry used peptide marker present disclosure easy applied mrm assay replace conventional immunoassay currently used clinical field thus accuracy diagnosis liver cancer especially liver cancer early stage significantly improved addition marker according present disclosure useful early detection liver cancer home general clinical use noninvasive way using blood patient pain economic burden reduced testing liver cancer | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 15 | simple blood test medical examination bring medical cost reduction national perspective brief description drawing fig figb figc figd fige fig figg figh roc receiver operating characteristic analysis result present biomarkers refer table showed expression level different control roc analysis refer zweig mh campbell g receiveroperating characteristic roc plot fundamental evaluation tool clinical medicine clinical chemistry roc analysis generally used make decision accuracy effectiveness particular marker diagnosis prognosis disease roc curve analysis model evaluated based sensitivity specificity area curve auc calculated roc curve representing degree measure sensitivity specificity used confirm diagnostic accuracy particular marker result show high degree diagnostic accuracy present biomarkers figure diagonal segment produced tie fig schematically show multivariate analysis strategy accordance one embodiment present disclosure present disclosure logistic regression support vector machine method used analysis order prevent overfitting resampling used secure statistical reliability analysis result resampling method fold cross validation kim h et al sci rep aug kim h et al mol cell proteomics jul used bootstrap method data used divided ratio fig schematic diagram mrm analysis detailed description embodiment present disclosure based part discovery marker show differential expression blood sample hepatitis b liver cirrhosis group classified highrisk group developing liver cancer liver cancer group early stage le cm diameter thus advantageously used early detection diagnosis liver cancer highrisk group therefore one aspect present disclosure provided least one marker composition comprising material detecting least one marker blood sample early diagnosis liver cancer subject high risk developing liver cancer least one marker present disclosure selected group consisting orm alphaacid glycoprotein serpina alphaantitrypsin serpinf alphaantiplasmin alphamacroglobulin alb serum albumin serpinc antithrombiniii apoa apolipoprotein ai apoa apolipoprotein aiv apob apolipoprotein b apoc apolipoprotein ciii apoc apolipoprotein civ apof apolipoprotein f apoh betaglycoprotein apol apolipoprotein l apom apolipoprotein bco betabetacarotene oxygenase btd biotinidase crl complement cr subcomponentlike protein cdh cadherin ca carbonic anhydrase ca carbonic anhydrase cat catalase cpb carboxypeptidase b cetp cholesteryl ester transfer protein cfh complement factor h c complement c cb complement component c beta chain c complement component c ppbp platelet basic protein hspb endoplasmin entpd ectonucleoside triphosphate diphosphohydrolase esyt extended synaptotagmin f coagulation factor vii f coagulation factor ix fabp fatty acidbinding protein liver fcgbp iggfcbinding protein fetub fetuinb fga fibrinogen alpha chain fgb fibrinogen beta chain rack receptor activated protein c kinase gp platelet glycoprotein v g glutathione synthetase serpind heparin cofactor icam intercellular adhesion molecule ighm immunoglobulin heavy constant mu ilrap interleukin receptor accessory protein itih interalphatrypsin inhibitor heavy chain h itih interalphatrypsin inhibitor heavy chain h kng kininogen lmnb laminbl mpo myeloperoxidase pon serum paraoxonasearylesterase prdx peroxiredoxin proc vitamin kdependent protein c pro vitamin kdependent protein proz vitamin kdependent protein z psmd proteasome nonatpase regulatory subunit pvr poliovirus receptor rbp retinolbinding protein sa protein sa saa serum amyloid protein uba sumoactivating enzyme subunit selenop selenoprotein p sparc sparc tf serotransferrin thb thrombospondin uchl ubiquitin carboxylterminal hydrolase isozyme l vcam vascular cell adhesion protein hdlbp vigilin vim vimentin azgp zincalphaglycoprotein serpina protein zdependent protease inhibitor lrg leucinerich alphaglycoprotein igfals insulinlike growth factorbinding protein complex acid labile subunit ambp protein ambp cleaved alphamicroglobulin bche cholinesterase clu clusterin cndp betaalahis dipeptidase c complement component c c complement component c fbln fibulin fcgra low affinity immunoglobulin gamma fc region receptor iiia fcn ficolin afp alphafetoprotein fn fibronectin igfbp insulinlike growth factorbinding protein igf insulinlike growth factor ii jchain immunoglobulin j chain serpina plasma serine protease inhibitor itih interalphatrypsin inhibitor heavy chain h serpina kallistatin klkb plasma kallikrein lcat phosphatidylcholinesterol acyltransferase lgalsbp galectinbinding protein lum lumican plg plasminogen qsox sulfhydryl oxidase shbg sex hormonebinding globulin f prothrombin gc vitamin dbinding protein vtn vitronectin one embodiment present disclosure least one marker selected group consisting orm serpina serpinf alb serpinc apoa apoa apob apoc apoc apof apoh apol apom bco btd crl cdh ca ca cat cpb cetp cfh c complement c cb c ppbp hspb entpd esyt f f fabp fcgbp fetub fga fgb rack gp g serpind icam ighm ilrap itih itih kng lmnb mpo pon prdx proc pro proz psmd pvr rbp sa saa uba selenop sparc tf thb uchl vcam hdlbp vim azgp serpina embodiment present disclosure least one marker selected group consisting lrg igfals ambp bche clu cndp c c fbln fcgra fcn afp fn igfbp igf jchain serpina itih serpina klkb lcat lgalsbp lum plg qsox shbg f gc vtn biomarkers marker present disclosure marker early detection liver cancer patient highrisk developing liver cancer include protein polypeptide derived protein gene encoding protein fragment thereof show change concentration sample especially blood derived patient liver cancer compared control sample biomarker according present disclosure | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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"id": "1710.06481"
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1710.06481 | 16 | increased decreased amount blood liver cancer patient compared control sample sequence marker foundsearched example uniprot wwwuniprotorg id disclosed table present marker useful early diagnosis liver cancer subject highrisk developing liver cancer liver cancer tumor hepatocytes lose function continuous various stimulus transform cancer cell endowed endless selfproliferation spread surrounding distant place includes primary cancer metastatic cancer occurs liver migrated organ primary liver cancer includes hepatocellular carcinoma caused abnormal liver cell cholangiocarcinoma caused abnormal bile duct cell vascular sarcoma hepatocellular carcinoma hcc one embodiment according present disclosure liver cancer primary malignant tumor occurring liver tissue hepatocellular carcinoma hepatocellular carcinoma common high risk patient risk factor alcohol abuse viral hepatitis metabolic liver disease including liver cirrhosis hepatocellular carcinoma fibrous stromal thus bleeding cell necrosis cause vascular infiltration portal system severe case hepatic rupture intraperitoneal blood effusion highrisk group developing liver cancer herein patient hepatitis including viral hepatitis hepatitis b liver disease including liver cirrhosis patient classified patient high risk developing liver cancer medical field due high incidence liver cancer screening test surveillance test diagnosing progression liver cancer high risk group key early diagnosis effective treatment present disclosure provides marker optimal effective effect use hepatitis infectious disease manifest infection caused virus particularly hepatitis b virus infection includes particular chronic hepatitis chronic hepatitis caused hepatitis b virus develop cirrhosis liver cancer hepatitis b also develop liver cancer liver cirrhosis chronic inflammation liver cause regenerative nodule fibrosis liver tissue resulting hepatocellular damage scar decreased liver function ascites gastrointestinal bleeding hepatic coma since liver cirrhosis patient diagnosed liver cancer early diagnosis liver cancer particularly important highrisk group marker according present disclosure diagnose liver cancer early highrisk group developing liver cancer classification according developmental stage liver cancer grade known art example edmondson steiner grading system based histological grade tumor differentiation pirisi et al arch pathol lab med dec also american joint committee cancer ajcc tnm staging liver tumor th ed latest edition liver cancer study group japan lcsgjt hcc tnm tumor node metastasis staging may referred according reference hepatocellular carcinoma divided stage according progression stage marker according present disclosure detect stage precancerous stage liver cancer another embodiment early diagnosis includes diagnosis extremely early stage liver cancer le cm liver cancer cell tissue precancerous condition premalignant condition malignant potential onset cancer extremely early stage detection cancer dramatically improve efficacy treatment survival rate diagnosis staging cancer described determined general according type cancer cell degree differentiation andor degree metastasis etc tissue obtained surgery biopsy treatment prognosis solid tumor general determined tnm stage contrast case liver cancer tnm staging alone may make difficult choose optimal treatment andor predict prognosis liver cancer patient also chronic liver disease limit selection optical treatment method liver cancer unlike carcinoma liver cancer also diagnosed imaging test currently clinical guideline early diagnosis hepatocellular carcinoma patient highrisk including hepatitis b cirrhosis patient visit every six month ultrasound afp test however ultrasound examination requires specialist degree diagnosis varies widely depending proficiency specialist therefore using marker according present disclosure possible surveillance andor early diagnosis onset liver cancer including liver cancer extremely early stage detecting marker combination marker expression status marker patient high risk liver cancer including hepatitis cirrhosis patient one embodiment according present disclosure marker combination marker exhibit differential expression high auc value primary secondary tertiary sample group described example herein limited thereto one embodiment marker early diagnosis liver cancer high risk liver cancer group include least one marker selected group consisting serpina alb apob apoc apoc apol btd cdh ca cat cetp c esyt fcgbp fetub fga gp g serpind ilrap itih lmnb mpo pon prdx pvr saa uba selenop tf thb uchl hdlbp azgp serpina marker may comprise least one marker selected group consisting lrg c afp jchain serpina serpina lgalsbp lum qsox shbg f vtn marker according present disclosure early diagnose liver cancer hepatitis patient among highrisk group liver cancer one embodiment marker | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 17 | least one marker selected group consisting orm alb serpinc apoa apoa apob apoc apoc apof apol apoh apom bco cdh cpb ca ca cat cetp cb ppbp f fabp entpd f fcgbp fetub fga rack gp serpind icam igf ilrap itih itih kng pon proc pro proz psmd rbp sa saa selenop sparc thb vcam vim serpina marker may comprise least one marker selected group consisting igfals bche clu cndp c fcgra fcn afp igfbp itih serpina klkb lcat lgalsbp plg qsox shbg f gc vtn marker according present disclosure early diagnose liver cancer liver cirrhosis patient among highrisk group liver cancer one embodiment marker least one marker selected group consisting serpinf apoa apob apol apom bcocrl ca cat cetp cfh c ppbp hspb f fabp fga fgb g serpind ighm itih mpo pon qsox rbp selenop uchl hdlbp azgp serpina marker may comprise least one marker selected group consisting ambp bche clu c c fbln afp fn serpina serpina lum shbg f marker according present disclosure may used alone combination least two marker example marker used combination conventional marker may also used conjunction existing marker andor conventional diagnostic method liver ultrasound like skilled art able select without difficulty combination marker meet desired sensitivity specificity method logistic regression analysis support vector machine reference method described example herein one embodiment comparison highrisk liver cancer group hbvlc liver cancer group least one marker selected serpina lrg alb apob apoc apoc apol btd cdh ca cat cetp c c esyt fcgbp afp fetub fga gp g serpind jchain ilrap serpina itih serpina lgalsbp lmnb lum mpo pon prdx pvr qsox saa uba selenop shbg f tf thb uchl hdlbp vtn azgp serpina may combined various combination example one embodiment combination marker found high diagnostic power auc showed auc separate independent data set validation set indicating good diagnostic power embodiment comparison highrisk liver cancer group hbvlc liver cancer group least one marker selected alb apob ca cat cetp c c fcgbp afp fetub fga gp serpind jchain serpina itih serpina lgalsbp mpo prdx qsox selenop shbg tf thb uchl vtn azgp serpina may combined various combination example one embodiment combination marker found high diagnostic power auc showed auc separate set validation set independent data indicating good diagnostic power one embodiment combination marker early diagnosis liver cancer highrisk group includes alb apob apol btd cdh cat cetp esyt afp fga gp g serpina itih itih serpina lum mpo pon pvr saa serpina apob cat cetp c afp fetub fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina lrg apoc cetp afp serpina tf serpina apoc afp serpina lmnb mpo pvr serpina serpina apob cat cetp afp fetub fga g serpina itih serpina uba shbg f thb thb serpina cetp c afp ilrap serpina lgalsbp mpo hdlbp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpinaitih serpina prdx selenop shbg thb uchl serpina alb apob ca cetp afp fetub serpina itih serpina mpo f thb serpina also combination present marker used early diagnosis liver cancer hepatitis b patient among highrisk group liver cancer one embodiment comparison hepatitis group liver cancer group least one marker selected alb igfals serpinc apoa apoa apob apoc apoc apoh apom bco cdh ca ca cat cetp bche c ppbp f fabp fcgbp fcn afp fetub fga ilrap itih itih serpina kng lgalsbp pro proz psmd qsox sa vcam serpina serpina may combined various combination example one embodiment combination marker found high diagnostic power auc showed auc separate independent data set validation set indicating good diagnostic power embodiment comparison hepatitis group liver cancer group least one marker selected alb igfals apob apoc bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp pro psmd vcam serpina may combined various combination example one embodiment combination marker found high diagnostic power auc showed auc separate independent data set validation set indicating good diagnostic power one embodiment combination marker includes igfals apoa c ppbp f fabp fcgbp afp itih serpina serpina igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb igfals cetp c ppbp fabp afp ilrap itih itih serpina sa serpina | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 18 | alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina igfals ca cetp c ppbp fabp fcgbp fcn afp fga itih serpina serpina igfals serpinc apoa cat c ppbp f fcgbp afp fga itih serpina proz qsox serpina apob apoc apoh cdh ppbp fabp afp fetub serpina serpina apob apoc apoh apom cat ppbp fabp afp fetub itih serpina serpina also combination present marker used early diagnosis liver cancer liver cirrhosis patient among highrisk group liver cancer embodiment comparison liver cirrhosis group liver cancer group least one marker selected apob apol cat cetp c fabp afp fga fn ighm serpina itih serpina pon serpina bco cfh bche selenop uchl azgp ambp apom crl clu ppbp hspb f g rbp hdlbp apoa fgb serpind lum qsox shbg c fbln serpinf f ca c may combined various combination example one embodiment combination marker found high diagnostic power auc showed auc separate independent data set validation set indicating good diagnostic power embodiment comparison liver cirrhosis group liver cancer group least one marker selected apoa apob bco crl cat cetp cfh bche afp fga fgb serpind serpina serpina lum qsox selenop shbg uchl azgp serpina may combined various combination example one embodiment combination marker found high diagnostic power auc showed auc separate independent data set validation set indicating good diagnostic power one embodiment combination marker includes apob apol cat cetp c fabp afp fga fn ighm serpina itih serpina pon pon serpina bco cat cetp cfh bche afp fga serpina selenop uchl azgp serpina ambp apob apom crl cat cetp clu ppbp hspb f fga g serpina serpina rbp hdlbp azgp serpina apoa apob crl cetp afp fgb serpind serpind serpina serpina lum qsox shbg serpina apoa apob apol cetp c fbln afp fga serpina itih serpina serpinf apob cetp fbln afp fga fga serpina rbp hdlbp serpina apob cetp afp fga serpina serpina f serpina apoa apob apob apol ca cetp clu c afp fga serpina itih serpina azgp serpina embodiment least one marker present disclosure may used combination afp marker according present disclosure detected analyze presence absence marker andor expression level difference expression level change expression level mrna andor protein level various quantitative andor qualitative analysis method known art term detection detecting used herein refers determination quantity quality andor change expression pattern andor profile expression detection includes determination presence andor absence well level present marker present marker may detected using method known art person skilled art would easily able select appropriate method detection detection marker according present disclosure may based functional andor antigenic characteristic thereof one embodiment present marker detected using agent specifically interact marker nucleic acid level particularly mrna level andor protein level agent detect activity function marker may also used quantitative qualitative analysis marker according present disclosure various known method qualitatively quantitatively detecting protein nucleic acid used quantitative qualitative analysis method protein level may include example western blot elisa radioimmunoassay immunodiffusion immunoelectrophoresis immunostaining immunoprecipitation complement fixation assay assay binding labelled antibody solutionsuspension mass spectrometry protein array employing antibody like quantitative qualitative analysis method nucleic acid level may include example nucleic acid transcription amplification system etag system system based tailed bead array system nucleic acid array like method known art may found example chipbased capillary electrophoresis colyer et al j chromatogr mass spectroscopy petricoin et al lancet etag system chanhui et al clinical immunology microparticleenhanced nephelometric immunoassay montagne et al eur j clin chem clin biochem like one embodiment present disclosure mass spectrometry used detecting present marker may performed using method described example present disclosure kim et al j proteome re anderson l et al mol cell proteomics may also referred one embodiment multiple reaction monitoring mrm technology utilizing example triple quadrupole lcmsms qtrap like ion directed quadruple anode consisting four electrode line analyzed according mass charge z ratio may used refer fig mrm method exactly quantifying multiple marker present biological sample minute amount mrm first mass filter q passing peptide particular mz parent precursor ion selected ion fragment generated ionization source transferred collision cell q precursor ion arrived collision cell collide internal collision gas fragmented product daughter ion transferred second mass filter q | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
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1710.06481 | 19 | peptide specific mz selected delivered detector convert digital signal generates peak chromatogram way mrm information desired target obtained high selectivity sensitivity peptide analyzed part entire protein sequence analyzed used mrm analysis optimal target peptide analyzed may selected entire sequence protein satisfies certain condition representativeness protein analyzed whether modified length suitable mrm analysis like example peptide amino acid length selected length short selectivity lowered length long sensitivity lowered addition methionine cysteine tryptophan easily chemically modified oxidation thus excluded addition mrm us internal standard corresponding peptide interest internal standard amino acid sequence target peptide described mass one amino acid constituting internal standard differs amino acid mass peptide interest however amino acid sequence hydrophobicity identical internal standard peptide elute retention time peptide interest way confirmed whether target peptide actually derived target protein one embodiment present disclosure detection marker according present application carried detection corresponding peptide marker protein example corresponding target peptide marker described table one peptide may used one protein marker one embodiment present disclosure least one amino acid constituting internal standard material peptide may labeled radioactive isotope c n mixture thereof sable isotopelabeled peptide internal standard peptide si peptide example gillette et al nature method may referred since amount internal standard added sample possible normalize entire analysis result verify whether target peptide detected actually derived protein analyzed one embodiment multiple simultaneous quantitative analysis mrm used detection marker according present invention us mass spectrometry target peptide sample detection specific peptide ion use internal standard calculation ratio relative absolute concentration change thus able quantify amount particular protein peptide physiological state method according present invention mrm analysis may performed monitoring q q value internal standard peptide interest may select use q q pair showing highest signal embodiment immunoassay using sandwich system like elisa enzyme linked immuno sorbent assay ria radio immuno assay like may used quantitative andor qualitative detection present marker system biological sample reacted first antibody fixed solid substratesupport glass plastic example polystyrene polysaccharide bead nylon nitrocellulose membrane microplate well form complex complex allowed react second antibody usually labeled agent detected directly indirectly radioactive substance like h fluorescent material chemiluminescent substance hapten biotin digoxygenin like case labeling material conjugated enzyme horseradish peroxidase alkaline phosphatase maleate dehydrogenase able produce color color change illuminate presence appropriate substrate method based immune reaction may also used embodiment immuno electrophoresis ouchterlony plate western blot crossed ie rocket ie fused rocket ie affinity ie detect marker simply antigenantibody reaction may used agent material may used method described known art may found enzyme immunoassay e maggio ed crc press boca raton florida gaastra w enzymelinked immunosorbent assay elisa method molecular biology vol walker jm ed humana press nj intensity signal generated immunoassay mentioned analyzed namely compared signal appropriate control determination whether sample disease agent material used method known art example monoclonal antibody polyclonal antibody substrate aptamer avimer peptidomimetic receptor ligand cofactor specifically interact present marker may used agent material bind interact specifically marker present disclosure utilized mean chip nanoparticles detecting agent may also labeled direct indirect signal detection via sandwich form case direct labeling method biological sample serum used array may labeled fluorescent material cy cy case indirect labeling unlabeled sample allowed bind detecting agent attached array target marker protein detected labeled antibody specifically recognize marker target case sandwich method sensitivity specificity detection usually high able detect marker | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 20 | pgml level addition labeling agent including radioactive material agent produce visible color proper condition magnetic particle highdensity electron particle like may also used detection fluorescence signal scanning confocal microscopy may used available example affymetrix inc agilent technology inc like composition present disclosure may also include one additional component needed detection present marker include example binding buffer reagent preparing biological sample syrinx blood collecting negative andor positive control composition present disclosure various agent described may contained may provided elisa dip stick rapid kit mrm microarray gene amplification immunoassay reagent may included particular kitcomposition may appropriately selected known agent view present disclosure one embodiment elisa dip stick rapid kit used case antibody detect present marker may provided conjugated substratesupport example well multiwell plate surface glass slide nitrocellulose paper dip stick form widely used poct point care technology biomarkers present disclosure may detected employing one antibody conjugated substrate nitrocellulose paper contacted sample serum example dipping one end stick serum sample moved substrate capillary action marker detected color developed marker interest bound antibody attached substrate embodiment mrm kit based peptide analysis provided mrm analysis may performed used described mrm method using peptide selectively recognize particular protein detect marker biological sample stable manner compared existing method employ antibody sensitive environmental condition temperature humidity like example peptide may employed listed table one peptide per marker may used aspect detecting agent may used present disclosure may provided type array microarray chip detecting agent may attached surface substrate glass nitrocellulose reference array preparation technology may found example schena et al proc natl acad sci usa schena et al science u pat no detecting agent provided attached array include limited antibody specifically recognizing present marker antibody fragment aptamers avimers avidity multimer peptidomimetics aspect present disclosure related method early diagnosis surveillance liver cancer subject highrisk developing cancer using marker combination marker disclosed herein still aspect present disclosure related method detecting marker combination marker disclosed herein early diagnosis surveillance liver cancer subject highrisk developing cancer method particularly performed vitro still aspect present disclosure related method detecting marker combination marker disclosed herein provide information early diagnosis surveillance liver cancer subject highrisk developing cancer reference may made marker combination marker employed various method according present disclosure described one embodiment present method early diagnosis surveillance liver cancer subject highrisk developing cancer present method comprises step detecting blood sample subject need thereof presence absence andor concentration nucleic acid andor protein one biomarkers selected group consisting orm alphaacid glycoprotein serpina alphaantitrypsin serpinf alphaantiplasmin alphamacroglobulin alb serum albumin serpinc antithrombiniii apoa apolipoprotein ai apoa apolipoprotein aiv apob apolipoprotein b apoc apolipoprotein ciii apoc apolipoprotein civ apof apolipoprotein f apoh betaglycoprotein apol apolipoprotein l apom apolipoprotein bco betabetacarotene oxygenase btd biotinidase crl complement cr subcomponentlike protein cdh cadherin ca carbonic anhydrase ca carbonic anhydrase cat catalase cpb carboxypeptidase b cetp cholesteryl ester transfer protein cfh complement factor h c complement c cb complement component c beta chain c complement component c ppbp platelet basic protein hspb endoplasmin entpd ectonucleoside triphosphate diphosphohydrolase esyt extended synaptotagmin f coagulation factor vii f coagulation factor ix fabp fatty acidbinding protein liver fcgbp iggfcbinding protein fetub fetuinb fga fibrinogen alpha chain fgb fibrinogen beta chain rack receptor activated protein c kinase gp platelet glycoprotein v g glutathione synthetase serpind heparin cofactor icam intercellular adhesion molecule ighm immunoglobulin heavy constant mu ilrap interleukin receptor accessory protein itih interalphatrypsin inhibitor heavy chain h itih interalphatrypsin inhibitor heavy chain h kng kininogen lmnb laminb mpo myeloperoxidase pon serum paraoxonasearylesterase prdx peroxiredoxin proc vitamin kdependent protein c pro vitamin kdependent protein proz vitamin kdependent protein z psmd proteasome nonatpase regulatory subunit pvr poliovirus receptor rbp retinolbinding protein sa protein sa saa serum amyloid protein uba sumoactivating enzyme subunit selenop selenoprotein p sparc sparc tf serotransferrin thb thrombospondin uchl ubiquitin carboxylterminal hydrolase isozyme l vcam vascular cell adhesion protein hdlbp vigilin | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 21 | vim vimentin azgp zincalphaglycoprotein serpina protein zdependent protease inhibitor lrg leucinerich alphaglycoprotein igfals insulinlike growth factorbinding protein complex acid labile subunit ambp protein ambp cleaved alphamicroglobulin bche cholinesterase clu clusterin cndp betaalahis dipeptidase c complement component c c complement component c fbln fibulin fcgra low affinity immunoglobulin gamma fc region receptor iiia fcn ficolin afp alphafetoprotein fn fibronectin igfbp insulinlike growth factorbinding protein igf insulinlike growth factor ii jchain immunoglobulin j chain serpina plasma serine protease inhibitor itih interalphatrypsin inhibitor heavy chain h serpina kallistatin klkb plasma kallikrein lcat phosphatidylcholinesterol acyltransferase lgalsbp galectinbinding protein lum lumican plg plasminogen qsox sulfhydryl oxidase shbg sex hormonebinding globulin f prothrombin gc vitamin dbinding protein vtn vitronectin comparing result detection presence absence amount nucleic acid protein corresponding marker control sample determining subject liver cancer wherein change amount andor presence absence biomarker nucleic acid andor protein level subject control sample indicates subject liver cancer one embodiment marker selected group consisting orm serpina serpinf alb serpinc apoa apoa apob apoc apoc apof apoh apol apom bco btd crl cdh ca ca cat cpb cetp cfh c complement c cb c ppbp hspb entpd esyt f f fabp fcgbp fetub fga fgb rack gp g serpind icam ighm ilrap itih itih kng lmnb mpo pon prdx proc pro proz psmd pvr rbp sa saa uba selenop sparc tf thb uchl vcam hdlbp vim azgp serpina embodiment marker may comprise least one marker selected group consisting lrg igfals ambp bche clu cndp c c fbln fcgra fcn afp fn igfbp igf jchain serpina itih serpina klkb lcat lgalsbp lum plg qsox shbg f gc vtn method according present invention may also used one embodiment surveillance early diagnosis liver cancer onset among high risk group liver cancer particular cirrhosis patient embodiment surveillance liver cancer development early diagnosis liver cancer onset especially hepatitis b patient marker reference may made foregoing marker used method according invention also used combination two reference foregoing method according invention method detecting quantifying one marker referred foregoing method mass spectrometry particular mrm analysis microarrays especially protein microarrays nucleic acid amplification example nucleic acid amplification synthesizing mrna cdna various immunoassay method elisa used one embodiment method according present disclosure carried mrm analysis method mrm reference may made foregoing peptide marker used mrm listed table blood used sample protein sample depleted degraded treated proteinase example trypsin example method according present invention peak area derived mrm analysis target peptide using software skyline normalized analysis result internal standard detect amount present marker sample amount marker along detected peak area target peptide sample divided peak area standard internal peptide calculate amount present marker control sample employed present method sample hepatitis b andor liver cirrhosis patient thus early diagnosis liver cancer using marker according present application diagnose patient progressing hepatitis b liver cirrhosis liver cancer advantageous surveillance especially early diagnosis step determining whether subject cancer present method change expression level increase decrease depending particular marker present marker comparison control described indicate subject early stage liver cancer marker according present invention marker expression increased early stage liver cancer comparison control follows ighm c hspb jchain esyt g cat uchl pvr apob fbln ca itih prdx fcgra qsox fabp ca fga lgalsbp cdh bco icam c vim serpina fcgbp afp shbg vcam serpina marker according present invention marker expression decreased early stage liver cancer comparison control follows clu cpb klkb gp proc thb rbp igfbp ppbp gc fcn bche entpd alb serpind pro sparc f kng fgb mpo cetp plg serpinf lrg cb lcat igf fetub fn apoh saa selenop serpina f tf orm rack itih c igfals apoc apom lum apol fga azgp ilrap lmnb vtn cndp serpinc pon apoc proz crl cfh apof apoa c serpina uba itih apoa btd hdlbp ambp sa psmd f biological sample sample used composition kit method according present invention blood sample whole blood serum plasma one embodiment herein serum sample particular used biological sample used composition kit method according present invention obtained mammal particularly human human subject include develop hepatitis cirrhosis cirrhosis need monitorsurveillance liver cancer development early diagnose liver cancer embodiment method may performed determine whether liver cancer present | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 22 | subject symptom related liver disease abdominal pain hypertrophy ascites jaundice muscle weakness esophageal varix two marker present disclosure used combination dataset may generated includes profile ie quantitative information related expression marker protein sample obtaining profile marker tested comparison result reference group control group determines whether subject sample develops liver cancer method known art used compare marker profile control group test group using sample example digital image comparison expression profile comparison expression data using db u may referred profile obtained detecting marker according present disclosure processed using data analysis method known related art example nearest neighbor classifier partialleast square svm adaboost clusteringbased classification method example bendor et al j comput biol nguyen et al bioinformatics wang et al bmc bioinformatics liu et al genome inform ser workshop genome inform yeang et al bioinformatics suppl xiong biotechniques like may referred addition various statistical processing method may used determine quantification result obtained detecting marker present application significant discriminate early liver cancer one embodiment logic regression method used statistical processing method ruczinski journal computational graphical statistic may referred analysis method may used present disclosure may includes nearest shrunken centroid tibshirani pnas random forest breiman machine learning mart hastie element statistical learning springer one embodiment statistical processing may determine level confidence significant difference result obtained subjectderived sample control group diagnosis liver cancer raw data used statistical processing value analyzed duplicate triple multiple marker another embodiment method may performed several time period time example year may used monitor trend expression pattern increase decrease expression marker monitored correlate early liver cancer change used determine early diagnosis progression exacerbation alleviation liver cancer compared previous test value subject value control group based change marker expression time preventive measure taken prevent progression liver cancer severe liver cancer conjunction use method according present invention confirmation liver cancer method according present invention may used example accompanied conventional blood marker afp examination ultrasound computerized axial tomography ct scan magnetic resonance imaging mri one embodiment subject determined early stage liver cancer using marker according present application cancer confirmed detailed examination mri andor petct appropriate treatment performed present disclosure explained detail reference following example example however interpreted limiting scope present invention manner exmaples example information clinical sample used present disclosure serum sample total patient used analysis patient include patient confirmed liver cancer patient high risk developing liver cancer hepatitis b liver cirrhosis patient approved institutional review board seoul asan medical center irb approval serum collected centrifugation min c rpm immediately taking blood sample patient serum stored c l aliquot use analysis patient group highrisk developing liver cancer patient group confirmed liver cancer diagnosed asan medical center year age confirmed good liver function childpugh class case liver cancer patient patient extremely early stage liver cancer tumor le cm size determined imaging examination ct mri biopsy selected patient highrisk developing liver cancer patient diagnosed chronic hepatitis b liver cirrhosis without history liver cancer determined imaging examination blood test selected total serum sample received three incidence one hundred fifty sample first received includes sample hepatitis b patient liver cirrhosis patient liver cancer patient second batch total sample include sample hepatitis b patient liver cirrhosis patient liver cancer patient third batch total sample includes sample hepatitis b patient liver cirrhosis patient liver cancer patient clinical information patient sample collected disclosed table example screening biomarker example selection target marker candidate protein liveratlas database protein human protein atals currently comprehensive resource associated liver disease selected also protein selected proteome profiling using pair normal hcc tissue protein approved food drug administration fda laboratory developed test ldt protein | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 23 | maker diagnosis liver cancer previously developed included thus total protein selected among protein secretory protein quantitative analysis using blood selected using prediction tool plasma proteome database targetp signalp secretomep go annotation exocarta tmhmm prediction uniprot db candidate reviewed bioinformatical analysis curator paper using uniprotkb database total candidate selected public spectral library isb nist swathatlas homemade serumtissue spectrum library used select final candidate peptide msms data thus analyzed mass spectrometry resulting total protein peptide derived therefrom final candidate example screening detectable marker target candidate candidate protein peptide therefrom described example protein technical reproducibility well expression pattern different among liver cirrhosis group hepatitis group liver cancer group selected sample first batch pooled group hepatic cancer patient cirrhosis patient hepatitis b patient respectively sample prepared pretreated made peptide used mrm analysis using qqq mass spectrometer agilent inc described example mrm analysis performed time set criterion selecting peptide detectable target follows whether peak detected within minute expected retention time whether transition observed rt whether dot product dotp score indicating probability detected peak indeed predicted protein higher based criterion total protein total peptide selected example screening quantifiable marker target candidate semiquantitative mrm analysis using sample protein peptide derived therefrom selected example performed select quantifiable marker candidate surveillance monitoringdiagnosis highrisk group developing liver cancer using mrm platform random number generated total sample patient hcc patient cirrhosis lc patient hepatitis b hbv divided batch sample batch adjusted similar percentage sample group semiquantitative mrm analysis performed serum sample filter target synthesized high purity semiquantitative mrm analysis performed using irt indexed retention time kit biognosys inc consists nonnaturally occurring synthetic peptide performing following comparison experiment comparison hepatitis b group hbv liver cancer group hcchbv v hcc comparison liver cirrhosis group lc liver cancer group hcc lc v hcc comparison hepatitis b group hbv liver cirrhosis group lc hbv v lc comparison group highrisk developing cancer hepatitis b liver cirrhosis hbvlc liver cancer group hcc hbvlc v hcc peptide auc peptide auc le selected resulting protein peptide next si stable isotopelabeled synthetic peptide used internal standard peptide corresponding endogenous peptide labeled stable radioisotope corresponding protein peptide used confirm selected protein peptide actually present blood using mrm assay described sample pooled liver cancer patient liver cirrhosis patient hepatitis patient respectively peak area target peptide mrm assay divided corresponding peak area internal standard peptide normalization fmol si peptide injected detect corresponding endogenous peptide result protein peptide detected check signal interference peptide target endogenous peptide complex blood sample mrm assay protein peptide product ion q intensity pattern si peptide blood endogenous peptide obtained time sample pooled liver cancer patient liver cirrhosis patient hepatitis patient respectively determine whether signal interference present audit automated detection inaccurate imprecise transition used compare relative intensity product ion si peptide endogenous peptide blood pvalue threshold confirmed whether peak area peptide blood si peptide constantly detected repeated measurement cv threshold result total endogenous protein peptide derived therefrom show signal interference target peptide thus rendering accurate quantification selected final marker candidate exmaple mrm analysis exmaple pretreatment clinical serum sample digestion serum protein make peptide discover marker blood found low concentration high abundant six protein ie albumin igg iga haptoglobin transferrin alphaantitrypsin blood depleted depletion process mass total protein present blood removed protein corresponding rest used next analysis depletion performed using mar multiple affinity removal system agilent usa column according manufacturer instruction serum sample treated depletion process concentrated concentration measured bca bicinchoninic acid method g serum sample treated rapigest water mm dtt nm abc buffer tris ph incubated c min sample treated iaa | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 24 | final concentration mm incubated min rt sample treated trypsin concentration ratio trypsin serum sample treated fa incubated c hr centrifuged rpm c hr obtain supernatant example internal standard peptide si peptide stableisotope labeled standard used internal standard peptide labelled heavy isotope synthesized jpt inc germany si peptide c n lysin lys k arginine arg r cterminus peptide substituted c n respectively si peptide different corresponding endogenous peptide mass amino acid sequence hydrophobicity corresponding endogenous peptide thus eluted rt chromatogram si peptide used adding serum peptide sample concentration fmol normalization confirmation endogenous peptide detection exampe quantification using mrm analysis capillary lc system agilent technology santa clara ca two pump coupled triple quadrupole qqq mass spectrometer agilent jetstream electrospray source used mrmms analysis liquid chromatography used perform desalting peptide separation mobile phase water v v formic acid mobile phase b acetonitrile v v formic acid l sample analyzed injected analytical column passing guard column flow rate used l min injected sample passed guard column agilent zorbax stablebond c mm bar desalted first id fractionated first fractionated peptide nd fractionated eluted passing analytical column agilent zorbax eclipse sbc mm mm mobile phase mobile phase b peptide eluted mobile phase b formic acid acetonitrile min concentration gradient minute mass spectrometry used monitor mrm mode transition eluted peptide gas temperature c gas flow used l min nebulizer psi sheath gas temperature c sheath gas flow used l min capillary voltage nozzle voltage used v v respectively resolution quadruple q quadruple q set unit dwell time set total cycle time sec retention time eluted selected peptide analyzed based analysis performed scheduled mrm method window size min example mrm data analysis data obtained example used select peptide fragment ion mrm analysis using skyline skyline open source software mrm method development analysis stergachis ab et al nat method mrm analysis raw data file produced mass spectrometer imported skyline program aligned quantify feature savitzkygolay method applied smooth data point mrmms analysis result visually examined calculate peak area transition relative abundance compared using peak area normalized internal standard peptide si peptide example statistical analysis order identify biomarkers different expression levelspatterns highrisk developing liver cancer hepatocellular carcinoma group univariable analysis multivariable analysis performed evaluate marker following group consisting comparison control group high risk group hbvlc v liver cancer group hcc hepatitis b group hbv v liver cancer group hcc liver cirrhosis group lc v liver cancer group hcc firstly univariable analysis peptide protein candidate marker analyzed three group logistic regression analysis performed three experiment analysis result evaluated efficacy present marker using roc receiver operator characteristic roc curve represents sensitivity specificity change relationship twodimensional plane larger auc area curve value corresponding area roc better diagnostic method marker auc selected herein marker showing difference expression comparisoncontrol group secondly multivariable analysis peptide protein candidate marker analyzed three group first second experiment integrated used analytical data result third experiment used verify result multivariate analysis analytical method logistic regression support vector machine used two kind resampling method used reference prior art crossvalidation method set fold fold analysis referring kim h et al sci rep aug kim h et al mol cell proteomics jul analyzed setting fold fold prior art meyers rl et al lancet oncol jan bootstrap method analyzed dividing analysis data ratio referring meyers rl et al lancet oncol jan roc curve accuracy used confirm diagnostic power accuracy multivariate analysisbased model selected multiple marker combination auc marker influence distinction liver cancer group control statistical analysis performed using spss ver ibm usa r ver example biomarkers finally identified example identification | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 25 | marker early diagnosis liver cancer applying real individual sample one hundred seventyseven protein target marker peptide therefrom described example tested sample asan medical center mrm analysis pretreatment clinical sample mrm analysis order injecting sample mass spectrometer experimental design blinding randomization batch established first batch experiment mrm analysis done blood sample total subject hepatitis b cirrhosis liver cancer patient second batch experiment mrm analysis done blood sample total subject hepatitis b cirrhosis liver cancer patient third batch experiment mrm analysis done blood sample total subject hepatitis b cirrhosis liver cancer patient mrm analysis performed basically way described example briefly analysis done using triple quadrupole qqq mass spectrometer agilent technology usa equipped jetstream electrospray coupled capillary lc system agilent consisting two pump data mrm analyzed skyline final marker identified univariable analysis multivariable analysis protein selected example peptide derived therefrom univariate analysis liver cancer group compared high risk group hbv lc hepatitis b group hbv liver cirrhosis group lc evaluate confirm difference expression pattern individual diagnostic power single marker final marker determined univariate multivariate analysis identified marker candidate group univariate multivariate analyzes described example respectively whereby final identified marker described table described auc value expressed mean value example identification marker univariable analysis protein peptide selected example applied individual sample derive marker used single marker liver cancer group compared highrisk group hbv lc hepatitis b group hbv cirrhosis group lc change expression pattern individual marker compared control determined hepatic cancer surveillance diagnostic marker candidate protein peptide analyzed logistic regression three comparative group hepatitis b v liver cancer cirrhosis v liver cancer hepatitis b liver cirrhosis v liver cancer using auc value roc curve single marker differ comparison group identified statistical analysis performed using spss ver ibm usa r ver marker candidate surveillance diagnosing liver cancer selected marker showed difference expression comparison expression pattern auc first second third experiment three comparison group refer table result total protein peptide therefrom showed differential expression highrisk group developing liver cancer comparison liver cancer group identifiedselected listed table among marker described particularly peptide marker found differentially expressed comparison group hepatitis b v hcc listed table among marker peptide peptide protein showed higher expression liver cancer group peptide protein showed higher expression hepatitis b group particular protein vcam c igfals clu ppbp serpind confirmed auc three experiment among vcam c highly expressed liver cancer group igfals clu ppbp serpind highly expressed hepatitis b group among marker particular cirrhosis group lc v hcc comparison identified six peptide five protein apob afp serpina cetp mpo auc three experiment shown table marker apob afp serpina highly expressed liver cancer group two marker cetp mpo confirmed highly expressed cirrhosis group among marker particular liver cancer high risk group hbv lc v liver cancer group hcc comparison identified four peptide four protein afp serpina cetp fetub auc three experiment shown table afp serpina highly expressed liver cancer group cetp fetub highly expressed liver cancer high risk group afp highly expressed liver cancer group auc first experiment cetp fetub serpina identified third experiment serpina showed high discrimination ability auc third experiment liver cancer high risk group hepatitis group cirrhosis group analyzed integrating data two disease group clinically hepatitis b also cause liver cirrhosis sample used study may also include sample patient progressed liver cirrhosis hepatitis b however case hepatitis b progress directly liver cancer therefore even hepatitis progress cirrhosis cirrhosis include hepatitis cirrhosis represent condition hepatitis past represent current cirrhosis marker described advantageously used early diagnosis liver cancer subject hepatis subject chronic hepatitis diagnosed cirrhosis example identification marker | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 26 | multivariable analysis three comparison group hepatitis b v liver cancer cirrhosis v liver cancer hepatitis b cirrhosis v liver cancer multivariate analysis performed time peptide protein maker liver cancer surveillance confirm cause effect relationship multiple marker combination multiple marker cause effect relationship single marker multivariate analysis data combine first second experiment used prevent confounding effect various variable third experimental data used independent data verify multivariate analysisbased model derived first second experimental result model combination marker influential development liver cancer multivariate analysis distinguish liver cancer group control group depending analysis method marker affecting result may selected combined differently compensate two kind method ie logistic regression support vector machine used model selected combined multivariate analysis distinguish liver cancer group control group higher diagnostic power accuracy single marker however model made using given data may possibility model produce good result current data set bad result new data set reason overfitting solve problem resampling method used reference kim h et al sci rep aug kim h et al mol cell proteomics jul present model multivariate analysis validated using crossvalidation method fold fold reference meyers r let al lancet oncol jan present model multivariate analysis validated bootstrap method split data ratio finally roc curve accuracy used confirm diagnostic power accuracy multivariate analysisbased model statistical analysis performed using spss ver ibm usa r ver result multivariate analysis confirmed present model combination multiple marker cause effect relationship including single marker showing differential expression comparison liver cancer group distinguish liver cancer group control group improved diagnostic power compared single marker one embodiment present disclosure marker candidate liver cancer surveillance diagnosis marker combined auc determined two analytical method resampling method refer table result total protein peptide derived therefrom selected combined model distinguishing liver cancer group highrisk group shown table example generation multiple marker combination using selected marker multivariate analysis list marker selected example see table model combination multiple marker developed based auc accuracy value determined logistic regression support vector machine liver cancer high risk group hepatitis cirrhosis v liver cancer group cirrhosis group v liver cancer group hepatitis b group v liver cancer group two resampling method two analytical method three comparison group model combination marker influential development liver cancer auc developed among crossvalidation used model multiple marker combined identified auc shown table bootstrap used model multiple marker combined identified auc shown table table model showing highest auc accuracy among model multiple marker combined two analysis method model combination marker auc accuracy logistic regression method model combination marker auc accuracy support vector machine method third set validation set marker combination model logistic regression identified auc accuracy marker combination model support vector machine validated auc accuracy marker cetp fga serpina mpo serpina shbg alb apob afp itih serpina pvr fetub tf f thb commonly combined two analytical method logistic regression support vector machine combination marker disclosed table table highrisk liver cancer group liver cancer group hbv lc v hcc compared protein peptide determined combinable marker list marker used combination shown table combination marker disclosed table cirrhosis group lc liver cancer group hcc lc v hcc compared protein peptide determined combinable marker list marker used combination shown table marker combined among marker listed table table showed excellent diagnostic power auc thus third data validation set confirmed cat apol rbp hdlbp azgp cetp fga apob serpina serpina serpina apoa afp itih commonly combined logistic regression support vector machine method model highest auc accuracy among model multiple marker two analysis method model auc accuracy logistic regression marker combined model marker combination auc | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 27 | accuracy support vector machine third set validation set auc value accuracy value marker combination model logistic regression marker combination model support vector machine respectively verifying diagnostic power accuracy present model combination marker disclosed table hepatitis group hbv liver cancer group hcc hbv v hcc compared protein peptide determined combinable marker list marker used combination shown table table marker apob cetp afp itih serpina serpina cat igfals c ppbp fabp fcgbp itih combined common two algorithm logistic regression support vector machine among model multiple marker combined two analysis method model highest auc accuracy model auc accuracy marker logistic regression model auc accuracy marker support vector machine two model validated third set validation set marker combination model validated auc accuracy respectively marker combination model showed auc accuracy respectively proved diagnostic power accuracy multiple marker combination listed table combination list marker multivariate based model whose diagnostic power auc accuracy verified auc validation set shown table result multivariate analysis confirmed combination multiple marker rather individual single marker improve diagnostic power highrisk group liver cancer compared liver cancer group present invention using total serum sample protein peptide therefrom showing differential expression pattern comparison high risk liver cancer group hepatitis b hbv group liver cirrhosis lc group liver cancer hcc group identified marker combination marker advantageously used marker surveillance early diagnosis liver cancer highrisk liver cancer patient various singularplural permutation may expressly set forth herein sake clarity although embodiment present disclosure shown described would appreciated skilled art change may made embodiment without departing principle sprit invention scope defined claim equivalent unless defined interpreted otherwise technical scientific term acronym used herein meaning commonly understood one ordinary skill art field invention content publication disclosed reference herein incorporated herein reference claim biomarker monitoring early diagnosis liver cancer subject high risk developing liver cancer blood sample biomarker least one biomarker selected group consisting orm alphaacid glycoprotein serpina alphaantitrypsin serpinf alphaantiplasmin alphamacroglobulin alb serum albumin serpinc antithrombiniii apoa apolipoprotein ai apoa apolipoprotein aiv apob apolipoprotein b apoc apolipoprotein ciii apoc apolipoprotein civ apof apolipoprotein f apoh betaglycoprotein apol apolipoprotein l apom apolipoprotein bco betabetacarotene oxygenase btd biotinidase crl complement cr subcomponentlike protein cdh cadherin ca carbonic anhydrase ca carbonic anhydrase cat catalase cpb carboxypeptidase b cetp cholesteryl ester transfer protein cfh complement factor h c complement c cb complement component c beta chain c complement component c ppbp platelet basic protein hspb endoplasmin entpd ectonucleoside triphosphate diphosphohydrolase esyt extended synaptotagmin f coagulation factor vii f coagulation factor ix fabp fatty acidbinding protein liver fcgbp iggfcbinding protein fetub fetuinb fga fibrinogen alpha chain fgb fibrinogen beta chain rack receptor activated protein c kinase gp platelet glycoprotein v g glutathione synthetase serpind heparin cofactor icam intercellular adhesion molecule ighm immunoglobulin heavy constant mu ilrap interleukin receptor accessory protein itih interalphatrypsin inhibitor heavy chain h itih interalphatrypsin inhibitor heavy chain h kng kininogen lmnb laminb mpo myeloperoxidase pon serum paraoxonasearylesterase prdx peroxiredoxin proc vitamin kdependent protein c pro vitamin kdependent protein proz vitamin kdependent protein z psmd proteasome nonatpase regulatory subunit pvr poliovirus receptor rbp retinolbinding protein sa protein sa saa serum amyloid protein uba sumoactivating enzyme subunit selenop selenoprotein p sparc sparc tf serotransferrin thb thrombospondin uchl ubiquitin carboxylterminal hydrolase isozyme l vcam vascular cell adhesion protein hdlbp vigilin vim vimentin azgp zincalphaglycoprotein serpina protein zdependent protease inhibitor biomarker claim wherein biomarker comprises least one biomarker selected group consisting lrg leucinerich alphaglycoprotein igfals insulinlike growth factorbinding protein complex acid labile subunit ambp protein ambp cleaved alphamicroglobulin bche cholinesterase clu clusterin cndp betaalahis dipeptidase c complement component c c complement component c fbln fibulin fcgra low affinity immunoglobulin gamma fc region receptor iiia fcn ficolin afp alphafetoprotein fn fibronectin igfbp insulinlike growth factorbinding protein igf insulinlike growth factor ii jchain immunoglobulin j chain serpina plasma serine protease inhibitor itih interalphatrypsin inhibitor heavy chain h serpina kallistatin klkb plasma kallikrein lcat phosphatidylcholinesterol acyltransferase lgalsbp galectinbinding protein lum lumican plg plasminogen qsox sulfhydryl oxidase shbg sex hormonebinding globulin f prothrombin gc vitamin dbinding protein vtn vitronectin biomarker claim wherein subject high risk developing liver cancer includes hepatitis patient liver cirrhosis patient biomarker one claim wherein biomarker least one biomarker selected group consisting | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 28 | serpina alb apob apoc apoc apol btd cdh ca cat cetp c esyt fcgbp fetub fga gp g serpind ilrap itih lmnb mpo pon prdx pvr saa uba selenop tf thb uchl hdlbp azgp serpina biomarker claim wherein biomarker comprises least one biomarker elected group consisting lrg c afp jchain serpina serpina lgalsbp lum qsox shbg f vtn biomarker one claim wherein subject high risk developing liver cancer hepatitis patient least one biomarker monitoring early diagnosis liver cancer hepatitis patient selected group consisting orm alb serpinc apoa apoa apob apoc apoc apof apol apom apoh bco cdh cpb ca ca cat cetp cb ppbp f fabp entpd f fcgbp fetub fga rack gp serpind icam igf ilrap itih itih kng pon proc pro proz psmd rbp sa saa selenop sparc thb vcam vim serpina biomarker claim wherein biomarker comprises least one biomarker selected group consisting igfals bche clu cndp c fcgra fcn afp igfbp itih serpina klkb lcat lgalsbp plg qsox shbg f gc vtn biomarker one claim wherein subject high risk developing liver cancer liver cirrhosis patient least one biomarker monitoring early diagnosis liver cancer liver cirrhosis patient selected group consisting serpinf apoa apob apol apom bco crl ca cat cetp cfh c ppbp hspb f fabp fga fgb g serpind ighm itih mpo pon rbp selenop uchl hdlbp azgp serpina biomarker claim wherein biomarker comprises least one biomarker selected group consisting ambp bche clu c c fbln afp fn serpina serpina lum qsox shbg f biomarker one claim wherein least one biomarker combination biomarkers selected group consisting alb apob apol btd cdh cat cetp esyt afp fga gp g serpina itih itih erpina lum mpo pon pvr saa serpina apob cat cetp c afp fetub fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina lrg apoc cetp afp serpina tf serpina apoc afp serpina lmnb mpo pvr serpina serpina apob cat cetp afp fetub fga g serpina itih serpina uba shbg f thb thb serpina cetp c afp ilrap serpina lgalsbp mpo hdlbp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpina itih serpina prdx selenop shbg thb uchl serpina alb apob ca cetp afp fetub serpina itih serpina mpo f thb serpina biomarker one claim wherein subject high risk developing liver cancer hepatitis patient least one biomarker monitoring early diagnosis liver cancer hepatitis patient combination biomarkers selected group consisting igfals apoa c ppbp f fabp fcgbp afp itih serpina serpina igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb igfals cetp c ppbp fabp afp ilrap itih itih serpina sa serpina alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina igfals ca cetp c ppbp fabp fcgbp fcn afp fga itih serpina serpina igfals serpinc apoa cat c ppbp f fcgbp afp fga itih serpina proz qsox serpina apob apoc apoh cdh ppbp fabp afp fetub serpina serpina apob apoc apoh apom cat ppbp fabp afp fetub itih serpina serpina biomarker one claim wherein subject high risk developing liver cancer liver cirrhosis patient biomarker monitoring early diagnosis liver cancer liver cirrhosis patient combination biomarkers selected group consisting apob apol cat cetp c fabp afp fga fn ighm serpina itih serpina pon pon serpina bco cat cetp cfh bche afp fga serpina selenop uchl azgp serpina ambp apob apom crl cat cetp clu ppbp hspb f fga g serpina serpina rbp hdlbp azgp serpina apoa apob crl cetp afp fgb serpind serpina serpina lum qsox shbg serpina apoa apob apol cetp c fbln afp fga serpina itih serpina serpinf apob cetp fbln afp fga serpina rbp hdlbp serpina apob cetp afp fga serpina serpina f serpina apoa apob apol ca cetp clu c afp fga serpina itih serpina azgp serpina biomarker one claim wherein biomarker combination biomarker selected group consisting apob cat cetp c afp fetub fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpina itih serpina prdx selenop shbg thb uchl serpina biomarker one claim wherein subject high risk developing liver cancer hepatitis patient least one biomarker monitoring early diagnosis liver cancer hepatitis patient combination biomarkers selected group consisting igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina biomarker one claim wherein subject high risk developing liver cancer liver cirrhosis patient least one biomarker monitoring | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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] | ||
1710.06481 | 29 | early diagnosis liver cancer liver cirrhosis patient combination biomarkers selected group consisting bco cat cetp cfh bche afp fga serpina selenop uchl azgp serpina apoa apob crl cetp afp fgb serpind serpina serpina lum qsox shbg serpina biomarker one claim wherein blood sample plasma serum whole blood biomarker one claim wherein biomarker analyzed elisa assay using dipstick rapid kit mrm assay microarray assay nucleic acid amplification assay immunoassay biomarker claim wherein biomarker analyzed mrm assay wherein peptide biomarker used mrm assay one listed table method monitoring early diagnosis liver cancer subject high risk developing liver cancer comprising step detecting quantifying blood sample subject need thereof least one biomarker selected group consisting orm alphaacid glycoprotein serpina alphaantitrypsin serpinf alphaantiplasmin alphamacroglobulin alb serum albumin serpinc antithrombiniii apoa apolipoprotein ai apoa apolipoprotein aiv apob apolipoprotein b apoc apolipoprotein ciii apoc apolipoprotein civ apof apolipoprotein f apoh betaglycoprotein apol apolipoprotein l apom apolipoprotein bco betabetacarotene oxygenase btd biotinidase crl complement cr subcomponentlike protein cdh cadherin ca carbonic anhydrase ca carbonic anhydrase cat catalase cpb carboxypeptidase b cetp cholesteryl ester transfer protein cfh complement factor h c complement c cb complement component c beta chain c complement component c ppbp platelet basic protein hspb endoplasmin entpd ectonucleoside triphosphate diphosphohydrolase esyt extended synaptotagmin f coagulation factor vii f coagulation factor ix fabp fatty acidbinding protein liver fcgbp iggfcbinding protein fetub fetuinb fga fibrinogen alpha chain fgb fibrinogen beta chain rack receptor activated protein c kinase gp platelet glycoprotein v g glutathione synthetase serpind heparin cofactor icam intercellular adhesion molecule ighm immunoglobulin heavy constant mu ilrap interleukin receptor accessory protein itih interalphatrypsin inhibitor heavy chain h itih interalphatrypsin inhibitor heavy chain h kng kininogen lmnb laminb mpo myeloperoxidase pon serum paraoxonasearylesterase prdx peroxiredoxin proc vitamin kdependent protein c pro vitamin kdependent protein proz vitamin kdependent protein z psmd proteasome nonatpase regulatory subunit pvr poliovirus receptor rbp retinolbinding protein sa protein sa saa serum amyloid protein uba sumoactivating enzyme subunit selenop selenoprotein p sparc sparc tf serotransferrin thb thrombospondin uchl ubiquitin carboxylterminal hydrolase isozyme l vcam vascular cell adhesion protein hdlbp vigilin vim vimentin azgp zincalphaglycoprotein serpina protein zdependent protease inhibitor comparing result detection quantification control sample determining subject early stage liver cancer result changed comparison control method claim wherein biomarker comprises least one biomarker selected group consisting lrg leucinerich alphaglycoprotein igfals insulinlike growth factorbinding protein complex acid labile subunit ambp protein ambp cleaved alphamicroglobulin bche cholinesterase clu clusterin cndp betaalahis dipeptidase c complement component c c complement component c fbln fibulin fcgra low affinity immunoglobulin gamma fc region receptor iiia fcn ficolin afp alphafetoprotein fn fibronectin igfbp insulinlike growth factorbinding protein igf insulinlike growth factor ii jchain immunoglobulin j chain serpina plasma serine protease inhibitor itih interalphatrypsin inhibitor heavy chain hi serpina kallistatin klkb plasma kallikrein lcat phosphatidylcholinesterol acyltransferase lgalsbp galectinbinding protein lum lumican plg plasminogen qsox sulfhydryl oxidase shbg sex hormonebinding globulin f prothrombin gc vitamin dbinding protein vtn vitronectin method claim wherein subject high risk developing liver cancer includes hepatitis patient liver cirrhosis patient method one claim wherein least one biomarker selected group consisting serpina alb apob apoc apoc apol btd cdh ca cat cetp c esyt fcgbp fetub fga gp g serpind ilrap itih lmnb mpo pon prdx pvr saa uba selenop tf thb uchl hdlbp azgp serpina method claim wherein biomarker comprises least one biomarker selected group consisting lrg c afp jchain serpina serpina lgalsbp lum qsox shbg f vtn method one claim wherein subject high risk developing liver cancer hepatitis patient least one biomarker monitoring early diagnosis liver cancer hepatitis patient selected group consisting orm alb serpinc apoa apoa apob apoc apoc apof apol apom apoh bco cdh cpb ca ca cat cetp cb ppbp f fabp entpd f fcgbp fetub fga rack gp serpind icam igf ilrap itih itih kng pon proc pro proz psmd rbp sa saa selenop sparc thb vcam vim serpina method claim wherein biomarker monitoring early diagnosis liver cancer hepatitis patient comprises least one biomarker selected group consisting igfals bche clu cndp c fcgra fcn afp igfbp itih serpina klkb lcat lgalsbp plg qsox shbg f gc vtn method one claim wherein subject high risk developing liver cancer liver cirrhosis patient least one biomarker monitoring early diagnosis liver cancer liver cirrhosis patient selected group consisting serpinf apoa apob apol apom bco crl ca cat cetp cfh c ppbp hspb f fabp fga fgb g serpind ighm itih mpo pon qsox rbp selenop uchl hdlbp azgp serpina method claim wherein biomarker monitoring early diagnosis liver cancer liver cirrhosis patient comprises | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 30 | least one biomarker selected group consisting ambp bche clu c c fbln afp fn serpina serpina lum shbg f method one claim wherein least one biomarker combination biomarker selected group consisting alb apob apol btd cdh cat cetp esyt afp fga gp g serpina itih itih erpina lum mpo pon pvr saa serpina apob cat cetp c afp fetub fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina lrg apoc cetp afp serpina tf serpina apoc afp serpina lmnb mpo pvr serpina serpina apob cat cetp afp fetub fga g serpina itih serpina uba shbg f thb thb serpina cetp c afp ilrap serpina lgalsbp mpo hdlbp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpina itih serpina prdx selenop shbg thb uchl serpina alb apob ca cetp afp fetub serpina itih serpina mpo f thb serpina method one claim wherein subject high risk developing liver cancer hepatitis patient least one biomarker monitoring early diagnosis liver cancer hepatitis patient combination biomarkers selected group consisting igfals apoa c ppbp f fabp fcgbp afp itih serpina serpina igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb igfals cetp c ppbp fabp afp ilrap itih itih serpina sa serpina alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina igfals ca cetp c ppbp fabp fcgbp fcn afp fga itih serpina serpina igfals serpinc apoa cat c ppbp f fcgbp afp fga itih serpina proz qsox serpina apob apoc apoh cdh ppbp fabp afp fetub serpina serpina apob apoc apoh apom cat ppbp fabp afp fetub itih serpina serpina method one claim wherein subject high risk developing liver cancer liver cirrhosis patient least one biomarker monitoring early diagnosis liver cancer liver cirrhosis patient combination biomarkers selected group consisting apob apol cat cetp c fabp afp fga fn ighm serpina itih serpina pon pon serpina bco cat cetp cfh bche afp fga serpina selenop uchl azgp serpina ambp apob apom crl cat cetp clu ppbp hspb f fga g serpina serpina rbp hdlbp azgp serpina apoa apob crl cetp afp fgb serpind serpina serpina lum qsox shbg serpina apoa apob apol cetp c fbln afp fga serpina itih serpina serpinf apob cetp fbln afp fga serpina rbp hdlbp serpina apob cetp afp fga serpina serpina f serpina apoa apob apol ca cetp clu c afp fga serpina itih serpina azgp serpina method one claim wherein least one biomarker combination biomarker selected group consisting apob cat cetp c afp fetub fga fga gp serpind serpina itih serpina lgalsbp mpo qsox shbg tf vtn azgp serpina alb apob ca cetp c fcgbp afp fetub fga jchain serpina itih serpina prdx selenop shbg thb uchl serpina method one claim wherein subject high risk developing liver cancer hepatitis patient least one biomarker monitoring early diagnosis liver cancer hepatitis patient combination biomarkers selected group consisting igfals apob apoc ppbp fabp fcgbp afp itih serpina pro serpina alb apob bco cdh ca bche c ppbp fabp fcgbp afp fetub itih serpina kng lgalsbp psmd vcam serpina method one claim wherein subject high risk developing liver cancer liver cirrhosis patient least one biomarker monitoring early diagnosis liver cancer liver cirrhosis patient combination biomarkers selected group consisting bco cat cetp cfh bche afp fga serpina selenop uchl azgp serpina apoa apob crl cetp afp fgb serpind serpind serpina serpina lum qsox shbg serpina method one claim wherein control sample sample hepatitis b patient cirrhosis patient method one claim wherein step detecting quantifying biomarker performed elisa dip stick rapid analysis mass spectrometry microarray nucleic acid amplification immunoassay method claim wherein mass spectrometry mrm multiple reaction monitoring peptide mrm assay marker one listed table kit early diagnosis monitoring development liver cancer subject high risk developing liver cancer comprising agent detecting biomarker according one claim composition early diagnosis monitoring development liver cancer subject high risk developing liver cancer comprising agent detecting biomarker according one claim kit early diagnosis monitoring development liver cancer subject high risk developing liver cancer comprising agent detecting biomarker according one claim method according one claim method detecting vitro biomarker according one claim epa biomarker monitoring diagnosing onset liver | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 31 | cancer highrisk group liver cancer use thereof withdrawn epa en application claiming priority application number priority date filing date title kr pctkr woa en biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof publication publication number publication date epa true epa en epa epa en family id family application application number title priority date filing date epa withdrawn epa en biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof country status country link ep epa en kr krb en cn cna en wo woa en cited cited examiner cited third party publication number priority date publication date assignee title usb en bluefin biomedicine inc antiilrap antibody antibody drug conjugate family citing family cited examiner cited third party publication number priority date publication date assignee title cna en method detecting diseasecausing gene causing system disease cardiovascular symptom krb en genetic marker predicting risk hepatic fibrosis use thereof cnb en liver cirrhosis disease stage identification method based envelope line morphological feature analysis cnb en application cetp detection reagent preparation lung cancer screening kit cna en biomarker combination kit predicting recurrence risk liver cancer patient resection cna en application cat preparation hepatocellular carcinoma early diagnosis kit preparation screening antiliver cancer drug woa en method estimating fibrosis progression andor liver disease activity nonalcoholic steatohepatitis krb en biomarker diagnosis cancer use thereof cnb en application peripheral blood exosome mirna micro ribonucleic acid combined marker preparation hbv hepatitis b virus positive liver cirrhosis early liver cancer detection kit cnb en application nerve adhesion factor preparation reagent inhibiting marking liver cancer cell metastasis family cite family cited examiner cited third party publication number priority date publication date assignee title usa en affymetrix inc method apparatus detection fluorescently labeled material usa en affymetrix inc surfacebound unimolecular doublestranded dna usa en affymetrix inc printing molecular library array using deprotection agent solely vapor phase aua en affymetrix inc chipbased speciation phenotypic characterization microorganism usb en affymetrix inc gene expression evaluation system jpwoa en differentiation liver cancer determination disease stage prognosis prediction method kit krb en proteinic marker diagnosing hepatocellular carcinoma kra en apoa marker diagnosing hepatocellular carcinoma kit using marker kra en composition diagnosis hepatocellular cancer diagnosing kit comprising method screening anticancer agent cna en molecular marker early liver cancer application maker epa en leibniz institut fr analytische wissenschaften isas ev specific biomarkers hepatocellular carcinoma hcc woa en singapore health service pte ltd method diagnosing liver cancer subject kit diagnosing liver cancer krb en method screening cancer marker based deglycosylation glycoprotein marker hcc krb en biomarker diagnosis liver cancer use thereof usa en celgene corporation method treating solid tumor use biomarkers predictor clinical sensitivity immunomodulatory therapy kr kra patentkrben active ip right grant wo pctkr patentwoaen unknown cn cna patentcnaen active pending ep epa patentepaen notactive withdrawn cited cited examiner cited third party publication number priority date publication date assignee title usb en bluefin biomedicine inc antiilrap antibody antibody drug conjugate also published publication number publication date epa en kra en krb en woa en woa en cna en similar document publication publication date title epa en biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof krb en biomarker diagnosis liver cancer use thereof usb en apolipoprotein fingerprinting technique method related thereto epb en biomarker diagnosing liver cancer usb en metabolite biomarkers detection esophageal cancer using nmr krb en method diagnosis using lectin woa en method composition isolation identification plaque particle related biomarker lu et al detection identification serum peptide biomarker papillary thyroid cancer epb en cancer marker screening method detection deglycosylation glycoprotein hepatocellular cancer marker usa en composition diagnosis lung cancer diagnosis kit lung cancer usb en marker diagnostic method metastasis karczmarski et al preanalyticalrelated variability influencing serum peptide profile demonstrated mass spectrometrybased search colorectal prostate cancer biomarkers woa en biomarker diagnosis hepatoma use thereof usa en biomarker panel diagnosing pancreatic cancer use thereof chen et al targeted protein quantitation human body fluid mass spectrometry woa en apparatus method detection pancreatic cancer krb en protein biomarkers distinguishing malignancy | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
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"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 32 | intraductal papillary mucinous neoplasm use usb en method aiding diagnosis alzheimers disease evans et al prostate cancer proteomics urgent need clinically validated biomarkers cna en application molecular labeling eight kind protein identification placenta percreta invasive depth stomach cancer woa en mrmms signature assay krb en biomarkers predict tace treatment efficacy hepatocellular carcinoma karczmarski et al uncorrected paper press discovery novel potential protein diagnostic biomarkers prostate cancer serum tear usa en differential level haptoglodin isoforms small cell lung cancer legal event date code title description staa information status ep patent application granted ep patent free format text status international publication made puai public reference made article epc published international application entered european phase free format text original code staa information status ep patent application granted ep patent free format text status request examination made p request examination filed effective date ak designated contracting state kind code ref document designated state al bg ch cy cz de dk ee e fi fr gb gr hr hu ie li lt lu lv mc mk mt nl pl pt ro r se si sk sm tr ax request extension european patent extension state ba dav request validation european patent deleted dax request extension european patent deleted ric information provided ipc code assigned grant ipc gn afibhep supplementary search report drawn despatched effective date ric information provided ipc code assigned grant ipc gn afibhep staa information status ep patent application granted ep patent free format text status application deemed withdrawn application deemed withdrawn effective date | 1710.06481 | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | biomarker monitoring diagnosing onset liver cancer highrisk group liver cancer use thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 33 | cnb biomarker liver cancer diagnosis application thereof google patent cnb biomarker liver cancer diagnosis application thereof google patent biomarker liver cancer diagnosis application thereof download pdf info publication number cnb cnb cna cna cnb cn b cn b cn b cn cn cn cn b cn b cn b authority cn china prior art keywords protein liver cancer analysis peptide group prior art date legal status legal status assumption legal conclusion google performed legal analysis make representation accuracy status listed active application number cna language chinese zh version cna en inventor current assignee listed assignee may inaccurate google performed legal analysis make representation warranty accuracy list seoul national university industry foundation original assignee seoul national university industry foundation priority date priority date assumption legal conclusion google performed legal analysis make representation accuracy date listed filing date publication date priority claimed kr externalpriority application filed seoul national university industry foundation filed critical seoul national university industry foundation priority claimed pctkr externalpriority patentwoaen publication cna publication critical patentcnaen application granted granted critical publication cnb publication critical patentcnben status active legalstatus critical current anticipated expiration legalstatus critical link espacenet global dossier discus liver cancer disease title claim abstract description diagnosis method title claim abstract description biomarker substance title claim description detection method method claim abstract description blood anatomy claim abstract description blood substance claim abstract description mixture substance claim abstract description protein gene human gene claim description protein gene protein claim description analytical method method claim description liver cirrhosis disease claim description chemical reaction reagent substance claim description antibody human gene claim description antibody protein claim description fn human gene claim description fibronectins protein claim description fibronectin effect claim description f human gene claim description prothrombin protein claim description prothrombin drug claim description elisa method claim description complement effect claim description binding effect claim description immunoelectrophoresis method claim description tissue anatomy claim description aptamer polymer claim description itih protein claim description itih human gene claim description igfals human gene claim description igfals protein claim description immunoblotting method claim description microarray method claim description protein immunostaining method claim description immunodiffusion effect claim description immunoprecipitation method claim description ligand substance claim description preparation method method claim description radioimmunoassay method claim description fluorescenceactivated cell sorting method claim marker substance abstract description sensitivity effect abstract description prognosis method abstract description development method abstract description developmental process effect abstract description assay kit method abstract therapeutic procedure method abstract sample substance description hepatocellular carcinoma disease description hepatocellular carcinoma toxicity description processed protein peptide human gene description processed protein peptide protein description multiple reaction monitoring method description hepatic cirrhosis disease description alphafetoproteins protein description alphafetoproteins human gene description serum anatomy description bdagihxwwsansruhfffaoysan formic acid chemical compound oco bdagihxwwsansruhfffaoysan description nucleic acid chemical class description nucleic acid protein description ion chemical class description sodiuminfluxstimulating peptide protein description substance substance description recovery method description auc effect description phosphotransferases human gene description phosphotransferases protein description bioassay method description method method description alb human gene description alb protein description albumin drug description hepatitis disease description polylactic acidcoglycolic acid polymer description corresponding effect description disease disease description hepatitis toxicity description amyotrophic lateral sclerosis disease description cndp human gene description immunoassay method description mass spectrometry method description reverse transcription pcr method description itih protein description binding method description biological sample substance description cancer disease description exhibiting effect description formic acid nutrition description substrate substance description cndp protein description fibrin drug description fibrin protein description fibrin human gene description homo sapiens specie description liver anatomy description plasminogen protein description plasminogen human gene description cell anatomy description liver disease disease description ozaifhulbgxakxuhfffaoysan precursor substance nccccnnccccn ozaifhulbgxakxuhfffaoysan description cholinesterase human gene description cholinesterase protein description hgf activator protein description | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 34 | hgfac human gene description nucleic protein protein description cholinesterase drug description detectable effect description hybridization method description immunoblot method description labelling method description manufacturing process method description measurement method description quantitative analysis method description vitamin binding protein human gene description vitamin binding protein protein description ambp protein description ambp human gene description igfbp human gene description kdxkernsbixsrkyfkpbyrvsan llysine chemical compound nccccchncoo kdxkernsbixsrkyfkpbyrvsan description ffearjckvfrzrrbypyzucnsan lmethionine chemical compound csccchncoo ffearjckvfrzrrbypyzucnsan description plasma anatomy description proteome protein description vtn human gene description vitronectin protein description alphaantiplasmin protein description alphaantiplasmin human gene description amino acid chemical class description binding agent substance description blood level effect description distribution method description glass substance description insitu storage method description logistic regression method description qualitative analysis method description tumor marker substance description xsqukjjjfzcrtkuhfffaoysan urea chemical compound ncno xsqukjjjfzcrtkuhfffaoysan description protein description human gene description arginine substance description clusterin protein description clusterin human gene description enzyme drug description enzyme human gene description enzyme protein description factor xi protein description fibrosis disease description igfbp protein description itih protein description itih human gene description insulinlike growth factor binding protein human gene description insulinlike growth factor binding protein protein description interferon human gene description interferon protein description lysine substance description nitrocellulose substance description plgla human gene description plgla protein description pzp protein description acid substance description chemical reaction method description chromatography analysis method description effect effect description fibrosis effect description interferon drug description nitrocellulos polymer description normalization method description product substance description protein marker substance description proteomic method description trypsin substance description vhjlvaabsrfdpmuhfffaoysan dimercaptobutanediol chemical compound sccococs vhjlvaabsrfdpmuhfffaoysan description ahsg protein description ascites disease description afynaddzulbejauhfffaoysan bicinchoninic acid chemical compound cccccnccccccccccncoocccooc afynaddzulbejauhfffaoysan description blood level effect description ec protein description glypican human gene description glypican protein description homo specie description islr human gene description islr protein description immunoglobulin human gene description immunoglobulin protein description inflammation disease description pgltvomixtuurauhfffaoysan iodoacetamide chemical compound ncoci pgltvomixtuurauhfffaoysan description onibwkktopoviabypyzucnsan lproline chemical compound ocochcccn onibwkktopoviabypyzucnsan description lcat human gene description lcat protein description nuc protein description ybyrmvivwmbxkquhfffaoysan pmsf chemical compound fsooccccccc ybyrmvivwmbxkquhfffaoysan description polystyrene substance description ribonuclease human gene description ribonuclease protein description serum concentration effect description trypsin protein description trypsin human gene description alphamicroglobulin protein description alphamicroglobulin human gene description alphalfucosidase human gene description alphalfucosidase protein description antigen substance description antigen protein description antigen human gene description bead substance description carbamide substance description centrifugation method description collagen polymer description data analysis method description decreasing effect description derivation method description diagnostic procedure method description shibstmrcdjxlnkczcntnesan digoxigenin chemical compound cchccccochchccccchocchcccchocccooc shibstmrcdjxlnkczcntnesan description elution method description equilibration method description hepatic effect description inflammatory process effect description injection method description injection substance description noesyzhrgyrdhsuhfffaoysan insulin chemical compound ncocncoccccnoncoccccooncoccccncocncocncccccsscccnccoconcccccconccccccoccconccccnoconcccccconccccooconcccnoconccccccoccconccssccncoccccncocccccncoccccccoccncocccccncoccncoccccooncoccccncocccccncocccncncncocconcocncoconcconccccooconccccncnnconcconccccccccconccccccccconccccccoccconcccoconccccconcccccnconcccooconcccnocoooncocccccncocconcoccconcoccssccncocccccncocncoccccnoncocccnoncocncocncccccccccccccncn noesyzhrgyrdhsuhfffaoysan description inteinmediated protein splicing effect description lipid chemical class description magnetic resonance imaging method description matrix material substance description microparticle substance description nanoparticle substance description nuca protein description nucleic acid amplification method method description peptidomimetic substance description polymerase chain reaction method description polystyrene polymer description protein supplement nutrition description radioactive substance substance description research method description serological effect description vypsynlajgmnejuhfffaoysan silicium dioxide chemical compound osio vypsynlajgmnejuhfffaoysan description solution substance description statistical method method description supernatant substance description surgical procedure method description tandem mass spectrometry method description trypsin drug description trypsin inhibitor substance description ultrasonography method description ribonucleotidesnm polymer description lenzdbcjohfcasuhfffaoysan aminohydroxymethylpropanediol chemical compound occncoco lenzdbcjohfcasuhfffaoysan description actb human gene description actb protein description acti protein description ahsg human gene description apc human gene description | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 35 | apc protein description abdominal pain disease description alcohol abuse disease description alkaline phosphatase human gene description alkaline phosphatase protein description blood concentration effect description body fluid anatomy description c human gene description ccnd human gene description ccnd protein description ctsb protein description capillary anatomy description capra specie description carboxypeptidase b human gene description carboxypeptidase b protein description cathepsin b human gene description cathepsin b protein description chronic hepatitis disease description collagen protein description collagen human gene description coma hepatic disease description complement c protein description complementary dna polymer description connective tissue anatomy description cystic fibrosis transmembrane conductance regulator human gene description cystic fibrosis transmembrane conductance regulator protein description dna amplification effect description dna microarray method description dpom protein description diagnostic kit method description ec human gene description ec protein description ec protein description ec protein description ervk human gene description escherichia coli specie description gcat protein description glb human gene description glb protein description hp human gene description hsp heatshock protein human gene description hsp heatshock protein protein description haemorrhage disease description haemorrhagic disease disease description haptoglobin protein description heparin drug description zfgmdibridkwmypastxaensan heparin chemical compound cconchchochochcosoooochochchcooochochchchosooochochchocochosooochocooochocsooochocho zfgmdibridkwmypastxaensan description hepatic rupture disease description hepatitis viral disease description hepatocytes anatomy description horseradish peroxidase protein description hspaa protein description igf human gene description igf protein description immunoglobulin protein description immunoglobulin g protein description injury disease description insulin human gene description insulin protein description insulinlike growth factor binding protein protein description insulinlike growth factor ii human gene description insulinlike growth factor ii protein description iti specie description jaundice disease description klk human gene description klkb human gene description klkb protein description hndvdqjcigzpnoyfkpbyrvsan lhistidine chemical compound ocochncccncn hndvdqjcigzpnoyfkpbyrvsan description mdv protein description mammalia specie description muscle weakness disease description muscular weakness disease description nodule disease description nucleic acid sequence polymer description nylon substance description oryctolagus cuniculus specie description polb protein description peptidase human gene description peptidase protein description persistent generalised lymphadenopathy disease description plasma kallikrein human gene description plasma kallikrein protein description plasminogen activator protein description plasminogen activator human gene description portal system anatomy description rassf human gene description rassf protein description rf protein description receptor kinase protein description serpina human gene description snap human gene description snap protein description spint protein description spint human gene description srda human gene description srda protein description tacp protein description thrb protein description tyrp protein description tyrp human gene description transferrin human gene description transferrin protein description gsejcltvzplzkyuhfffaoysan tris chemical compound occnccocco gsejcltvzplzkyuhfffaoysan description tris buffer substance description urine anatomy description virus specie description vitamin k deficiency disease description absorbance method description acarboxyprothrombin protein description activation effect description activator substance description alcohol use disease disease description alpha antitrypsin protein description alpha antitrypsin human gene description alpha antitrypsin drug description alphahsglycoprotein protein description alphahsglycoprotein human gene description amplification effect description antigenic effect description assay method method description betagalactosidase protein description binding buffer substance description biosynthetic process effect description ybjhbahktgyvgtzkwxmuahsan biotin chemical compound nconchchcccccooscch ybjhbahktgyvgtzkwxmuahsan description biotin drug description biotin nutrition description biotin substance description bleeding effect description bleeding toxicity description blood sampling method description blood test method description body fluid substance description uiimbognxhqvgwuhfffaoysam buffer substance naocoo uiimbognxhqvgwuhfffaoysam description calculation algorithm method description capillar electrophoresis method description cata protein description cellulose polymer description cellulose substance description chronic effect description collagen drug description competitive effect description complementary dna substance description computed tomography method description confocal microscopy method description conjugation effect description construction method | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 36 | description conventional method method description correlated effect description data mining method description death effect description desalination reaction method description desalting method description diagnostic biomarker substance description drug substance description drug drug description electrophoresis method description engineering process method description lfqscwfljhtthzuhfffaoysan ethanol chemical compound cco lfqscwfljhtthzuhfffaoysan description evaluation method description experimental method method description filtration method description firing method description fluorescent dye substance description formation reaction method description fragmentation reaction method description freezing method description fusion effect description gel substance description genetic effect description glycans polymer description pchjsuwpfvwcpouhfffaoysan gold chemical compound au pchjsuwpfvwcpouhfffaoysan description gold substance description gold inorganic material description gravity effect description hbaa protein description heparin polymer description heparin receptor protein description hepatic coma disease description human plasminogenrelated protein human gene description human plasminogenrelated protein protein description hydroxy group chemical group ho description hypertrophic effect description immunogen effect description impregnation method description vitro method description infiltration method description inhibitor substance description inhibitory effect effect description ion trap method description ion trap mass spectrometry method description kallistatin protein description leucinerich repeat protein protein description liquid chromatographytandem mass spectrometry method description liquid phase substance description liver function effect description load method description lysine group chemical group hnhchhchhchhchhchnhhco description machine learning method description magnetic particle substance description malignancy effect description melting method description membrane substance description metabolic effect description metastatic cancer disease description microarray analysis method description mixing method description multivariate analysis method description necrotic cell death effect description novel biomarker substance description nucleic acid array method description nylon polymer description particle substance description phase substance description plastic substance description plastic polymer description polyacrylamide gel electrophoresis method description polypeptide polymer description polysaccharide polymer description polysaccharide substance description polysaccharide polymer description pooling method description processing method method description protease nutrition description protein array method description protein assay method description protein binding assay method description random forest analysis method description receptor protein description receptor human gene description regeneration effect description regeneration method method description responsiveness effect description reverse transcription method description rna polymer polymer description scar toxicity description separation method method description silicon dioxide substance description sodium dodecyl sulfate polyacrylamide gel electrophoresis method description solid phase substance description survival effect description suspension substance description test method method description thermotherapy method description tomography method description transcription effect description transferrin substance description type analysis method description vascular effect description viral hepatitis disease description vitamin k deficiency bleeding disease description water type substance description western blot method description image classification gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnspecifically defined cancer gnspecifically defined cancer liver pancreas kidney gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnproduction immunochemical test material gnproduction labelled immunochemicals gnproduction labelled immunochemicals fluorescent label gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer abstract present invention discloses marker combination marker used diagnosis prognosis therapy monitoring liver cancer high accuracy sensitivity marker present invention used simple effective diagnosis monitoring liver cancer noninvasive examination using blood developed various test kit | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 37 | used effectively early detection liver cancer home general hospital example poct development description biomarker liver cancer diagnosis application thereof technical field invention relates biomarker liver cancer diagnosis application thereof background liver cancer hepatocellular carcinoma hcc common type adult liver cancer occupying third place among cause death due cancer stefaniuk p et al world jgastroentol stefaniuk p et al world gastroenterology journal liver cancer disease symptom developed certain extent thus often case proper treatment period missed prognosis poor even treatment performed particular impossible remove liver cancer surgery liver cancer critical disease dy within one year considering clinical situation technology enables early diagnosis prognosis prediction cancer realistic measure cancer treatment guideline treatment liver cancer next generation particular known hepatocellular carcinoma disease likely occur patient risk factor hepatitis virus alcohol cirrhosis clear screening surveillance surveillance test highrisk group need performed using early diagnosis marker indeed investigation shown early diagnosis six month interval increase survival rate liver cancer patient reduces mortality biomarker test capable accurately finding liver cancer normal human early stage developed test method used noninvasive early diagnosis liver cancer highrisk population serum alphafetoprotein test although reference value afp alpha fetoprotein proposed time development able achieve good level sensitivity specificity ngml case sensitivity exceed liver cancer diagnosis performed basis ngml according liver cancer diagnosis guideline current international academic conference sensitivity although specificity increased according result present study afp known sensitivity specificity whole thus liver cancer patient diagnosed addition although determined diagnostic standard serum marker useful diagnosis liver cancer include decarboxylated prothrombin dcp prothrombinii induced vitamin k deficiency pivkaii distribution glycosylated afp relative total afp lfraction l ratio alphafucosidase alpha fucosidase glypican glypican heat shock protein hsp like however individual serum marker significant prognostic factor used screening test low accuracy used alone considered method early diagnosis liver cancer using single serological marker reached limit addition practice patient diagnosed stage radical treatment surgery highfrequency thermotherapy possible limited total liver cancer patient u patent publication relates method composition diagnosing liver cancer discloses method diagnosing liver cancer detecting cpg island basf spint apc ccnd cftr rassf srda gene korean patent relates novel biomarker liver cancer use thereof discloses marker diagnosis liver cancer prognosis analysis liver cancer detecting nk protein like therefore urgent need develop following marker ie marker make maximum early diagnosis stage radical treatment liver cancer performed improved specificity sensitivity able overcome limitation individual examination disclosure invention technical problem present invention provides biomarker capable diagnosing liver cancer technical scheme one embodiment present invention provides composition diagnosis prognosis liver cancer comprising detection reagent biomarker selected group consisting al insulinlike growth factorbinding protein complex acid labile subunit ambp alphamicroglobulinbikunin precusor alphamicroglobulinbikunitz inhibitor precursor cpb carbopypeptidase b carboxypeptidase b chle cholinesterase clus clusterin dpbetaalahis dipeptase carnosine dipeptidase co complementary component c complement component n cpn fibrin linker fibrin linker n peptidase nc fibrin linker nc fibrin linker nc fibrin linker nc fibrin linker hgfa hepatocyte growth factor activator ibpinsulinlike growth factorbinding protein igfinsulinlike growth factor ii itihinteralphatrypsin inhibitor heavy chain h kain kallistatin tissue kallikrein klkbplasma kallikrein lcat phosphatidylcholinesterol acyltransferase plga plasminogenrelated protein plmn plasminogen thrb prothrombin vtdb vitamin binding protein vtnc vitronectin another aspect present invention provides method detecting liver cancer marker vitro method comprising step presence andor concentration nucleic acid andor protein biological sample derived subject detected biomarker selected group consisting al insulinlike growth factorbinding protein complex acid lipid supplement ambp alphamicrobubulinbikunin precursor cpb carbopypeptidase b chle cholesterase clus clus clus cndpbetaalahis dipeptidase co complex component c cpn carbopxypeptidase n supplement fa coogine factor xi fiholin fibrosis hgp receptor heparin receptor kinase ih igf kinase ii interferon kinase ii interferon kinase ii insulininterferon kinase albumin kinase ii insulin kinase ii albumin kinase iii insulinalbumin kinase albumin kinase iii albumin insulinkinase ii albumin kinase iii insulinalbumin kinase iii albumin igf kinase ii albumin interferon kinase ii albumin iprotein kinase ii albumin igf albumin ii alphai alphai plga plasminogenrelated protein plmn plasminogen thrb prothrombin vtdb vitamin binding protein vtnc vironectin comparing result detection level presence | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 38 | said nucleic acid said protein corresponding result said biomarker control sample determining target body sample liver cancer concentration nucleic acid protein target body sample changed presence absence nucleic acid protein changed comparing sample control group sample marker present invention detected using serum sample differentially expressed liver cancer patient comparison sample derived normal person hepatitis patient cirrhosis patient patient healed treatment liver cancer thus effectively used diagnosis liver cancer patient early diagnosis patient progressed cirrhosis liver cancer measurement progression treatment advantageous effect biomarker invention diagnose liver cancer higher specificity sensitivity particular since biomarker present invention distinguish liver cancer patient also liver cirrhosis liver cancer patient possible perform early diagnosis advance patient progress liver cirrhosis liver cancer since possible distinguish liver cirrhosis patient state liver cancer removed liver cancer healed possible use biomarker present invention predicting prognosis liver cancer treatment addition marker present invention used noninvasive diagnosis using blood thus useful early detection home general hospital used detection liver cancer simple blood test health test thus effect reducing medical cost national point view biomarker present invention developed form diagnostic kit using antibody protein peptide biomarker example form elisa enzyme linked immunosorbent assay rapid kit form strip peptidebased mrm mass spectrometry multiple reaction monitoring kit particular method detecting peptide mrm applied method improving exceeding conventional liver cancer diagnosis method case performing industrialization replacing conventional immunoassay method clinical application hospital performing analysis setting weight value using afp known liver cancer marker drawing fig illustrates mrm analysis process used discovery analysis biomarkers fig show whether endogenous synthetic peptide eluted simultaneously elution fig show q intensity pattern endogenous synthetic peptide blood fig show method confirming level endogenous peptide blood fig graph showing result measurement concentration endogenous peptide blood dynamic range dynamic range distribution fig show blood level low high abundance low high abundance target fig schematically show manner determining concentration si peptide injection fig show result establishing multiple protein labeling panel lc panel hcc panel fig show result establishing multiple protein marker panel hcc group recovery group fig show result immunoblotting test ten target protein whose expression tendency consistent order examine early diagnostic marker fig show aap alphaantiplasmin antiplasmin protein fig b show ambp protein fig c show afp alphafetoprotein protein fig show catb cathepsin b protein fig e show fetua alphahsglucoprotein hsglycoprotein protein fig f show finc fibronectin fig g show itih interimtrypsin h protein inter trypsin inhibitor heavy chain h fig h show itihinteralphatrypsin inhibitor heavy chain h inter trypsin inhibitor heavy chain h protein fig show plga plasminogenrelated protein protein fig j show thrb prothrombin protein fig show result protein level detection method using group lc hcc recovery detection reagent elisa analysis detailed description present invention based finding proteinspeptides exhibit significant difference among group effective biomarkers liver cancer diagnosis sequentially screening testing expression amount differentially expressed proteinspeptides using sample treatment patient liver cirrhosis liver cancer subject using mrm technique thus one aspect present invention relates composition kit diagnosing assessing liver cancer advance comprises peptide protein selected group consisting igfals insulinlike growth factorbinding protein complex acid lipid supplement ambp alphamicrolobulinbikunin predictor cpb carbopxyphopsizing b chle cholinester clus clusterin cndpbetaalahis dipeptidase co complementary component c cpn carbophopplerotidase n fa coaggation factor xi fibrosidase fibronectin hgkehepatotoxin collagen factor plga plgacollagen protein supplement plga protein supplement plg reagent detecting one biomarkers selected group consisting plmn plasmodigen thrb prothrombin vtdb vitamin binding protein vtnc vitronectin present invention liver cancer hepatocellular carcinoma hcc refers primary malignancy occurring liver tissue occurs patient risk factor alcohol abuse viral hepatitis metabolic liver disease case liver cancer bleeding cellular necrosis occur due absence fibrous matrix causing vascular infiltration hepatic portal system severe case lead liver rupture intraabdominal blood leakage liver cancer distinguished cirrhosis cirrhosis finally present symptom hepatocyte injury scar liver function attenuation ascites hemorrhagic disease hepatic coma due regeneration nodule fibrosis liver tissue resulting chronic inflammation occurring liver | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 39 | case liver cancer patient hepatitis inflammation liver cirrhosis fibrosis common hepatitis eliminated drug liver cancer patient liver cirrhosis patient diagnosed liver cancer thus important distinguish liver cirrhosis liver cancer present invention term diagnosis includes determining susceptibility susceptivity subject disease disease determining whether particular disease condition currently present determining trend metastatic cancer state stage progression cancer determining responsiveness cancer treatment subject particular disease disorder performing thermometrics eg monitoring guest status purpose providing information treatment efficacy present invention prognostic evaluation includes determining whether recover diagnosed liver cancer receiving treatment present invention term diagnostic biomarker diagnostic marker diagnostic marker substance capable distinguishing patient develops liver cancer patient cirrhosis patient normal cell patient receives appropriate liver cancer treatment diagnosis includes protein exhibit concentration change sample particularly blood derived patient liver cancer compared sample control group polypeptide derived protein gene encoding protein fragment thereof amount biomarker present invention increased blood liver cancer patient compared control group sample sequence biomarker present invention searched uniprot database wwwuniprotorg example using id described table marker invention use combination one marker eg two three four five marker used existing marker eg afp andor diagnostic method eg hepatic ultrasound etc combination marker satisfying desired sensitivity specificity screened person skilled art method described present example ie method analysis using biological sample subject including normal person patient andor logistic regression logistic regression analysis one embodiment present invention one marker al cbpb clus cndp cpn fa finc hgfa used marker differentially expressed control group liver cancer patient higher auc area curve value primary secondary sample group described example present invention another embodiment invention finc marker used alone combination thrb finc combination al itih thrb finc another embodiment invention biomarker determining whether recovery treatment liver cancer selected group consisting thrb finc itih ibp plmn cbpb plga said marker combination marker particularly high auc value excluding marker combination another embodiment one marker present invention used combination afp marker marker invention detected quantitative qualitative analysis based detection presence absence nucleic acid particular protein andor mrna messenger ribonucleic acid andor expression level change expression level level difference expression level present invention detection mean detection including quantitative andor qualitative analysis includes detection presence absence expression amount method known art skilled art select appropriate method carrying present invention detection marker present invention may based functional andor antigenic characteristic marker one embodiment marker invention detected detecting activity function marker using specifically interacting substance based level nucleic acid encoding protein particular mrna andor protein another embodiment detection marker present invention performed detecting corresponding peptide derived marker protein example peptide corresponding marker described table one protein one two peptide may used aspect detection reagent contained composition present invention reagent capable detecting marker present invention quantitative qualitative analysis various way based protein nucleic acid level quantitative qualitative analysis marker present invention various method known qualitative quantitative detection protein nucleic acid used qualitative quantitative detection method based protein level method immunoblot assay elisa radioimmunoassay immunodiffusion immunoelectrophoresis tissue immunostaining immunoprecipitation analysis complement fixation analysis method using binding labeled antibody solutionsuspension mass analyzer protein array using antibody like used alternatively qualitative quantitative detection method based nucleic acid level nucleic acid transcription amplification method method using etag system system based labeled magnetic bead array system nucleic acid array like used method known method example reference made chipbased chromatography electrophoresis color et al j chromatography chip capillary electrophoresis colier et al j chromatography mass spectrometry petricoin et al lancet mass spectrometry petricoin et al lancet etag system chanhuiet al clinical immunology etag system chanhui et al clinical immunology microparticleenhanced nephelometric immunoassay | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 40 | montagne et al eur j clin chem clin biochem microparticle enhanced immunoturbidimetry assay monta et al j european j clin biochem like one embodiment present invention label detected mass spectrometry mass spectrometry performed example manner described example separating protein peptide sample referred example kim et al j proteome re gold et al j proteomics anderson l et al mol cell proteomics anderson l et al molecular cell proteomics one embodiment example mass spectrometry multiple reaction monitoring mrm technique using example triple quadrupole liquid phase secondary mass spectrometry lcmsms qtrap linear ion trap mass spectrometry like used mrm method capable quantitatively accurately performing multiplex measurement substance trace amount biomarkers present living body sample selectively transferring precursor ion parent ion among ion fragment generated ion reduction process collision tube using first mass filter q precursor ion arriving collision tube collide internal collision gas fragmented generate product ion ion ion transferred second mass filter q specific ion transferred detection unit transfer mrm method analysis method high selectivity sensitivity detect desired component information manner example reference may made gillette et al nature method gillette et al nature method another embodiment binding agent specifically bind protein mrna derived gene encoding protein array comprising binding agent used yet another embodiment sandwich immunoassay elisa enzyme linked immunosorbent assay ria radio immune assay like may used method detect protein qualitatively quantitatively binding antibody radioactive substance eg polystyrene adding biological sample first antibody bound magnetic bead membrane slide microplate made solid phase matrix glass plastic eg polystyrene polysaccharide nylon nitrocelluloseh ori fluorescent substance chemiluminescent substance hapten biotin digoxigenin digoxigenin like labeled directly indirectly detectable labeling substance conjugated enzyme horseradish peroxidase alkaline phosphatase malate dehydrogenase like develops color emits light action substrate another embodiment ouchterlony plate easily detect label antigenantibody binding western blotting immunoelectrophoresis immuno electrophoresis crossed ie cross immunoelectrophoresis rockettie rocket immunoelectrophoresis fused rockettie fusion rocket immunoelectrophoresis affinity ie affinity immunoelectrophoresis used enzyme immunoassay et maggio ed crcpress boca raton florida enzyme immunoassay et maggio man crc press bocardon florida abovementioned immunoassay immunostaining method described gaastra ww enzymelinked immunosorbent assay elisa method molecular biology vol walker jmed humana press njgaastra enzymelinked immunosorbent assay elisa molecular biology method vol walker jm men humana press new jersey etc occurrence disease diagnosed analyzing final signal intensity resulting abovedescribed immunoassay process ie performing signal control normal sample reagent substance used method known reagent substance example antibody substrate nucleic acid peptide aptamer specifically bind abovementioned marker receptor ligand cofactor specifically interacts abovementioned marker used reagent substance specifically interacting binding abovementioned label present invention may used together chip format nanoparticle nanoparticle addition marker invention detected quantitatively andor qualitatively using variety wellknown method based nucleic acid level particularly mrna level qualitative quantitative detection method based nucleic acid level example detection based mrna level detection expression amount pattern method using reverse transcriptionpolymerase chain reaction rtpcrpolymerase chain reaction competitive rtpcr realtime rtpcr nuclease nuclease protection assay npa eg ribonuclease rnase snuclease cycle assay situ situ hybridization method dna microarray chip nuter hybridization etc wellknown assay method may used may performed using commercially available kit skilled art make appropriate selection carrying present invention example knose hybridization advantage size transcript existing cell known various probe used npa useful multiplex marker analysis situ situ hybridization method easily recognizes position transcript mrna cell tissue reverse transcription polymerase chain reaction useful detection small amount sample addition binding agent specifically bind nucleic acid mrna crna complementary nucleic acid gene encoding biomarker protein present invention array comprising binding agent may used reagent substance used biomarker detection method based abovementioned nucleic acid level wellknown reagent substance example method determining presence absence mrna amount mrna reverse transcription rtpcr detection reagent include example polymerase probe andor primer pair specific mrna marker present invention primer probe refers nucleic acid sequence capable binding complementarily template free | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 41 | hydroxyl group oh enables reverse transcriptase dna polymerase begin template replication detection reagent used present invention may labeled coloremitting lightemitting fluorescent substance described detect signal one embodiment detection mrna use made knose hybridization reverse transcription pcr polymerase chain reaction latter case reverse transcription pcr method rna particularly mrna sample isolated cdna synthesized therefrom specific gene sample detected using specific primer combination primer probe whereby presenceabsence expression level specific gene determined method described example han het alcancer re korea h et al advance cancer research detection reagent included composition present invention may labeled detection either directly indirectly sandwich format depending method used detection case direct labeling method serum sample used array like labeled fluorescent label cy cy case sandwich method unlabeled serum sample first reacted array detection reagent attached bound target protein bound labeled detection antibody carry detection since sensitivity specificity improved case sandwich method detection performed even pgml level addition radioactive substance colordeveloping substance magnetic particle highdensity electronic particle like used labeling substance fluorescence obtained using confocal microscopy example affymetrix inc agilent technology inc etc composition invention may comprise one additional component required binding assay example binding buffer reagent required preparing sample blood sampling syrinx negative andor positive control composition present invention comprising plurality detection reagent described provided composition elisa analysis rapid test strip kit dip kit analysis mrm analysis microarray gene amplification immunoassay according analysis method appropriate detection reagent screened according analysis method one embodiment kit rapidly detected using elisa test paper case antibody present invention recognizing one marker may attached surface well glass plate multiwell plate substrate nitrocellulose example case test strip following technique widely used field poct point care test one antibody recognizing biomarker according present invention bound substrate nitrocellulose brought contact sample serum example one end test strip immersed serum sample sample move substrate due capillary phenomenon thereby detecting marker chromophoric manner sample bound antibody substrate another embodiment peptidebased mrm kit provided manner described mrm mrm method method using peptide selectively recognizing specific protein detect marker biological sample stably conventional method using antibody sensitive environment temperature humidity example peptide described table present invention may used peptide one two peptide may used one marker example peptide corresponding protein represented letter amino acid therein prothrombin thrb hqdfnsavqlvenfcr sgiecqlwr fibronectin finc wcgttqnydadqkgewtciaysqlr htsvqttssgsgpftdvr itihevafdleipk ldaqasflpk ibp alaqcapppavcaelvr plmnlsspavitdk eaqlpvienk cbpbdtgtygfllper yplyvlk plgadvvlfek another embodiment kit may provided form array chip comprising microarray detection reagent may attached surface substrate glass digested cellulose array fabrication technique reference may made schena et al proc natl acad sci proc natlacadusa usa schena et al science u pat no detection reagent attached array include example antibody antibody fragment aptamers aptamers affinity multimers avidity multimers peptidomimetics peptidomimetics capable specifically binding protein another aspect present invention relates kit system diagnosis liver cancer prognosis analysis liver cancer comprising detection reagent biomarker detection reagent method using reagent described view fact reagent capable detecting marker present invention present dispensed divided container present invention also relates deviceapparatus dividing containing marker detection reagent present invention addition kit may comprise instruction use still another aspect present invention relates method detecting liver cancer marker comprises step detecting presence absence protein selected group consisting al insulinlike growth factorbinding protein complex acid labilesulbut ambp alphamicrolobulinbikunin precusor cpb carbopypeptidasb chle cholinester clus clusterin cndpbetaalahis dipetidase co complementary component c cpn carbopxypeptidast n subutyrate fa conjugation factor xi finc connective tissue hgfa heparin protein protein kplga plgaplga plga plgaprotein proteinprotein plgaprotein proteinpromoter plgaprotein protein plgapromoter plgaprotein protein plgaprotein proteinpromoter plgaprotein protein complex plgaprotein protein plgaproteinpromoter plgaprotein protein plgaprotein protein proteinpromoter plgaprotein proteinpromoter plga plgaprotein protein proteinpromoter protein promoter protein protein proteinpromoter protein quality andor concentration detection method | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 42 | detecting liver cancer marker present invention comprises step comparing result detection level presence said nucleic acid said protein result corresponding said marker control sample determining target body sample liver cancer concentration nucleic acid protein target body sample changed presence absence nucleic acid protein changed comparing sample control group sample method present invention sample used control group diagnosis liver cancer patient may sample derived normal person hepatitis patient cirrhosis patient patient heals treatment liver cancer maintenance cirrhosis expression level marker present invention increased liver cancer patient compared control patient biological sample used method present invention whole blood serum plasma expression level marker present invention increased liver cancer patient compared sample derived normal person liver cirrhosis patient therefore since liver cancer diagnosis distinguish patient liver cirrhosis liver cancer method present invention possible diagnose patient progress liver cirrhosis liver cancer particularly advantageous early diagnosis case control group may include sample derived patient liver cirrhosis sample derived patient liver cirrhosis includes patient liver cancer recovery maintains liver cirrhosis addition method present invention also useful discriminating patient recovered liver cancer treatment case liver cancer sample derived patient used control group present invention biological sample refers substance mixture substance containing one component capable detecting biomarker biological sample includes living body particularly body fluid especially including limited whole blood plasma serum urine one embodiment present invention one marker al cbpb clus cndp cpn fa finc hgfa particularly suitable marker expressed differently control group liver cancer patient higher auc primary secondary sample group described example present invention another embodiment present invention biomarker determining whether recovery treatment selected group consisting thrb finc itih ibp plmn cbpb plga another embodiment present invention finc marker may used alone combination thrb finc combination al itih thrb finc may used another embodiment one marker present invention used combination afp marker control group reference group used method method detecting biomarker reagent used method method analyzing data judgment referred content described content described method present invention carried using aforementioned method method using detection reagent particularly method present invention carried protein nucleic acid microarray analysis method nucleic acid amplification method antigenantibody method mass spectrometry method subject method present invention includes mammal particularly human human subject includes person suspected hcc hepatitis cirrhosis patient person need hcc diagnosis person suspected one embodiment method performed subject symptom associated liver disease abdominal pain hypertrophic liver ascites jaundice muscle weakness hepatitis eg hcv hepatitis esophageal phlebangioma like used determine whether subject symptom hcc embodiment human subject one normal appearance exhibit symptom hcc embodiment subject may also person diagnosed hcc based afp since plasma afp concentration subject may low normal case serum concentration afp may mugl nondetectable mugl example mugl nondetectable mugl mugl mugl mugl mugl mugl mugl case combination comprising two marker used using method described data set may generated includes expression profile profile ie quantitative information associated marker protein expression sample expression profile obtained using marker whether sample subject hepatocellular carcinoma determined comparing result reference group control group control group reference group may normal sample negative control group sample derived patient treated suffering hepatocellular carcinoma sample derived patient positive control group judged hepatocellular carcinoma method marker present invention sample derived cirrhosis patient sample derived hepatitis patient one embodiment present invention sample derived normal human sample derived patient determined treated hepatocellular carcinoma used | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 43 | control group reference group used comparison obtained expression profile comparison expression profile marker control group test group using sample known method used example reference may made digital image comparison expression profile comparison using db expression data comparison described u pat no expression profile obtained detection marker present invention processed using known data analysis method example data analysis method may use nearest neighbor classifier nearest neighbor classifier partialleast square partialleast square svm support vector machine adaboost iterative algorithm clusteringbased classification clusteringbased classification method described bioinformatics wang et al bioinformatics bmc bioinformatics liu et al genome ser workshop genome info yeang et al bioinformatics application xiague et al xiaguetechnologies biotechnology quest et al bmc bioinformatics addition order determine result detected marker present invention useful discrimination hepatocellular carcinoma various statistical processing method used one embodiment logistic regression logistic method used statistical processing method referred ruczinski journal computational graphical statistic method similar cart method classifier provided binary tree node us operator generated cart relatively general boolean operator associated characteristic example analytical method include recently narrowed center gravity nearest shrunken centre tibshiranipnas proc natl acad sci usa random forest random tree breimanmachine learning mart hastine element statistical learning springer one embodiment order diagnose hcc statistical treatment degree reliability regarding significant difference test substance control group determined metadata used statistical treatment value double triple multiplex analysis performed marker statistical analysis method useful making clinically significant judgment statistical processing biomarkers clinical genetic data method present invention may used determining severity hcc example hcc judged mild hcc moderate hcc severe hcc comparing expression profile positive control group negative control group furthermore result expression profile classified according predetermined criterion performing analysis expression profile marker predetermined hcc population expensive examination magnetic resonance imaging mri also made way early detection another embodiment method may performed several time particular period year may used monitoring evolution change expression pattern depending type marker increase decrease expression may correlated status hcc method used determine onset impregnation deterioration etc hcc comparison value previous examination subject value control group precaution may taken prevent progression hepatocellular carcinoma severe hepatocellular carcinoma based change hcc marker time definitive diagnosis hcc biomarkers used auxiliary unit used together diagnostic method afp examination ultrasonography computed axial tomography ct scan examination magnetic resonance imaging mri examination hereinafter example provided facilitate understanding present invention however following example provided easier understanding present invention present invention limited following example example example clinical sample information use present invention trial performed according protocol allowed ethical review board medical research seoul university written consent based full instruction obtained patient clinical information shown order select marker candidate group select protein candidate group exhibiting expression difference pooled pooling sample normal person liver cancer patient study performed using sample normal person malefemale sample liver cancer patient malefemale practice purpose application analysis individual sample patient liver cirrhosis patient liver cancer treatment patient healed liver cancer treatment used primary sample group patient liver cirrhosis patient liver cancer treatment patient healed liver cancer treatment used secondary sample group preand posttreatment sample liver cancer taken patient sample following liver cancer patient included analysis method characterized serum sample taken liver cancer treatment liver cancer treatment carried tracking data followup data six month taken sample patient relapse transfer liver cancer completely cured recovered healthy example data mining selecting targeted candidate group target candidate group selected follows liver cancer early diagnosis protein marker candidate group ensured using liver atlas database currently associated liver disease comprehensive resource liver disease total number protein known associated liver disease liver atlas database protein secreted blood possibility secreted | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 44 | selected among protein based uniprot database result total protein selected finally order select detectable protein mass spectrometer protein peptide msms data exists selected using four different peptide msms library source nist iontrap nist qtof isb humanplasma home madebrary result total protein finally selected next selection target candidate group detected performed following manner practice order select detectable target candidate group using mass spectrometer peptide capable normally detecting signal selected mrm analysis sample normal group hcc group combined protein peptide finally selected example derivation target candidate population mrm analysis example preparation serum sample serum sample used experiment prepared following manner blood collected using bd vacutainer serum separation tube bd usa silica clot activator mlx mm product number phenylmethylsulfonyl fluoride pmsf added withdrawn blood finally reach mm approximately reverse phase mixing inverting mix cycle supernatant collected centrifugation c maintained rpm minute color observation hemolyzed red sample used mul supernatant dispensed ml eppendorf tube immediately placed ice dispensing followed labeling tube sample group labeled corresponding code eg nc mc pd etc mixture immediately stored step implemented ice block finished within one hour blood collection example depletion treatment serum protein order detect marker present low concentration blood following depletion process first carried namely six protein albumin igg iga haptoglobin transferin alphaantitrypsin present high abundance highabundant blood removed removing six major amount protein total protein mass mass removed blood protein corresponding remaining protein mass left remaining protein used analysis regarding consumption six protein blood largest amount bound adsorption column removed using mar multiple affinity removal system according method manufacturing company used analysis eluting protein present small amount bound example peptide formation serum protein serum sample obtained consumption procedure concentrated wk filter protein concentration quantified mean bca bicinchoninic acid analysis taking mug serum sample treatment performed urea final concentration mm dtt dithiothreitol tris ph followed minute propagation treatment mm final concentration iaa iodoacetamide propagation performed room temperature minute treatment carried mm tris hydroxymethyl aminomethane ph concentration urea le trypsin treatment performed ratio trypsin serum concentration propagation performed hour treatment performed concentration formic acid solution following desalting process performed example desalination serum protein activation performed dropping ml acn formic acid oasis adsorption column water usa three time equilibration equilibration performed dropping ml formic acid five time oasis adsorption column sample peptide added washed dropping ml formic acid five time peptide eluted treatment acn formic acid ml acn formic acid ml elution freezing one hour dried vacuum centrifugation speedvac analysis carried melting sample dried peptide mul sol buffer acn formic acid centrifuging rpm minute transferring mul glass vial example mrm analysis purpose mrm analysis order select target detected reproducibility technical reproducibility using protein peptide selected example exhibit expression difference normal group hcc group sample normal group combined posing three group normal group hcc group hcc group combined three group prepared repeated analysis performed using mrm three group described mrm analysis peptide fragment ion mrm analysis screened using skyline proteome g washington edusoftwareskyline target protein skyline open source software mrm method development analysis stergachis ab et al nat method nature method aforementioned protein sequence entered fasta format skyline designed peptide generate product ion list product ion list monitored mrm peptide filter condition used conversion selection follows maximum length peptide minimum length six amino acid excluding repeated arginine arg r lysine lys k methionine met also contained peptide methionine removed due deformability proline used even arginine lysine appears later proline used histidine h included although charge changed peptide satisfying condition used q conversion tetraploid quadrupule performs | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 45 | filter function pass specific q mz precursor ion precursor ion passing q filter singulated fragmentation decomposed daughter ion product ion tetraploid quadrupole collision cell due electric energy daughter ion specific daughter ion may passed tetraploid q performs filtering function like tetraploid q ion passing tetraploid q converted digital signal detector detector appear peak chromatogram relative absolute quantitative analysis performed analyzing peak area mrm analysis file containing information input analysis ab sciex usa analysis performed nonordered nonordered mrm method mrm result generated wiff wiffscan file transformed mzxml format using mzwiff input skyline mrm data processing thereby finding peak intensity mrm transition fig schematically show process mrms analyzed using specific peptide known concentration purpose quantitative assurance corresponding peptide referred internal standard peptide peptide amino acid containing isotope operation normalizing peak area value peptide study sample analyzed using lnvenpk heavylabeled heavylabeled peptide derived ecoli present human proteome galactosidase lacz operation normalizing peak area value target peptide obtained mrm analysis peak area value internal standard peptide performed injecting fmol internal standard peptide manner order perform semiquantitative semiquantitative mrm analysis protein detected reproducibility mass spectrometer mrmtechnique selected three repeated analysis group target cv value within selected least one two group normal group hcc group protein peptide selected using reproducible target thereafter order select target exhibiting expression difference normal group hcc group target object detected reproducibility pvalue assumed value foldchange level foldchange group confirmed normal distribution p value followed normalization test normalization test shaiprowilk target protein peptide reproducibility reproducibility analysis performed standalone ttest ttest parametric method normal distribution followed p value analysis performed mannwhitney test mannwhitney test nonparametric method case independent ttest pvalue confirmed dividing aligmnent test levens test leven test case following aligmnent pvalue case following pvalue whereby target confirmed target proteinpeptide exhibiting significant difference pvalue normal group hcc group independent ttest mantuttitest addition candidate population protein marker exhibiting pattern foldchange level normal group hcc group increased decreased fold selected thus confirmed protein pvalue le peptide present normal group hcc group protein fold change peptide present finally protein peptide selected target candidate group next confirm whether protein peptide selected unique peptide entire human proteome blast search program blastp search program ncbi used confirm whether peptide unique peptide thus protein equivalent nonunique peptide removed finally protein peptide finally selected target candidate group individual peptide presenting significant difference normal group hcc group example whether target candidate group marker confirms bloodendogenous peptide whether protein peptide selected example present blood confirmed following manner therefore confirmed whether peptide selected peptide present actual blood using stableisotope labeled standard si peptide corresponding protein sample obtained combining normal group hcc group together firing si peptide peptide located cterminal lysine lys k arginine arg r amino acid peptidec andfor nc andnsubstituted peptide peptide sequence therefore hydrophobicity eluted onto chromatogram time rt peptide blood see fig mrm analysis order confirm whether signal interference interference phenomenon occurs complex blood sample due peptide target peptide intensity pattern intensity pattern si peptide daughter ion q blood endogenous peptide confirmed fig order determine whether signal interference phenomenon generated relative ionic strength pvalue threshold blood intein si peptide compared using program automatic detection inaccurate inaccurate conversion whether peak area value cvthreshold blood intein si peptide detected prescribed manner time repetition measurement confirmed thus absence signal interference protein peptide finally selected blood endogenous target proteinspeptides quantified example confirmation blood endogenous peptide level shown example concentration | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 46 | target protein peptide present blood confirmed target quantitative target endogenous blood signal blood endogenous peptide signal synthetic si peptide complementary blood endogenous peptide confirmed together mrm analysis sample mixture si peptide sequentially diluted spot nm nm nm mixed mug sample normal group hcc group combined calculating relative ratio ratio using ion q interference phenomenon object separately obtaining peak area value peptide blood peak area value si peptide point complementary peptide multiplying relative ratio amount injected si peptide blood level target peptide finally confirmed see fig blood level peptide confirmed result confirmed protein lowest concentration serum islr immunoglobulin super proteinrich repeat protein immunoglobulin superfamily leucinerich repeat protein concentration fmol mug protein highest concentration amg alpha macroglobulin concentration pmol mug dynamic range x order fig result measurement concentration endogenous peptide blood confirmed blood concentration fmol mug small amount lowabundance target protein peptide medium amount middleabundance target protein peptide high amount highabundance target protein peptide measured fmol mug fig example derivation candidate population early diagnostic marker liver cancer application actual individual sample since patient liver cirrhosis diagnosed liver cancer classified highrisk group liver cancer present serological examination afp pivka ii used diagnosis liver cancer problem low diagnostic power sensitivity therefore protein quality showing difference liver cirrhosis patient liver cancer patient confirmed advance mrm method possible preselect patient early diagnosis progression liver cirrhosis patient liver cancer patient endogenous peptide examined blood used target injection concentration si peptide complementary endogenous peptide determined case small amount low abundance target blood level fmol g fmol si peptide uniformly injected case medium amount middleabundance target fmol g blood level fmol g amount si peptide blood peptide injected case large amount highabundance target blood level fmol g fmol si peptide uniformly injected case islr protein measured lowest level blood case si peptide injected fmol si peptide injected amount time higher level blood maximum case amg protein measured highest level blood case si peptide injected fmol si peptide injected amount lower level blood maximum fig described purpose early diagnosis respect finally examined target candidate group protein protein patient liver cirrhosis patient liver cancer patient liver cancer healed onset liver cancer used primary sample patient liver cirrhosis patient liver cancer patient liver cancer healed independently primary sample group used secondary sample thereby deriving marker diagnosing liver cancer exhibit three difference blinding way experimenter could confirm patient population mrm analysis performed random order analysis repeated three time sample normalizing normalization peak area value thus obtained respect target peptide peak area value peptide blood peak area value si peptide complementary thereto analysis performed ibm spss standard version graphpad version example single marker group deriving early diagnosis liver cancer since existing early diagnosis examination alphafetoprotein afp difficult distinguish chronic liver disease chronic hepatitis cirrhosis liver cancer thus used early diagnosis liver cancer comparison lc cirrhosis group hcc group target showing difference expression hcc group recovery recovery group state lc group liver cancer cured analyzed order provide new early diagnosis marker replacing alphafetoprotein result shown table purpose early diagnosis liver cancer single marker candidate group confirmation diagnostic power confirmation whether expression tendency independent sample group applied actual clinical field hospital confirmed marker high auc value confirmed result analysis primary sample training set result analysis secondary sample test set result finally confirmed significant difference p value ltoreq observed lc group hcc group hcc group recovery group | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 47 | protein peptide derived protein targeted high diagnostic ability auc value ltoreq result analysis primary sample training group result analysis secondary sample test group table table show target protein peptide auc value individual sample analysis trainingtest set following table red indicates case expression level increased comparison group blue indicates case expression level decreased table table example deriving multiple marker liver cancer shown example construction comparison multiple protein marker panel performed multivariate analysis multivariant analysis result primary analysis training set secondary analysis training set protein peptide exhibiting high diagnostic power lc group hcc group hcc group recovery group subject analysis binding one panel performed using logistic regression method one statistical analysis method result comparing lc group hcc group confirmed four peptide panel al itih thrb finc combination exhibiting highest diagnostic power two peptide panel thrb finc combination exhibiting highest diagnostic power hcc group recovery group specifically comparing lc group hcc group confirmed auc value confirmed four peptide panel make possible diagnose patient liver cirrhosis accuracy liver cancer patient among entire liver cancer patient accuracy liver cancer patient among liver cancer patient thus confirming diagnosis accuracy four peptide protein labeled panel fig furthermore remaining protein peptide added protein peptide confirmed numerous combination protein auc could produced hcc group recovery group compared auc value two confirmed peptide panel confirmed fig make possible diagnose patient liver cancer accuracy entire liver cancer patient accuracy entire postliver cancer treatment patient liver cirrhosis patient liver cancer patient thus diagnosis accuracy using two peptide marker panel confirmed remaining protein peptide added protein peptide confirmed numerous combination protein auc could produced example testing liver cancer marker using antibody marker present invention detected protein level detection method protein level includes mrm analysis analysis using antibody used present example intended object present invention obtained using one kind mrm analysis two kind method used reconfirmation reconfirmation antibody analysis analysis using antibody performed screening seven protein superior auc value protein verified mrm analysis peptide level marker diagnosis liver cancer table since antibody recognize antigen composed part residue whole protein hole protein antibody selection criterion peptide portion mrm analysis contained antibody immunogen portion close possible antibody result immunoblot assay plasmaserum preferentially selected well antibody monoclonal antigen present aap alphaantiplasmin antiplasmin mouse monoclonal ambp monoclonal afp alphafetoprotein mouse monoclonal fetua rabbitmonoclonal finc fibronectin iti interalphatryptophane residue heavy chain human intertrypsin inhibitor heavy chain mouse polyclonal itin intertrypsin inhibitor heavy chain rabbit h goat monoclonal plga plasminogenrelated protein human plasminogen activator rabbitpolyclonal thrb prothrombin rabbitmonoclonal immunoblotting performed using antibody described parenthesis santa cruz biotechnology usa therefore sample screened three group lc hcc recovery using independent sample group used primary secondary mrm analysis hccrecovery group sample screened stage stage initial stage liver cancer sample screened normalized od absorbance measured control group load control thereby correcting variation gel sdspage polyacrylamide gel electrophoresis control group mouse monoclonal mouse monoclonal antibody actin transferrin used result shown fig result indicate marker present invention analyzed variety protein analysis method next purpose applicationuse actual clinical practice elisa analysis protein level native form protein level native form performed one target protein finc highest discriminatory power among group immunoblot assay using abovedescribed antibody perform elisa assay sample screened three group lc hcc recovery using independent sample group used primary secondary mrm assay result analysis using elisa uscn life science inc korea kit one target protein according method production process expression state sample group uniform result mrm analysis immunoblot analysis auc value finally confirmed liver cirrhosis group liver cancer group compared liver cancer group liver cancer recovery group compared table fig result indicate marker present invention | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 48 | developed used various protein assay kit mrm immunoblot assay elisa table elisa assay information summary elisa assay result hcc group lc group v recovery group hcc group v claim use composition comprising detection reagent biomarker blood biomarker combination finc fibronectin thrb prothrombin igfals insulinlike growth factor binding protein complex acid labile subunit itihinter trypsin inhibitor heavy chain h combination finc fibronectin thrb prothrombin preparation diagnostic reagent diagnosis liver cancer liver cancer patient cirrhosis high risk group liver cancer use according claim wherein detection reagent reagent capable detecting biomarker based protein level use according claim wherein detection reagent protein level reagent immunoblotting test enzymelinked immunosorbent assay elisa radioimmunoassay immunodiffusion immunoelectrophoresis tissue immunostaining immunoprecipitation analysis complement fixation analysis fluorescence activated cell sorting facs mass analysis protein microarray use according claim wherein detection reagent protein level comprises antibody antibody fragment aptamer affinity multimer peptide mimetic receptor ligand cofactor specifically recognizes fulllength protein protein fragment biomarker cna biomarker liver cancer diagnosis application thereof active cnb en application claiming priority application number priority date filing date title kr kr kr kra krb en biomarker diagnosis liver cancer use thereof pctkr woa en biomarker diagnosis hepatoma use thereof publication publication number publication date cna cna en cnb true cnb en family id family application application number title priority date filing date cna active cnb en biomarker liver cancer diagnosis application thereof country status country link ep epa en kr krb en cn cnb en family citing family cited examiner cited third party publication number priority date publication date assignee title krb en use complement protein liver cancer diagnosis krb en biomarker monitoring detecting early onset liver cancer patient high risk liver cancer use cna en predicting kit risk hepatic cancer method krb en biomarker early diagnosis hepatocellular carcinoma precancerous lesion use thereof krb en hcc specific biomarkers cnb en application kit detecting soat protein expression level preparation hepatocellular carcinoma screening product krb en use itih detecting insulin resistance disease associated glucose intolerance krb en antibody specifically recognizing itih pharmaceutical composition comprising improving insulin resistance cnb en tumor marker heat shock factor binding protein liver cancer application thereof cnb en kit identifying benign malignant thyroid nodule cnb en liver cancer biomarker kit detecting liver cancer citation cited examiner cited third party publication number priority date publication date assignee title usa en national univeristy corporation hokkaido university method evaluating atherosclerotic lesion kit family cite family cited examiner cited third party publication number priority date publication date assignee title jpa en otsuka pharmaceut co ltd method detecting hepatocellular carcinoma woa en singapore health service pte ltd method predicting hepatocellular carcinoma recurrence determination hepatocellular carcinoma recurrenceassociated molecular biomarkers usa en jungyaw lin gene marker human hepatocellular carcinoma diagnosis cna en desgammacarboxyprothrombin microplate chemiluminescence immune analysis determination reagent kit preparing method thereof usb en morehouse school medicine exosomemediated diagnosis hepatitis virus infection disease usa en keio university liver disease marker method apparatus measuring method assaying pharmaceutical preparation kr kra patentkrben active ip right grant cn cna patentcnben active active ep epa patentepaen notactive withdrawn patent citation cited examiner cited third party publication number priority date publication date assignee title usa en national univeristy corporation hokkaido university method evaluating atherosclerotic lesion kit nonpatent citation cited examiner cited third party title association insulinlike growth factor insulinlike growth factor binding protein acidlabile subunit coronary heart diseasefrank fischer et alclinical endocrinology evaluation cystatin c fibronectin alphafeto protein biochemical marker patient liver diseaseselsaeid e elbawab et allife science journal also published publication number publication date epa en kra en cna en epa en krb en similar document publication publication date title cnb en biomarker liver cancer diagnosis application thereof krb en biomarker monitoring detecting early onset liver cancer patient high risk liver cancer use usb en apolipoprotein fingerprinting technique method related thereto aub en method marker diagnosis renal disease krb en marker diagnosis liver cancer woa en colorectal cancer metastasis detection method jpb en biomarkers detecting colorectal cancer usa en method marker diagnosis renal disease caa en composition method diagnosing ovarian cancer jpb en biomarker identification quantification | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 49 | ass risk preterm birth woa en biomarker panel barretts esophagus esophageal adenocarcinoma kra en identification quantification biomarkers evaluating risk preterm birth jimenez et al highthroughput targeted indepth mass spectrometrybased approach biofluid profiling biomarker discovery woa en biomarker diagnosis hepatoma use thereof krb en method screening cancer marker based deglycosylation glycoprotein marker hcc krb en marker diagnosing pancreatic cancer use krb en marker pancreatic cancer recurrence prognosis prediction use krb en protein biomarkers distinguishing malignancy intraductal papillary mucinous neoplasm use omenn et al human plasma serum proteome krb en biomarker detecting lupus nephritis use thereof krb en biomarkers predict tace treatment efficacy hepatocellular carcinoma krb en biomarker predict target drug efficacy hepatocellular carcinoma use kra en method marker diagnosis renal disease usb en biomarkers renal disease woa en method predicting rheumatoid arthritis treatment response legal event date code title description pb publication pb publication se entry force request substantive examination se entry force request substantive examination gr patent grant gr patent grant | 1710.06481 | biomarker liver cancer diagnosis application thereof | biomarker liver cancer diagnosis application thereof | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 50 | usa free ngal biomarker cancer google patent usa free ngal biomarker cancer google patent free ngal biomarker cancer download pdf info publication number usa usa u usa usa u u u u u u u u u authority u united state prior art keywords cancer ngal level free free ngal prior art date legal status legal status assumption legal conclusion google performed legal analysis make representation accuracy status listed abandoned application number u inventor marsha moses jiang yang current assignee listed assignee may inaccurate google performed legal analysis make representation warranty accuracy list childrens medical center corp original assignee childrens medical center corp priority date priority date assumption legal conclusion google performed legal analysis make representation accuracy date listed filing date publication date priority claimed usp externalpriority application filed childrens medical center corp filed critical childrens medical center corp priority u priority critical patentusaen assigned childrens medical center corporation reassignment childrens medical center corporation assignment assignor interest see document detail assignor yang jiang moses marsha publication usa publication critical patentusaen status abandoned legalstatus critical current link uspto uspto patentcenter uspto assignment espacenet global dossier discus cancer disease title claim abstract description biomarker substance title description lipocalin human gene claim abstract description lipocalin protein claim abstract description urine anatomy claim abstract description breast cancer disease claim abstract description ovarian cancer disease claim abstract description antibody protein claim description antibody human gene claim description malignant effect claim description prostate cancer disease claim description detectable effect claim description lung neoplasm malignant disease claim description lung cancer disease claim description basal cell carcinoma disease claim description cervix carcinoma disease claim description colon cancer disease claim description pancreatic carcinoma disease claim description renal cancer disease claim description cervical cancer disease claim description kidney cancer disease claim description preparation method method claim description radioactive effect claim description adenocarcinoma disease claim description bladder cancer disease claim description gastric cancer disease claim description lip andor oral cavity cancer disease claim description oesophageal carcinoma disease claim description renal cell carcinoma disease claim description small intestine carcinoma disease claim description esophageal cancer disease claim description fluorescent dye substance claim description gastric effect claim description lip cancer disease claim description liver cancer disease claim description monoclonal antibody protein claim description monoclonal antibody human gene claim description skin cancer disease claim description stomach cancer disease claim description urinary bladder cancer disease claim description metastatic cancer disease claim description ovary anatomy claim description enzymatic effect claim description spectrophotometry method method claim breast hyperplasia disease abstract description development method abstract description developmental process effect abstract description sample substance description cell anatomy description antigen substance description antigen human gene description antigen protein description gene expression effect description bioassay method description urinary effect description detection method method description method method description neoplasm disease description enzyme human gene description enzyme protein description carcinoma intraductal noninfiltrating disease description intraductal proliferative breast lesion disease description disease disease description ductal carcinoma situ disease description protein gene human gene description protein gene protein description substrate substance description solid phase substance description enzyme drug description matrix metalloproteinase human gene description matrix metalloproteinase protein description analyte substance description mass spectrometry method description diagnosis method description ion chemical class description lobular neoplasia disease description marker substance description secretion effect description desorption method description matrix material substance description radioimmunoassay method description antigenantibody complex protein description metastatic neoplasm disease description medium substance description membrane substance description metastastic effect description overexpression effect description therapeutic procedure method description western blot method description homo sapiens specie description membrane anatomy description analytical method method description mass spectrum method description organ anatomy description surfaceenhanced laser desorptionionisation method description tissue anatomy description elisa kit method description gapc protein description gapc protein description | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 51 | gapdg protein description gapdh protein description gapdh human gene description gapdh protein description mk protein description biological sample substance description cbbgc protein description conditioned culture medium substance description eg protein description gapdh protein description matrixassisted laser desorptionionisation method description substance substance description therapeutic effect description alkaline phosphatase protein description alkaline phosphatase human gene description breast anatomy description enzyme treatment wound ulcer drug description glb human gene description horseradish peroxidase protein description metastasis disease description mucin human gene description mucin protein description prostatespecific antigen human gene description prostatespecific antigen protein description tumour invasion disease description betagalactosidase protein description catabolic process effect description chemical reaction reagent substance description chemical substance application substance description competitive effect description compound chemical class description degradation effect description degradation reaction method description epithelial cell anatomy description manufacturing process method description metal inorganic material description metal substance description ovarian effect description ovarian disease disease description pancreatic cancer disease description pharmacologic agent substance description progressive effect description realtime pcr method description survival effect description tandem mass spectrometry method description ipjdhsycsqaodeuhfffaoysan chloromethylfluorescein chemical compound ococcccclccccccccoccoccocccococccc ipjdhsycsqaodeuhfffaoysan description agarose polymer description blood anatomy description elisa method description endometrial cancer disease description fab effect description hormone drug description raxxelzntbognwuhfffaoysan imidazole chemical compound ccncn raxxelzntbognwuhfffaoysan description immunoglobulin human gene description immunoglobulin protein description luciferase substance description luciferase family protein description muc human gene description qpcdcpdfjachgmuhfffaoysan nnbisbiscarboxymethylaminoethylglycine chemical compound ococnccooccnccooccnccooccoo qpcdcpdfjachgmuhfffaoysan description nitrocellulose substance description pentetic acid drug description unbound effect description urease protein description uterine cancer disease description assay kit method description bead substance description biopsy method description biosynthetic process effect description blood substance description cell invasion effect description chemoattractant effect description chemoattractant substance description chemotherapy method description densiometry method description kcxvzyzypllwccuhfffaoysan edta chemical compound ococnccooccnccooccoo kcxvzyzypllwccuhfffaoysan description engineering process method description entry host effect description evaluation method description formation reaction method description gene therapy method description genetic effect description highperformance liquid chromatographymass spectrometry method description hormone substance description immunoassay method description immunohistochemistry method description immunotherapy method description labelling method description laser desorption mass spectroscopy method description liquid substance description metal chemical class description migration effect description modification effect description modification reaction method description modifier substance description molecular probe substance description monomer substance description motility effect description nitrocellulos polymer description phase substance description polypeptide polymer description precipitating effect description prognosis method description quantitative analysis method description sodium dodecyl sulfate polyacrylamide gel electrophoresis method description solid substance description vaccine drug description hudplkwxrlnspcuhfffaoysan aminophthalhydrazide chemical compound ocnncoccccncc hudplkwxrlnspcuhfffaoysan description alb human gene description asparaginase drug description acetylcholinesterase drug description acetylcholinesterase protein description acetylcholinesterase human gene description adipose tissue anatomy description aggression disease description antibody binding site protein description anxiety disease description asparaginase protein description asparaginase human gene description brca human gene description brca protein protein description brca protein human gene description brca protein protein description basement membrane anatomy description bispecific antibody protein description blood vessel anatomy description breast cancer metastatic disease description catalase drug description cdh human gene description cdh protein description collagenase family human gene description collagenase family protein description igxwbgjhjzypqsssdottswsan dluciferin chemical compound ocochcsccsccccoccnn igxwbgjhjzypqsssdottswsan description disease progression disease description ductal carcinoma disease description ec human gene description ec protein description ec human gene description ec protein description ec protein description ec protein description ec human gene description epithelium anatomy description extravasation disease description fibronectins human gene description fibronectins protein description zfkjvjidpqddfyuhfffaoysan fluorescamine chemical compound cccccccooccoocccccccc zfkjvjidpqddfyuhfffaoysan description | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
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1710.06481 | 52 | glucose oxidase drug description glucan alphaglucosidase protein description glucose oxidase substance description glycerolphosphate dehydrogenase human gene description glycerolphosphate dehydrogenase protein description humanized monoclonal antibody human gene description humanized monoclonal antibody protein description isomerase human gene description isomerase protein description keratinocytes anatomy description tyqcgqrizgchnbjlaznsocsan lascorbic acid chemical compound occhochocococo tyqcgqrizgchnbjlaznsocsan description lipocalins human gene description lipocalins protein description lobular breast carcinoma situ disease description hwyhztirurjohguhfffaoysan luminol chemical compound ocnncocccnccc hwyhztirurjohguhfffaoysan description mgam human gene description myc human gene description malignant transformation disease description matrix metalloproteinases human gene description matrix metalloproteinases protein description micrococcal nuclease protein description mucin protein description nmr spectroscopy method description neoplasm progression disease description neutrophil anatomy description oryctolagus cuniculus specie description oxidoreductase human gene description oxidoreductase protein description peptidase human gene description peptidase protein description zwluxsqadudcsbuhfffaoysan phthalaldehyde chemical compound occcccccco zwluxsqadudcsbuhfffaoysan description phycocyanin protein description polystyrene substance description proteolytic enzyme treatment wound ulcer drug description renal injury disease description pywvycxtndrmgfuhfffaoysan rhodamine b chemical compound clccccnccccccocccncccccccccccccccoo pywvycxtndrmgfuhfffaoysan description ribonuclease human gene description ribonuclease protein description rosa specie description snai protein description saccharomyces cerevisiae specie description dwzajfzeyzihpouhfffaoysan santin natural product cccoccccccoccoccococcocco dwzajfzeyzihpouhfffaoysan description sepharose polymer description serum anatomy description serum albumin protein description singlechain antibody protein description singlechain antibody human gene description skin anatomy description squamous cell carcinoma disease description triosephosphate isomerase human gene description triosephosphate isomerase protein description vimentin human gene description vimentin protein description absorbing material substance description dzbuglkdjfmehcuhfffaoysao acridinehydron chemical class ccccccccccccnhc dzbuglkdjfmehcuhfffaoysao description adsorbent substance description allophycocyanin protein description alpha amino acid group chemical group description alteration effect description amino acid chemical class description angiogenesis inhibitor substance description angiogenesis inhibitor drug description antigenic effect description antineoplastic monoclonal antibody drug description atom chemical group description autoradiography method description bioluminescence method description bioluminescence effect description capillary electrophoresismass spectrometry method description capsule substance description cell motility effect description chemical reaction method description chemical reaction product substance description chimera protein description colorectal cancer disease description comedo carcinoma disease description conjugation effect description conventional method method description coupling effect description coupling process method description coupling reaction method description crystallographic characterization method description dependent effect description diagnostic evaluation method description differentiation effect description direct acting antiviral protease inhibitor drug description dye substance description effect effect description electrospray ionisation tandem mass spectrometry method description elution method description expression analysis method description extravasation effect description feeding blood organism effect description fibronectin effect description mhmnjmpurvtyejuhfffaoysan fluoresceinisothiocyanate chemical compound ococccncsccccccccoccocccoccc mhmnjmpurvtyejuhfffaoysan description fluorescent labelling method description fluorometric assay method description freezing method description gas chromatographymass spectrometry method description gentamicin protection assay method description glucose oxidase nutrition description health effect description imaging method method description immunocytochemistry method description immunoglobulin production effect description inhibitory effect effect description invasive ductal carcinoma disease description ischemic effect description laboratory method method description lanthanoid inorganic material description lanthanoid chemical class description lesion effect description liquid chromatography mass spectrometry method description luminiscence type method description lymphatic effect description mammography method description material substance description matrixassisted laser desorptionionisation timeofflight mass spectrometry method description menses anatomy description menstruation effect description migration assay method description mixture substance description modifying effect description monoclonal antibody drug description noncompetitive effect description partial effect description peptide hydrolase inhibitor substance description phage display method description phosphate substance description physical effect effect description plastic substance description plastic polymer description polystyrene polymer description polyvinyl chloride substance description polyvinyl chloride polymer description ozaifhulbgxakxuhfffaoysan precursor substance nccccnnccccn ozaifhulbgxakxuhfffaoysan description pregnancy effect description preventive effect description proteolythic effect description proteomic method description reactant substance description receptor human gene description receptor protein | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
"cs.CL",
"cs.AI"
] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1710.06481 | 53 | description reduced effect description regulatory effect description reverse transcription pcr method description sandwich elisa method description selection method method description sensitivity effect description shg protein description specie specie description spectrum method description substitution reaction method description thermography method description thyroid cancer disease description transcription effect description transcription factor protein description transcription factor human gene description transmembrane protein protein description transmembrane protein human gene description transport effect description tumor biomarker substance description tumor marker substance description ultrasonography method description unidentified phage specie description urinalysis method description visual effect effect description washing method description image classification gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite involving intracellular compound gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnspecifically defined cancer gnspecifically defined cancer breast gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnspecifically defined cancer gnspecifically defined cancer ovary gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite involving compound identifable body fluid gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gnassays involving biological material specific organism specific nature gnassays involving biological material specific organism specific nature animal human gnassays involving biological material specific organism specific nature animal human vertebrate gnassays involving protein known structure function defined subgroup abstract uncomplexed neutrophil gelatinase associated lipocalin ngal present increased level individual atypical ductal hyperplasia adh major risk factor future breast cancer development individual ovarian cancer individual breast cancer invasive noninvasive accordingly present invention directed measuring uncomplexed ngal level urine primary screen determine individual either risk developing developed cancer eg cancer epithelial origin including breast ovarian cancer description related application application continuation u application ser filed apr application continuation u application ser filed feb claim benefit usc e u provisional application filed feb entire content incorporated herein reference field invention invention relates noninvasive method diagnosis prognosis cancer eg cancer epithelial origin including breast ovarian cancer determining free ngal level urine sample obtained patient background invention one important factor survival cancer early stage detection clinical assay detect early event cancer offer opportunity intervene prevent cancer progression development gene profiling proteomics significant progress identification molecular marker biomarkers used diagnose prognose specific cancer example case prostate cancer psa prostate specific antigen detected blood indicative presence prostate cancer thus blood men risk prostate cancer quickly easily safely screened elevated psa level despite progress field cancer detection still remains need art identification new biomarkers variety cancer easily used clinical application particularly noninvasive method cancer screening urinalysis present probably patientfriendly option eg require phlebotomy widely used health care | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 54 | provider date appear option available diagnosing cancer manner polymorphic epithelial mucin muc transmembrane protein overexpressed ovarian cancer tumor expressed muc protein often cleaved circulation detectable tumor marker ca see eg bon et al clin chem however many patient tumor express muc serum ca level also reported associated ovarian cancer skakes cancer assessment level absolute indicator disease although roughly woman clinically apparent ovarian cancer increased level ca ca also increased first trimester pregnancy menstruation presence noncancerous illness cancer site expression gene neutrophil gelatinase associated lipocalin ngal lipocalin identified upregulated ovarian colon lung uterine cancer tumor tissue see eg wo wo u using gene expression analysis summary invention identifying biomarkers particularly relevant improving diagnosis prognosis treatment cancer eg cancer epithelial origin including breast ovarian cancer need art biomarkers quickly easily safely detected invention described herein utilizes biomarker free urinary neutrophil gelatinase associated lipocalin ngal diagnose stage monitor progression treatment subject cancer particular invasive potentially metastatic stage disease prior work field shown suggested reliable noninvasive way detect cancer eg epithelial origin including breast cancer ovarian cancer described herein uncomplexed free ngal found present increased level urine individual atypical ductal hyperplasia adh major risk factor future breast cancer development individual ovarian cancer individual breast cancer invasive noninvasive accordingly invention encompasses measuring uncomplexed urinary ngal primary screen determine individual either risk developing developed cancer eg epithelial origin ovarian prostate breast cancer cancer basal cell carcinoma renal cell carcinoma adenocarcinoma gastrointestinal cancer lip mouth esophageal small bowel stomach colon liver bladder pancreatic cervical lung skin kidney cancer method monitoring level urinary ngal marker therapeutic efficacy also disclosed embodiment invention includes method determining individual risk developing developed cancer level free ngal test urine sample obtained individual determined level compared control level free ngal level free ngal test sample higher control level free ngal indicates individual either increased risk developing cancer cancer another embodiment individual postcancer treatment patient level free ngal test sample higher control level free ngal postcancer treatment patient referred treatment recurrence cancer another embodiment cancer cancer epithelial origin eg breast cancer basal cell carcinoma adenocarcinoma gastrointestinal cancer lip cancer mouth cancer esophageal cancer small bowel cancer stomach cancer colon cancer liver cancer bladder cancer pancreas cancer ovary cancer cervical cancer lung cancer skin cancer kidney cancer prostate cancer renal cell carcinoma another embodiment level free ngal detected monomeric ngal another embodiment level free ngal detected includes monomeric ngal another embodiment antibodybased binding moiety eg monoclonal antibody preferentially bind free ngal form antibodyngal complex used presence antibodyngal complex detected measure level free ngal present antibodybased binding moiety may labeled detectable label radioactive label hapten label fluorescent label enzymatic label another embodiment invention includes method staging cancer level free ngal test urine sample obtained individual determined level compared control level free ngal level free ngal eg monomeric ngal test sample higher control level free ngal indicates individual either increased risk developing malignant metastatic cancer control level free ngal may associated healthy individual method directing treatment subject included also embodiment subject tested level free ngal urine sample obtained subject clinician review result urine higher level free ngal control level free ngal clinician directs subject tested cancer test may performed country subject resides another country result made available example via web site transmitted clinician method monitoring cancer risk cancer also disclosed level free ngal first test urine sample obtained individual obtain initial level free ngal determined level free ngal test urine sample compared level free ngal second urine sample obtained individual obtain second level free ngal subsequent urine collection comparison selected interval ie collect set data point done data point reviewed determine measured level free ngal test sample versus measured level free | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 55 | ngal control sample trend upward upward trend indicating cancer developing metastasizing individual ie second level greater first level individual may deemed greater risk developing cancer greater risk developing metastasizing cancer another embodiment individual postcancer treatment patient second level greater first level postcancer treatment patient referred treatment recurrence cancer kit detecting free ngal urine sample also disclosed kit include container holding urine sample least one antibody preferentially bind free ngal direction use kit may alternatively include least two antibody preferentially bind ngal one antibody immobilized solid phase antibody detectably labeled ngal found urine free ngal ie bound matrix metalloproteinase mmp complexed ngal ie ngalmmp complex method described herein free ngal measured one embodiment method determining individual risk developing developed cancer eg epithelial origin including breast ovarian cancer provided method comprises measuring level free complexed ngal present urine test sample comparing level obtained test sample control sample wherein higher level ngal urine test sample indicates individual either increased risk developing cancer already cancer positive result higher level therefore indicates individual tested cancer monitored accordingly preferably level free ngal fold preferably fold greater control level increase also detected control level invention advantageously used risk assessment early detection cancer eg cancer epithelial origin including breast ovarian cancer example subject screened physician annual physicals positive test result wherein level free ngal higher control would warrant diagnostic evaluation determine whether individual cancer precursor lesion cancer noted invention may also used ass level urinary free ngal present multiple test sample obtained patient progressive increase amount free ngal time indicates increased aggressiveness eg metastatic potential cancer ngal level serve predictor disease status stage embodiment ngal level assessed one interval monitor therapeutic efficacy treatment regime designed treat cancer eg cancer epithelial origin including breast ovarian cancer patient one aspect invention ngal level present test urine sample measured contacting test sample preparation thereof antibodybased binding moiety preferentially bind specifically free ngal protein portion thereof preferentially meant antibody bind free ngal rather ngal may complexed eg mmp embodiment free ngal monomeric ngal antibodybased binding moiety form complex ngal detected thereby allowing level ngal measured distinguish free ngal complexed ngal antibodybased binding moiety preferentially interacts free ngal used eg elisa antibodybinding moiety may raised epitope inside mmpngal binding region antibodybased immunoassay preferred mean measuring level ngal protein however mean known skilled art used ass ngal level example embodiment ngal expression level assayed mass spectrometry including seldi mass spectrometry brief description drawing accompanying drawing incorporated constitute part specification illustrate embodiment invention together description serve explain object advantage principle invention fig b show ngal transcript expression level ovarian cancer cell line expression level determined using realtime pcr fig show transcript separated agarose compared gapdh control transcript fig b graph depicting ratio ngalgapdh yaxis hose normal ovarian cell line ovcar ovcar skov ovarian cancer cell line fig graph illustrating amount ngal protein secretion conditioned medium ovarian cancer cell line ovcar ovcar skov determined borregaard elisa fig b show ngal transcript expression level breast cancer cell line expression level determined using realtime pcr fig show transcript separated agarose compared gapdh control transcript fig b graph depicting ratio ngalgapdh yaxis td mcf organ confined breast cancer cell line mdamb highly metastatic cell line fig graph illustrating amount ngal protein secretion conditioned medium breast cancer cell line td mcf mdamb determined borregaard elisa fig b show level ngal protein urine sample patient either disease benign ovarian disease malignant ovarian cancer fig show western blot analysis urine sample using antingal antibody fig b show quantitative analysis western blot described fig blot quantitated using densitometry level represented arbitrary densitometric unit fig amino acid sequence human ngal seq id fig graph ngal protein | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 56 | expression ovarian cancer urine sample compared healthy control sample determined borregaard elisa fig graph ngal protein expression breast cancer urine sample compared healthy control sample determined borregaard elisa fig graph ngal protein expression individual atypical ductal hyperplasia adh lobular carcinoma situ lcis major risk factor future breast cancer development compared level seen healthy individual r elisa used see example fig graph illustrating amount migrated cell per field yaxis migration assay breast cancer cell mcf cell express little ngal two cell line clone overexpress ngal n n fig graph illustrating amount cell invasion tumor invasion assay breast cancer cell mcf cell express little ngal two cell line clone overexpress ngal n n fig graph ngal protein expression individual atypical ductal hyperplasia adh major risk factor future breast cancer development ductal carcinoma situ dci common type noninvasive breast cancer invasive breast cancer ibc compared level seen healthy individual rd elisa used fig graph showing amount free ngal monomer present ovarian cancer urine sample patient normal benign malignant tumor malignant tumor sample evidence higher free ngal level benign sample population study carried ngal elisa kit dlcn available rd system minneapolis minn usa detailed description invention definition free ngal used interchangeably term uncomplexed ngal refers ngal complexed matrix metalloproteinase eg mmp cancer epithelial origin include cancer arise epithelial cell include limited breast cancer basal cell carcinoma adenocarcinoma gastrointestinal cancer lip cancer mouth cancer esophageal cancer small bowel cancer stomach cancer colon cancer liver cancer bladder cancer pancreatic cancer ovarian cancer cervical cancer lung cancer breast cancer skin cancer squamous cell basal cell cancer prostate cancer renal cell carcinoma known cancer effect epithelial cell throughout body cancer epithelial origin may hormonedependent cancer eg kidney breast endometrial ovarian prostate cancer control sample includes urine sample obtained normal healthy individual believed cancer control may selected using method well known art level become well established control population array result test urine sample directly compared known level preferably control sample age sex matched control urine sample control level level analyte tested level analyte compared control level empiricallydetermined mean median analyte level group individual believed disease interest eg cancer particular stage disease interest eg benign early stage cancer v malignant late stage cancer known analyte level actual sample eg positive control previouslydetermined analyte level particular individual eg monitoring individual two time point analyte example free ngal test sample includes urine sample obtained subject tested aggressive invasive includes proclivity tumor expanding beyond boundary adjacent tissue darnell j molecular cell biology third ed wh freeman ny invasive cancer contrasted organconfined cancer wherein tumor confined particular organ invasive property tumor often accompanied elaboration proteolytic enzyme collagenase degrade matrix material basement membrane material enable tumor expand beyond confines capsule beyond confines particular tissue tumor located metastasis includes condition spread cancer organ origin additional distal site patient process tumor metastasis multistage event involving local invasion destruction intercellular matrix intravasation blood vessel lymphatics channel transport survival circulation extravasation vessel secondary site growth new location see eg fidler et al adv cancer re liotta et al cancer treatment re nicolson biochim biophy acta zetter n eng j med increased malignant cell motility associated enhanced metastatic potential animal well human tumor hosaka et al gann haemmerlin et al int j cancer primary tumor includes tumor appearing first site within subject distinguished metastatic tumor appears body subject remote site primary tumor ngal includes ngal protein genebank accession genpept caa homo sapiens seq id fig ngal also referred neutrophil gelatinaseassociated lipocalin lipocalin ngal also encompasses specie variant homologues allelic form mutant form equivalent thereof term higher level used context comparison control sample test sample control level test sample level method disclosed herein includes level statistically significant significantly level found control sample eg fold higher fold higher preferably higher level least fold higher greater statistically significant significantly includes statistical significance generally mean two standard deviation sd normal higher concentration | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 57 | marker lcis lobular carcinoma situ lcis also called lobular neoplasia sometimes classified type noninvasive breast cancer penetrate wall lobule although usually become invasive cancer woman condition higher risk developing invasive breast cancer opposite breast dci ductal carcinoma situ ductal carcinoma situ common type noninvasive breast cancer dci malignant cell metastasized wall duct fatty tissue breast comedocarcinoma type dci likely type dci come back area lumpectomy closely linked eventual development invasive ductal carcinoma form dci increased risk cancer includes risk cancer increased general population person said increased risk cancer need monitoring development cancer continued presence cancer risk marker described detail disclosure cell line derived highly metastatic breast cancer mdamb express secrete higher amount ngal cell line derived benign organ defined breast cancer td mcf furthermore overexpression ngal ngal breast cancer cell line mcf induces mesenchymallike phenotype increase migration invasion regulates epithelial mesenchymal transition emt marker transcription expression indicating role ngal metastatic disease inventor discovered free urinary ngal used biomarker detect presence andor progression cancer eg cancer epithelial origin including breast ovarian cancer noninvasive assay test used essential part cancer diagnosis treatment patient concerned cancer diagnosis noninvasive nature test ameliorates somewhat apprehension associated process doctor care provider testing urine manner described herein rapid reliable method invention utilize standard methodology elisa obtain eg diagnosis cancer part course treatment therapeutic measure taken patient diagnosis treatment cancer determine whether cancer becoming aggressive metastasizing cancer include peritoneal cancer endometrial cancer cervical cancer colorectal cancer uterine cancer thyroid cancer lung cancer kidney cancer pancreatic cancer example determination likelihood cancer recurrence spread patient survival assist determining whether conservative radical approach therapy taken whether treatment modality combined example cancer recurrence likely advantageous precede follow surgical treatment chemotherapy radiation immunotherapy biological modifier therapy gene therapy vaccine like adjust span time patient treated ease speed invention enables insight decided advantage method disclosed herein may used determine whether individual cancer eg cancer epithelial origin including breast ovarian cancer increased risk developing cancer method involve measuring level free ngal test sample obtained individual comparing observed level control level free ngal eg found control sample control level defined level ngal higher control level indicate individual either increased risk developing cancer cancer level ngal represented arbitrary unit example unit obtained densitometer luminometer elisa plate reader purpose comparison test sample control sample type ie obtained urine however control sample also standard sample contains concentration ngal normally found urine sample obtained healthy individual urine sample preferably treated prevent degradation ngal protein method inhibiting preventing degradation include limited treatment sample protease inhibitor freezing sample placing sample ice preferably prior analysis sample constantly kept condition prevent degradation ngal protein one aspect invention secondary diagnostic step performed example level ngal found indicate either risk presence cancer additional method detecting risk cancer presence cancer performed confirm example ass risk cancer individual tested atypical ductal carcinoma adh lobular carcinoma situ lcis mean known art atypia breast diagnosed biopsy random periareolar fine needle aspiration ductal lavage genetic marker risk also assessed brca brca known genetic marker cancer variety additional diagnostic step used confirm presence cancer ultrasound mammography pet scanning mri thermal imaging imaging technique biopsy ductal lavage ductogram clinical examination method known skilled art patient increased risk cancer preferably placed cancer detection regime regular pap smear mammography assessment risk marker patient may also placed preventative regime administration angiogenesis inhibitor selective hormone receptor modulators preventive regime well known art patient cancer directed cancer treatment well known | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 58 | art additionally disease progression assessed following ngal level freengal level individual patient example change individual condition monitored comparing change ngal expression level individual time eg via standard method carrying longitudinal study patient relevant condition progressive increase ngal level indicative increased potential cancer tumor invasion metastasis andor later stage cancer depending upon reason monitoring individual time alternatively therapeutic efficacy treatment regimen monitored monitoring level ngal time individual example decrease ngal level time indicative efficacy treatment regimen longitudinal monitoring occur two time point method outlined previous paragraph may also advantageously used longitudinally monitor patient treated cancer eg recurrence cancer since urinary ngal eg free ngal found present disclosure useful cancer biomarker increased level urinary ngal patient posttreatment acted accordingly eg diagnosis treatment appropriate posttreatment patient control level urinary ngal would established eg using either one several value measured urinary ngal whichever analytically appropriate change posttreatment patient condition monitored comparing change ngal expression level individual needed depending condition appropriate patient patient population particular cancer progressive gradual increase rapid elevation urinary ngal level indicative recurrence determining cancer recurrence assist determining whether conservative radical approach therapy taken whether treatment modality combined cancer recurrence likely advantageous precede follow surgical treatment chemotherapy radiation immunotherapy biological modifier therapy gene therapy vaccine like adjust span time patient treated alternatively urinary free ngal level individual screened recurrence cancer compared empiricallydetermined control level test level individual greater control level indicates recurrence followed therapy monitoring described measuring level free urinary ngal free urinary ngal level may measured preferably use antibody antibody equivalent detect free ngal level method disclosed wo also suitable ngal level may also monitored mass spectrometric analysis one embodiment level ngal protein measured contacting urine sample antibodybased binding moiety preferentially bind free ngal fragment free ngal formation antibodyngal complex detected measure free ngal level antibodybased binding moiety antibody includes immunoglobulin molecule immunologically active determinant immunoglobulin molecule eg molecule contain antigen binding site preferentially bind immunoreacts ngal additional biomarkers invention antibodybased binding moiety includes whole antibody eg isotype igg iga igm ige etc fragment thereof also specifically reactive ngal protein preferably preferentially bind uncomplexed free ngal antibody fragmented using conventional technique thus term includes segment proteolyticallycleaved recombinantlyprepared portion antibody molecule capable selectively reacting certain protein nonlimiting example proteolytic andor recombinant fragment include fab fab fab fv dab single chain antibody scfv containing vl vh domain joined peptide linker scfvs may covalently noncovalently linked form antibody two binding site thus antibodybased binding moiety includes polyclonal monoclonal purified preparation antibody recombinant antibody term antibodybased binding moiety intended include humanized antibody bispecific antibody chimeric molecule least one antigen binding determinant derived antibody molecule preferred embodiment antibodybased binding moiety detectably labeled labeled antibody includes antibody labeled detectable mean include antibody enzymatically radioactively fluorescently chemiluminescently labeled antibody also labeled detectable tag cmyc ha vsvg hsv flag v diagnostic prognostic method invention use antibodybased binding moiety detection ngal level free ngal protein present urine sample correlate intensity signal emitted detectably labeled antibody one preferred embodiment antibodybased binding moiety detectably labeled linking antibody enzyme enzyme turn exposed substrate react substrate manner produce chemical moiety detected example spectrophotometric fluorometric visual mean enzyme used detectably label antibody present invention include malate dehydrogenase staphylococcal nuclease deltavsteroid isomerase yeast alcohol dehydrogenase alphaglycerophosphate dehydrogenase triose phosphate isomerase horseradish peroxidase alkaline phosphatase asparaginase glucose oxidase betagalactosidase ribonuclease urease catalase glucoseviphosphate dehydrogenase glucoamylase acetylcholinesterase chemiluminescence another method used detect antibodybased binding moiety detection may also accomplished using variety immunoassay example radioactively labeling antibody possible detect antibody use radioimmunoassay radioactive isotope detected mean use gamma counter scintillation counter autoradiography isotope particularly useful purpose present invention h c preferably also possible label antibody fluorescent compound fluorescently labeled | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 59 | antibody exposed light proper wave length presence detected due fluorescence among commonly used fluorescent labeling compound cye dye fluorescein isothiocyanate rhodamine phycoerytherin phycocyanin allophycocyanin ophthaldehyde fluorescamine antibody also detectably labeled using fluorescence emitting metal eu others lanthanide series metal attached antibody using metal chelating group diethylenetriaminepentaacetic acid dtpa ethylenediaminetetraacetic acid edta antibody also detectably labeled coupling chemiluminescent compound presence chemiluminescentantibody determined detecting presence luminescence arises course chemical reaction example particularly useful chemiluminescent labeling compound luminol luciferin isoluminol theromatic acridinium ester imidazole acridinium salt oxalate ester discussed free ngal level detected immunoassay enzyme linked immunoabsorbant assay elisa radioimmunoassay ria immunoradiometric assay irma western blotting immunohistochemistry described detail antibody array protein chip also employed see example u patent publication no u pat no immunoassay radioimmunoassay technique detecting measuring concentration antigen using labeled eg radioactively labeled form antigen example radioactive label antigen include h c concentration free ngal antigen biological sample measured antigen biological sample compete labeled eg radioactively antigen binding antibody antigen ensure competitive binding labeled antigen unlabeled antigen labeled antigen present concentration sufficient saturate binding site antibody higher concentration antigen sample lower concentration labeled antigen bind antibody radioimmunoassay determine concentration labeled antigen bound antibody antigenantibody complex must separated free antigen one method separating antigenantibody complex free antigen precipitating antigenantibody complex antiisotype antiserum another method separating antigenantibody complex free antigen precipitating antigenantibody complex formalinkilled aureus yet another method separating antigenantibody complex free antigen performing solidphase radioimmunoassay antibody linked eg covalently sepharose bead polystyrene well polyvinylchloride well microtiter well comparing concentration labeled antigen bound antibody standard curve based sample known concentration antigen concentration antigen biological sample determined immunoradiometric assay irma immunoassay antibody reagent radioactively labeled irma requires production multivalent antigen conjugate technique conjugation protein eg rabbit serum albumin rsa multivalent antigen conjugate must least antigen residue per molecule antigen residue must sufficient distance apart allow binding least two antibody antigen example irma multivalent antigen conjugate attached solid surface plastic sphere unlabeled sample antigen antibody antigen radioactively labeled added test tube containing multivalent antigen conjugate coated sphere antigen sample competes multivalent antigen conjugate antigen antibody binding site appropriate incubation period unbound reactant removed washing amount radioactivity solid phase determined amount bound radioactive antibody inversely proportional concentration antigen sample common enzyme immunoassay enzymelinked immunosorbent assay elisa elisa technique detecting measuring concentration antigen using labeled eg enzyme linked form antibody different form elisa well known skilled art standard technique known art elisa described method immunodiagnosis nd edition rose bigazzi ed john wiley son campbell et al method immunology w benjamin inc oellerich j clin chem clin biochem sandwich elisa antibody eg antingal antifree ngal linked solid phase ie microtiter plate exposed biological sample containing antigen eg ngal solid phase washed remove unbound antigen labeled antibody eg enzyme linked bound boundantigen present forming antibodyantigenantibody sandwich example enzyme linked antibody alkaline phosphatase horseradish peroxidase luciferase urease galactosidase enzyme linked antibody reacts substrate generate colored reaction product measured competitive elisa antibody eg antingal antifree ngal incubated sample containing antigen ie ngal antigenantibody mixture contacted solid phase eg microtiter plate coated antigen ie ngal antigen present sample le free antibody available bind solid phase labeled eg enzyme linked secondary antibody added solid phase determine amount primary antibody bound solid phase immunohistochemistry assay section tissue tested specific protein exposing tissue antibody specific protein assayed antibody visualized number method determine presence amount protein present example method used visualize antibody example enzyme linked antibody eg luciferase alkaline phosphatase horseradish peroxidase galactosidase chemical method eg dabsubstrate chromagen technique may used detect biomarkers | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 60 | invention according practitioner preference based upon present disclosure one technique western blotting towbin et proc nat acad sci wherein suitably treated sample run sdspage gel transferred solid support nitrocellulose filter detectably labeled antibody preferentially bind ngal eg antingal antifree ngal used ass ngal level intensity signal detectable label corresponds amount ngal present level quantitated example densitometry mass spectrometry addition ngal eg free ngal may detected using mass spectrometry malditof timeofflight selditof liquid chromatographymass spectrometry lcm gas chromatographymass spectrometry gcms high performance liquid chromatographymass spectrometry hplcms capillary electrophoresismass spectrometry nuclear magnetic resonance spectrometry tandem mass spectrometry eg msms msmsms esimsms etc see eg u publication no mass spectrometry method well known art used quantify andor identify protein see eg li et al tibtech rowley et al method kuster mann curr opin structural biol mass spectrometric technique developed permit least partial de novo sequencing isolated protein chait et al science keough et al proc natl acad sci usa reviewed bergman ex certain embodiment gas phase ion spectrophotometer used embodiment laserdesorptionionization mass spectrometry used analyze sample modern laser desorptionionization mass spectrometry ldims practiced two main variation matrix assisted laser desorptionionization maldi mass spectrometry surfaceenhanced laser desorptionionization seldi maldi analyte mixed solution containing matrix drop liquid placed surface substrate matrix solution cocrystallizes biological molecule substrate inserted mass spectrometer laser energy directed substrate surface desorbs ionizes biological molecule without significantly fragmenting however maldi limitation analytical tool provide mean fractionating sample matrix material interfere detection especially low molecular weight analytes see eg u pat no seldi substrate surface modified active participant desorption process one variant surface derivatized adsorbent andor capture reagent selectively bind protein interest another variant surface derivatized energy absorbing molecule desorbed struck laser another variant surface derivatized molecule bind protein interest contain photolytic bond broken upon application laser method derivatizing agent generally localized specific location substrate surface sample applied see eg u pat wo two method combined example using seldi affinity surface capture analyte adding matrixcontaining liquid captured analyte provide energy absorbing material additional information regarding mass spectrometer see eg principle instrumental analysis rd edition skoog saunders college publishing philadelphia kirkothmer encyclopedia chemical technology th ed vol john wiley son new york pp detection presence marker substance typically involve detection signal intensity turn reflect quantity character polypeptide bound substrate example certain embodiment signal strength peak value spectrum first sample second sample compared eg visually computer analysis etc determine relative amount particular biomolecules software program biomarker wizard program ciphergen biosystems inc fremont calif used aid analyzing mass spectrum mass spectrometer technique well known skill art person skilled art understands component mass spectrometer eg desorption source mass analyzer detect etc varied sample preparation combined suitable component preparation described herein known art example embodiment control sample may contain heavy atom eg c thereby permitting test sample mixed known control sample mass spectrometry run one preferred embodiment laser desorption timeofflight tof mass spectrometer used laser desorption mass spectrometry substrate bound marker introduced inlet system marker desorbed ionized gas phase laser ionization source ion generated collected ion optic assembly timeofflight mass analyzer ion accelerated short high voltage field let drift high vacuum chamber far end high vacuum chamber accelerated ion strike sensitive detector surface different time since timeofflight function mass ion elapsed time ion formation ion detector impact used identify presence absence molecule specific mass charge ratio embodiment relative amount one biomolecules present first second sample determined part executing algorithm programmable digital computer algorithm identifies least one peak value first mass spectrum second mass spectrum algorithm compare signal strength peak value first mass spectrum signal strength peak value second mass spectrum relative signal strength indication amount biomolecule eg ngal free ngal | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 61 | present first second sample standard containing known amount biomolecule analyzed second sample better quantify amount biomolecule present first sample certain embodiment identity biomolecules first second sample also determined one preferred embodiment biomarker level measured malditof mass spectrometry antibody free ngalbinding antibody use invention obtained commercial source example antifree ngal antibody available ngal elisa kit dlcn rd system minneapolis minn usa alternatively antibody raised free ngal portion biomarker polypeptide eg amino acid portion normally masked mmpngal complex order generate antibody interacts free ngal mmpngal antibodybinding moiety may raised epitope inside mmpngal binding region ordinary skill art need disclosed detail antibody use present invention produced using standard method produce antibody example monoclonal antibody production campbell monoclonal antibody technology laboratory technique biochemistry molecular biology elsevier science publisher amsterdam netherlands st groth et al j immunology kozbor et al immunology today antibody also readily obtained using antigenic portion protein screen antibody library phage display library method well known art example u pat wo disclose bacteriophage display library selection method producing antibody binding domain fragment ngal detection kit commercial kit detection prognostic evaluation ovarian cancer detection prognostic evaluation breast cancer provided according disclosure kit may configuration well known ordinary skill art useful performing one method described herein detection ngal kit convenient supply many essential reagent conducting assay detection ngal urine sample addition assay preferably performed simultaneously standard multiple standard included kit predetermined amount ngal protein result test quantitated validated kit include mean detecting ngal level ie ngal binding antibody antibody fragment selectively bind ngal protein diagnostic assay kit preferentially formulated standard twoantibody binding format one ngal specific antibody capture ngal patient sample another ngal specific antibody used detect captured ngal example capture antibody immobilized solid phase eg assay plate assay well nitrocellulose membrane bead dipstick component elution column second antibody ie detection antibody typically tagged detectable label calorimetric agent radioisotope one preferred embodiment kit comprises mean detecting level free ngal sample urine specific embodiment kit comprises dipstick antingal antibody fragment immobilized thereon preferentially bind ngal protein preferentially bound ngal protein detected using example second antibody detectably labeled colorimetric agent radioisotope whereupon amount free ngal may quantitatively determined ordinary skill art understand embodiment assay kit may employ limited following technique competitive noncompetitive assay radioimmunoassay ria bioluminescence chemiluminescence assay fluorometric assay sandwich assay immunoradiometric assay dot blot enzyme linked assay including elisa microtiter plate immunocytochemistry kit range sensitivity precision reliability specificity reproducibility assay established mean well known skilled art present invention illustrated following example example provided aid understanding invention construed limitation thereof example ngal urinary biomarker ovarian breast cancer example show free ngal serve biomarker cancer eg epithelial origin breast andor ovarian cancer moreover demonstrates free ngal useful diagnosing prognosing staging cancer fig b show ngal transcript expression level various ovarian cancer cell line fig b show ngal transcript expression level various breast cancer cell line expression level determined using realtime pcr result confirm ngal overexpressed cancer cell line compared noncancerous hose cell line fig show graph illustrating amount ngal protein secretion conditioned medium ovarian cancer cell line determined borregaard elisa described kjeldsen l koch c arnljots k borregaard n characterization two elisa ngal newly described lipocalin human neutrophil j immunol method nov using antingal antibody provided dr borregaard ovcar show highest level secretion skov significantly le secretion ovcar fig show graph illustrating amount ngal protein secretion conditioned medium breast cancer cell line using borregaard elisa mdamb cell line derived highly metastatic cancer show highest level ngal secretion significantly le secretion cell line derived organ confined cancer mcf td however inventor show data free urinary ngal protein serf biomarker breast andor ovarian cancer particular increase level free ngal urine sample patient malignant cancer | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 62 | compared control urine sample patient cancer level ngal protein urine sample patient either disease benign ovarian disease malignant ovarian cancer determined using western blot analysis fig b sdspage run reducing condition measuring free complexed ngal fig show western blot analysis urine sample using antihuman ngal rd system minneapolis minn usa fig b show quantitative analysis result least sample urine patient either disease benign ovarian disease malignant ovarian cancer patient malignant ovarian cancer showed higher amount ngal urine compared sample individual without disease confirmed borregaard elisa assay fig similar analysis urine sample breast cancer patient also showed higher level ngal urine patient malignant cancer compared patient without disease fig discovered individual atypical ductal hyperplasia adh major risk factor future breast cancer development higher level free ngal urine level seen healthy individual elisa assay us antingal antibody recognizes free ngal ngal elisa kit dlcn rd system minneapolis minn usa used ass level free ngal result shown fig using rd elisa increased level free ngal also detected individual ductal carcinoma situ dci common type noninvasive breast cancer invasive breast cancer ibc compared level seen healthy individual fig free ngal present urine least monomeric dimeric trimeric form detection free monomeric urinary ngal possible accordance present disclosure instance study carried ngal elisa kit dlcn rd system minneapolis minn usa presence monomeric ngal appears particularly indicative benign malignant ovarian cancer shown fig fig graph showing amount free ngal monomer present ovarian cancer urine sample patient benign malignant tumor comparison normal sample malignant tumor sample evidence much higher free ngal level benign sample population thus measuring level free ngal urine provides quick easy safe screen used determine whether individual either cancer eg epithelial origin breast andor ovarian cancer increased risk developing cancer higher level free ngal urine compared age sex matched control sample indicates individual either cancer increased risk developing breast andor ovarian cancer positive test indicates individual tested cancer monitored accordingly example ngal involvement epithelial mesenchymal transition emt epithelial mesenchymal transition emt important process epithelial cell acquire mesenchymal fibroblastlike property show reduced intercellular adhesion increased motility believed emtlike event occur tumor progression malignant transformation endowing cancer cell invasive metastatic property laruel et al oncogene ass potential role ngal development aggressive cancer prepared stable mcf cell line overexpress ngal n n mcf breast cancer cell line express little ngal found n n cell clone mcf cell overexpress ngal exhibit mesenchymallike phenotype cell lose cellcontacts scatter evenly across cell surface data shown migration ngal overexpressing cell evaluated using bd falcon hts fluoroblok multiwell insert system bd bioscience bedford mass according manufacture manual mcf control ngaloverexpressing cell nn grown confluence trypsinized resuspended serumfree medium cell seeded top chamber full medium l used chemoattractant added lower chamber incubation c co incubator hour medium removed upper chamber insert plate transferred new well plate containing mlwell celltracker cmfda molecular probe incubated hour c co bd fluoroblok membrane allows labeled cell migrated membrane visualized fluorescence microscope result assay clearly show overexpression ngal increase motility cell overexpressing ngal migrated parental mcf cell fig addition cell invasion stimulated overexpression ngal invasiveness ngal overexpressing cell evaluated using well bd biocoat tumor invasion system bd bioscience bedford mass according manufacture manual system fluoroblok membrane covered layer matrigel mcf control ngaloverexpressing cell nn grown confluence trypsinized resuspended serumfree medium cell seeded top chamber full medium l used chemoattractant added lower chamber incubation c co incubator hour medium removed upper chamber insert plate transferred new well plate containing mlwell celltracker cmfda molecular probe incubated hour c co bd fluoroblok membrane allows labeled cell invaded bd matrigel membrane visualized fluorescence microscope result assay show overexpression ngal increase invasiveness fig also assessed ability ngal regulate molecule known involved epithelial mesenchymal transition emt using rtpcr cell line overexpress ngal found overexpression ngal | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 63 | increase expression mesenchymal marker vimentin fibronectin data shown overexpression ngal reduces er ecadherin expression increase expression slug transcription factor regulates emt thus ngal involved development cell phenotype consistent found aggressive cancer equivalent skilled art recognize able ascertain using routine experimentation numerous equivalent specific procedure described herein equivalent considered within scope invention covered following claim various substitution alteration modification may made invention without departing spirit scope invention defined claim aspect advantage modification within scope invention content reference issued patent published patent application cited throughout application hereby incorporated reference appropriate component process method patent application document may selected invention embodiment thereof reference santin et al int j cancer gene expression profile primary ovarian serous papillary tumor normal ovarian epithelium identification candidate molecular marker ovarian cancer diagnosis therapy mishara et al j soc nephrol identification neutrophil gelatinase associated lipocalin novel early urinary biomarker ischemic renal injury obrien et al experimental dermatology neutrophil gelatinaseassociated lipocalin marker dysregulated keratinocyte differentiation human skin claim method determining individual risk developing developed cancer comprising step determining level free ngal test urine sample obtained individual b comparing level free ngal test urine sample control level free ngal wherein level free ngal test sample higher control level free ngal indicates individual either increased risk developing cancer cancer method claim wherein cancer cancer epithelial origin method claim wherein cancer epithelial origin selected group consisting breast cancer basal cell carcinoma adenocarcinoma gastrointestinal cancer lip cancer mouth cancer esophageal cancer small bowel cancer stomach cancer colon cancer liver cancer bladder cancer pancreas cancer ovary cancer cervical cancer lung cancer skin cancer kidney cancer prostate cancer renal cell carcinoma method claim wherein cancer breast andor ovarian cancer method claim wherein level free ngal detected comprises monomeric ngal method claim wherein level free ngal measured method comprising step contacting test sample preparation thereof antibodybased binding moiety preferentially bind free ngal form antibodyngal complex b detecting presence antibodyngal complex thereby measuring level free ngal present method claim wherein antibodybased binding moiety labeled detectable label method claim wherein label selected group consisting radioactive label hapten label fluorescent label enzymatic label method claim wherein antibodybased binding moiety antibody method claim wherein antibody monoclonal antibody method claim comprising step reviewing result urine higher level free ngal control level free ngal directing individual tested cancer method claim wherein level free ngal measured mass spectrophotometric method method claim wherein individual postcancer treatment patient level free ngal test sample higher control level free ngal postcancer treatment patient referred treatment recurrence cancer method staging cancer comprising step determining level free ngal test urine sample obtained individual b comparing level free ngal test urine sample control level free ngal wherein level free ngal test sample higher control level free ngal indicates individual either increased risk developing malignant metastatic cancer method claim wherein free ngal comprises monomeric ngal method claim wherein control level level free ngal associated healthy individual canceled method monitoring cancer risk developing cancer individual comprising step determining level free ngal first test urine sample obtained individual obtain first level free ngal b determining level free ngal second urine sample obtained individual obtain second level free ngal c comparing first second level free ngal method claim wherein second level greater first level individual greater risk developing cancer greater risk developing metastasizing cancer method claim wherein individual postcancer treatment patient second level greater first level postcancer treatment patient referred treatment recurrence cancer canceled u free ngal biomarker cancer abandoned usa en priority application application number priority date filing date title u usa en free | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 64 | ngal biomarker cancer application claiming priority application number priority date filing date title usp u usa en free ngal biomarker cancer u usa en free ngal biomarker cancer u usa en free ngal biomarker cancer u usa en free ngal biomarker cancer u usa en free ngal biomarker cancer u usa en free ngal biomarker cancer related parent application application number title priority date filing date u continuation usa en free ngal biomarker cancer publication publication number publication date usa true usa en family id family application application number title priority date filing date u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer family application application number title priority date filing date u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer u abandoned usa en free ngal biomarker cancer country status country link u usa en ep epb en jp jpa en cn cna en au aua en ca caa en wo woa en family citing family cited examiner cited third party publication number priority date publication date assignee title woa en childrens medical center corporation noninvasive enzyme screen tissue remodellingassociated condition woa en antibodyshop determination neutrophil gelatinaseassociated lipocalin ngal diagnostic marker renal disorder epb en childrens medical center corporation free ngal biomarker cancer usa en kristian bangert method device rapid assessment severity injury usa en krusz john c medical treatment modality headache pain medical disorder usb en university hong kong use lipocalin diagnostic marker therapeutic target woa en bioporto diagnostics diagnostic test renal injury woa en dublin city university diagnostic prognostic andor predictive indicator breast cancer caa en abbott laboratory glycosylated mammalian ngal use thereof usb en abbott laboratory antibody bind mammalian ngal us thereof cna en diagnostic use individual molecular form biomarker epa en univ columbia high molecular weight ngal biomarker chronic kidney disease jpa en nationa hospital organization compositionkit method testing disease accompanying ageing blood vessel disorder usa en abbott laboratory isolated human autoantibody neutrophil gelatinaseassociated lipocalin ngal method kit detection human autoantibody ngal woa en abbott laboratory neutrophil gelatinaseassociated lipocalin ngal protein isoforms enriched urine recombinant chinese hamster ovary cho cell related composition antibody method enrichment analysis use krb en method device kit detecting monitoring acute kidney injury usa en jonathan barasch use urinary ngal distinguish kidney disease predict mortality subject cirrhosis woa en fred hutchinson cancer research center method kit detecting ovarian cancer blood epa en stichting katholieke universiteit method predicting outcome chemotherapy ovarian cancer woa en trustee columbia university city new york use urinary ngal diagnose sepsis low birth weight infant usa en abbott laboratory method assaying urinary neutrophil gelatinaseassociated lipocalin ungal prognosis cadaveric kidney transplant function patient including patient diagnosed delayed graft function dgf method assaying ungal assessment risk dgf patient diagnosed early graft function egf related kit cna en method detecting neutrophil gelatinaseassociated lipocalin ngal sample woa en trustee columbia university city new york ngal urinary tract infection jpa en ngal protein variant us thereof cnb en detection kit latex particle enhanced neutrophil gelatinaseassociated lipid transfer protein epb en trustee columbia university city new york mutant ngal protein us thereof usb en koninklijke philip nv diagnostic method employing hnl jpb en skin viscoelastic marker use thereof gbd en univ london queen mary biomarkers pancreatic cancer cna en kit specific detection lip cancer epb en hirotsu bio science inc method detecting proliferation cancer cancer patient cnb en oligopeptide pharmaceutical application cnb en synthetic oligopeptides us thereof cnb en synthetic oligopeptide inhibiting lung cancer metastasis cnb en | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 65 | oligopeptide preventing treating lung cancer metastasis cnb en antihuman ngal antibody application thereof detection test paper card cnb en antihuman neutrophil gelatinaseassociated lipocalin antibody application thereof detection test paper card cnb en special urine protein composite quality control material preparation method thereof family cite family cited examiner cited third party publication number priority date publication date assignee title gbb en finnigan mat gmbh process device laser desorption analyte molecular ion especially biomolecules usa en rockefeller university instrument method laser desorption ion mass spectrometry est en baylor college medicine method spectrometer mass desortion ionization analyts woa en oy medix biochemica ab method test kit diagnosis periodontal disease predicting risk progression thereof usa en united state america represented department health human service phagedisplay immunoglobulin heavy chain library jpa en noninvasive enzyme screen condition associated tissue remodeling nza en ciphergen biosystems inc retentate chromatography apparatus application biology medicine usb en zyomyx incorporated protein array highthroughput screening usb en cytyc health corporation identifying material breast duct woa en viventia biotech inc enhanced phage display library human vh fragment method producing usb en hypromatrix inc method array detecting biological molecule woa en childrens medical center corporation noninvasive enzyme screen tissue remodellingassociated condition woa en millennium pharmaceutical inc nucleic acid molecule protein identification assessment prevention therapy ovarian cancer epa en ciphergen biosystems inc biomolecule characterization using mass spectrometry affinity tag usb en brigham woman hospital inc detection ovarian cancer based upon alphahaptoglobin level epa en eos biotechnology inc method diagnosis ovarian cancer composition method screening modulators ovarian cancer usb en pdl biopharma inc method diagnosis ovarian cancer composition method screening modulators ovarian cancer usa en milagen inc information enhanced antibody array ila en beyond genomics inc method system profiling biological system woa en millipore corporation sample preparation biological fluid proteomic application usa en prasad devarajan method kit detecting early onset renal tubular cell injury epb en childrens medical center corporation free ngal biomarker cancer ep epa patentepben active active au aua patentauaen notactive abandoned ep epa patentepaen notactive withdrawn cn cnaa patentcnaen active pending jp jpa patentjpaen notactive withdrawn ca caa patentcaaen notactive abandoned u u patentusaen notactive abandoned wo pctus patentwoaen active application filing u u patentusaen notactive abandoned u u patentusaen notactive abandoned u u patentusaen notactive abandoned u u patentusaen notactive abandoned u u patentusaen notactive abandoned also published publication number publication date cna en woa en usa en epa en usa en woa en usa en caa en usa en aua en epb en usa en jpa en epa en similar document publication publication date title usa en free ngal biomarker cancer usa en cyr biomarker diagnosis prognosis cancer epithelial origin usa en method diagnosis prognosis epithelial cancer usa en adamts biomarker cancer epithelial origin jpb en method diagnosing prognosing cancer epithelial origin woa en method diagnosis prognosis epithelial cancer legal event date code title description assignment owner name childrens medical center corporation massachuset free format text assignment assignor interestassignorsmoses marsha ayang jiangsigning date reelframe stpp information status patent application granting procedure general free format text docketed new case ready examination stpp information status patent application granting procedure general free format text non final action mailed stcb information status application discontinuation free format text abandoned failure respond office action | 1710.06481 | free ngal biomarker cancer | free ngal biomarker cancer | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 66 | usb method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof google patent usb method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof google patent method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof download pdf info publication number usb usb u usa usb u b u b u b u u u u b u b u b authority u united state prior art keywords patient ilrb index patient mdk prior art date legal status legal status assumption legal conclusion google performed legal analysis make representation accuracy status listed active application number u version usa en inventor david darling james miller suttie mark dalphin laimonis kavalieris paul osullivan satish kumar current assignee listed assignee may inaccurate google performed legal analysis make representation warranty accuracy list pacific edge ltd original assignee pacific edge ltd priority date priority date assumption legal conclusion google performed legal analysis make representation accuracy date listed filing date publication date priority claimed usp externalpriority application filed pacific edge ltd filed critical pacific edge ltd publication usa publication critical patentusaen assigned pacific edge limited reassignment pacific edge limited assignment assignor interest see document detail assignor kumar satish dalphin mark darling david kavalieris laimonis suttie james miller osullivan paul priority u priority critical patentusaen application granted granted critical publication usb publication critical patentusben assigned pacific edge limited reassignment pacific edge limited assignment assignor interest see document detail assignor kumar satish dalphin mark darling david kavalieris laimonis suttie james osullivan paul status active legalstatus critical current anticipated expiration legalstatus critical link uspto uspto patentcenter uspto assignment espacenet global dossier discus genetic effect title claim abstract description transitional cell carcinoma disease title claim description biomarker substance title description gene expression effect claim abstract description hoxa human gene claim abstract description hoxa protein claim abstract description cdk protein claim abstract description cdk protein claim abstract description cdkap protein claim abstract description pold protein claim abstract description pol protein claim abstract description smoking effect claim abstract description ribonucleotidesnm polymer claim description urine anatomy claim description mixture substance claim description urinary bladder anatomy claim description rbc anatomy claim description inflammatory condition effect claim description interleukin protein claim description erythrocyte anatomy claim description cdc protein claim description interleukin receptor human gene claim description interleukin receptor protein claim description cdk human gene claim description lab test method claim description midkine human gene claim midkine protein claim insulinlike growth factor binding protein human gene claim insulinlike growth factor binding protein protein claim cdc protein kinase human gene claim cdc protein kinase protein claim antiinflammatory agent substance claim antiinflammatory agent drug claim hematuria disease abstract description mdk protein abstract description cancer disease abstract description igfbp human gene abstract description igfbp protein abstract description work procedure method abstract description pold human gene abstract description mdk human gene abstract description diagnostic procedure method abstract description bladder cancer disease description urinary bladder cancer disease description sample substance description marker substance description sensitivity effect description detection method method description analytical method method description antibody human gene description antibody protein description neoplasm disease description protein gene human gene description protein gene protein description disease disease description tissue anatomy description cell anatomy description method method description deoxyribonucleic acid polymer description logistic regression method description bioassay method description malignant effect description diagnosis method description messenger rna protein description calculation algorithm method description messenger rna polymer description inflammatory effect description oligonucleotide polymer description urinary tract infection disease description elisa method description urinary bladder disease disease description acute cystitis disease description bladder disease disease description polypeptide polymer description product substance description urinary bladder neoplasm disease description amplification effect description cystoscopy method description evaluation method description hybridization method description nucleic acid amplification method method description realtime pcr method description interleukin human gene description chemical reaction method description complementary dna substance description inflammatory disease disease description complementary dna polymer description serum anatomy description effect effect description | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 67 | increased effect description numa human gene description clinical urine test method description nuclear matrix protein protein description complementary dna protein description cdna synthesis method description cystitis disease description developmental process effect description polynucleotide polymer description reverse transcription pcr method description neutrophil anatomy description binding effect description development method description polynucleotide substance description prostate anatomy description bead substance description monoclonal antibody protein description corresponding effect description dye substance description zhnuhdyfzuaesouhfffaoysan formamide chemical compound nco zhnuhdyfzuaesouhfffaoysan description microarray method description fapwrfpifsizltuhfffaoysam sodium chloride chemical compound nacl fapwrfpifsizltuhfffaoysam description solid substance description inflammation disease description nucleic acid sequence polymer description urinary tract anatomy description chemical reaction reagent substance description crossvalidation method description inflammatory process effect description monoclonal antibody human gene description quantification method description substrate substance description washing method description cxcr protein description cxcr human gene description calculus urinary disease description urine test drug drug description urolithiasis disease description engineering process method description immune serum protein description dependent effect description interaction effect description preparation method method description proteomic method description sodium chloride substance description solution substance description pjvwktkqmonhtiuhfffaoysan hydroxyoxophenylbutylbenzopyranone chemical compound occcccccococcccoccccccc pjvwktkqmonhtiuhfffaoysan description body fluid anatomy description plasma anatomy description rna extraction method description taq polymerase protein description warfarin drug description accumulation method description antigen substance description antineoplastic monoclonal antibody drug description body fluid substance description complement effect description malignancy effect description measurement method description monoclonal antibody drug description prostate disease disease description statistical method method description tumor marker substance description blood anatomy description ervk human gene description nuc protein description skin exfoliation disease description hrxkrngnammehjuhfffaoysak trisodium citrate chemical compound nananaococcoccoocoo hrxkrngnammehjuhfffaoysak description antigen human gene description antigen protein description blood substance description uiimbognxhqvgwuhfffaoysam buffer substance naocoo uiimbognxhqvgwuhfffaoysam description computed tomography method description fluid substance description nuca protein description partition method description proliferation effect description purification method description quality control method method description trisodium citrate substance description tumor cell anatomy description type analysis method description validation analysis method description vascular effect description benign prostatic hyperplasia disease description bikinia letestui specie description blood cell anatomy description ec protein description metastasis disease description osteopontin human gene description osteopontin protein description dbmjmqxjhonafjuhfffaoysam sodium laurylsulphate chemical compound naccccccccccccosooo dbmjmqxjhonafjuhfffaoysam description addition method description data analysis method description detectable effect description distribution method description drug substance description exfoliation method description gel substance description health effect description immunohistochemistry method description investigational therapy method description isolation method description manufacturing process method description membrane substance description molecular cloning method description response effect description reverse transcription method description segregation method description separation method method description sodium citrate substance description aulopiformes specie description enzyme drug description enzyme human gene description enzyme protein description fab effect description hyperplasia disease description inflammatory cell anatomy description intron polymer description klk human gene description malignant melanoma disease description oligonucleotide probe protein description oligopeptides human gene description oligopeptides protein description ovarian cancer disease description prostate cancer disease description prostatespecific antigen protein description tac drug description thyroglobulin human gene description thyroglobulin protein description thyroglobulin drug description adjuvant substance description adjuvant effect description alpha amino acid group chemical group description biological sample substance description blocking effect description cleaning method description correlated effect description densiometry method description disease infectious agent disease description drug drug description expression analysis method description glycosylation effect description glycosylation reaction method description immune effect effect description immunoblotting method description immunogen effect description magnetic resonance imaging method description melanoma disease description | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 68 | melting method description mucosa anatomy description oligonucleotide probe substance description optimization method description polyacrylamide polymer description polyclonal antibody protein description recurrent effect description reduced effect description repetitive effect description research method description salmon nutrition description sampling method description secretion effect description smoke substance description sodium phosphate substance description sodium phosphate inorganic material description solvent extraction method description survival effect description thyroid cancer disease description ryfmwsxoazqypiuhfffaoysak trisodium phosphate chemical compound nananaopooo ryfmwsxoazqypiuhfffaoysak description adenocarcinoma pancreas disease description agarose polymer description alkaline phosphatase human gene description alkaline phosphatase protein description amplicon polymer description best practice method description brain anatomy description breast cancer disease description cerebrospinal fluid anatomy description coding region polymer description creatinine drug description dextran sulfate drug description dysuria disease description immunoglobulin human gene description immunoglobulin protein description zpnfwupytfpojulpysrvmusan iniprol chemical compound cchconcconcconchcsscchconchccccnconchcconchcccncnnconchcnchconchcccncnnconchcccccoccconchcccccccconchcccccoccconchccnoconchcconchccccnconchcconcconchccccconchcsscchncochccooncochcccooncochcncochconcochccccnncochcccccccncochccnoncochccnoncochcccncnnncochccccnncochcncochcccncnnncoconchccscconchcccncnnconchchcoconchcsscchncochcccccccncochccooncochnccccochncccncnnconchccccconchcccooconchcccconchcccconchcccccoccconchchcoconcconchcccconconcconcconchccooconchcccnoconchconchcccccccconchconcccchcochcccochcccccccocc zpnfwupytfpojulpysrvmusan description kidney calculus disease description liver anatomy description lymph node anatomy description nephrolithiasis disease description nucleic acid probe protein description nylon substance description abnormal effect effect description apoptogenic effect description biosynthetic process effect description byproduct substance description calculation method method description cell culture method description cell growth effect description chimera protein description ddrjaanprjihgjuhfffaoysan creatinine chemical compound cncconcn ddrjaanprjihgjuhfffaoysan description crystallographic characterization method description daily effect description deoxyribonucleotide substance description deoxyribonucleotide group chemical group description detergent substance description enhancing effect description entry host effect description flow cytometry method description fluorescence spectroscopy method description fluorescent dye substance description gastric effect description immunoprecipitation method description situ hybridization method description vitro method description incorporation method description inhibin substance description ligand substance description mrna extraction method description metabolite substance description microarray analysis method description normalization method description nucleic acid probe substance description nucleic acid chemical class description nucleotide substance description nylon polymer description organ anatomy description overexpression effect description pancreatic adenocarcinoma disease description paraffin wax substance description phage display method description phosphate buffered saline substance description polymerase chain reaction method description poor prognosis method description quantitative reverse transcription pcr method description quenching effect description radioactive effect description radioimmunoassay method description salt chemical class description suspension substance description thyroid carcinoma disease description ultrasonography method description urinalysis method description urinary effect description western blot method description bacyuwvyytxetduhfffaoysan dodecanoylmethylaminoacetic acid chemical compound cccccccccccconcccoo bacyuwvyytxetduhfffaoysan description srrna precursor polymer description alb human gene description ambp protein description ambp human gene description adenocarcinoma disease description antibiotic throat preparation drug description antibiotic treatment hemorrhoid anal fissure topical use drug description antibiotic systemic use drug description antitubercular antibiotic drug description anxiety disease description anxiety disease disease description ascitic fluid anatomy description asymptomatic bacteriuria disease description average auc effect description avian myeloblastosis virus specie description bladder transitional cell anatomy description bos taurus specie description bovine serum albumin drug description bovine serum albumin protein description breast anatomy description ceacam human gene description aiyuhdojvyhvituhfffaoysam caesium chloride chemical compound clcs aiyuhdojvyhvituhfffaoysam description canis lupus familiaris specie description carcinoembryonic antigen protein description cell membrane anatomy description cervidae specie description chondrichthyes specie description colon anatomy description cytokine human gene description cytokine protein description dna primer substance description dna probe substance description dnadirected dna polymerase protein description dnadirected dna polymerase human gene description doublestranded rna protein description endonuclease protein description equidae specie description erectile dysfunction disease description escherichia coli specie description zmmjgeglrurxtfuhfffaoysan ethidium bromide chemical compound brcccncccccccnccnccccccccc zmmjgeglrurxtfuhfffaoysan description felis catus specie description gilx protein description gastric cancer disease description glycoside hydrolases human gene description glycoside hydrolases protein description zjyyhgljygjllnuhfffaoysan guanidinium thiocyanate chemical compound scnncnn zjyyhgljygjllnuhfffaoysan description gynecological antibiotic drug description hspb human gene | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 69 | description hspb protein description hspb protein description hva protein description haemorrhage disease description homo specie description horseradish peroxidase protein description human protein protein description human protein human gene description hybridoma anatomy description increase auc effect description ugqmrvrmyyaskqkqynxxcusan inosine chemical compound ochchochcoochncncncocnc ugqmrvrmyyaskqkqynxxcusan description ugqmrvrmyyaskqkmpdegcqsan inosine natural product ochchochcoochncncncocnc ugqmrvrmyyaskqkmpdegcqsan description intron protein description klk protein description klk human gene description kidney anatomy description kidney disease disease description lea protein description lec protein description lecc protein description lecg protein description lect protein description line retrotransposable element orf protein human gene description lung anatomy description lung neoplasm malignant disease description lymph anatomy description mmp human gene description male sexual dysfunction disease description mammalia specie description mannwhitney u test method description matrix metalloproteinase protein description matrix metalloproteinase human gene description matrix metalloproteinase protein description matrix metalloproteinase human gene description matrix metalloproteinase protein description maximum likelihood method description metastasis central nervous system disease description metastatic neoplasm disease description moloney murine leukemia virus specie description monoplex specie description muscle anatomy description nitrocellulose substance description northern blotting method description nuclear matrixassociated protein protein description nuclear matrixassociated protein human gene description geyoculixldcmwuhfffaoysan ophenylenediamine chemical compound nccccccn geyoculixldcmwuhfffaoysan description occupational exposure disease description oryctolagus cuniculus specie description osg protein description ovary anatomy description ovis specie description pcr kit method description pcr analysis method description pancreas anatomy description papilloma disease description peptidase protein description peroxidase drug description peroxidase protein description peroxidase human gene description polysorbate polymer description prostatic haemorrhage disease description protease substance description ribonucleotide polymer description scorpiones specie description serum albumin protein description singlestranded dna protein description spleen anatomy description squamous cell carcinoma disease description stomach anatomy description suidae specie description qaowncqodcnurduhfffaoysan sulfuric acid chemical compound osooo qaowncqodcnurduhfffaoysan description timp protein description testis anatomy description fqenqntwsfedliuhfffaoysaj tetrasodium pyrophosphate chemical compound nanananaopooopooo fqenqntwsfedliuhfffaoysaj description thymus gland anatomy description topical antifungal antibiotic drug description tth polymerase protein description unbound effect description urethral stenosis disease description urinary bladder calculus disease description urinary calculus disease description urinary tract inflammation disease description urologic disease disease description uterus anatomy description xeno protein description abdominal effect description absorbance method description addition reaction method description additional effect description animal cell anatomy description annealing method description anti bacterial agent substance description antisense effect description anxiety effect description aromatic amine chemical class description assay kit method description biocidal effect description bioinformatics method method description biopsy method description ybjhbahktgyvgtzkwxmuahsan biotin chemical compound nconchchcccccooscch ybjhbahktgyvgtzkwxmuahsan description biotin drug description biotin nutrition description biotin substance description bleeding effect description bleeding toxicity description blood count method description catabolic process effect description ccdb protein description cell death effect description cell proliferation effect description cellular effect description cesium chloride drug description chemical engineering method description chemical substance application substance description chronic kidney disease disease description cigarette nutrition description clinical diagnostic method method description colorectal cancer disease description comparative analysis method description comparative effect effect description competitive effect description compound chemical class description concentrate substance description constituent substance description contamination method description conventional method method description cutting process method description deficient effect description densitygradient centrifugation method description detrimental effect description diagnostic biomarker substance description diagnostic imaging method description shibstmrcdjxlnkczcntnesan digoxigenin chemical compound cchccccochchccccchocchcccchocccooc shibstmrcdjxlnkczcntnesan description diluted sample substance description dilution method description kcxvzyzypllwccuhfffaoysan edta chemical compound ococnccooccnccooccoo kcxvzyzypllwccuhfffaoysan description electrophoresis method description endometrial effect description enzymatic effect description enzymatic reaction method description everyday effect description exhibiting effect description extraction method description extraction buffer substance description fluorescence detection method description | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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1710.06481 | 70 | pxgokwxkjxapgvuhfffaoysan fluorine chemical compound ff pxgokwxkjxapgvuhfffaoysan description wsfssnumvmoomruhfffaoysan formaldehyde chemical compound oc wsfssnumvmoomruhfffaoysan description formation reaction method description gene signature effect description general method method description glass substance description growth effect description human interleukin protein description imaging method method description immune response effect description immunoassay method description immunoblot method description immunological assay method description impacting effect description impotence disease description inhibitor substance description inhibitory effect effect description inosine drug description intercalation method description intestinal antibiotic drug description labelling method description leca protein description lectin substance description limiting effect description liquid substance description liquid suspension substance description lung cancer disease description magnesium sulfate inorganic material description csnnhwwhgaxbcpuhfffaoysal magnesium sulphate substance mgosooo csnnhwwhgaxbcpuhfffaoysal description magnesium sulphate nutrition description mammalian cell anatomy description mass spectrometry method description material substance description matrix material substance description mbha protein description mead nutrition description metal inorganic material description metal substance description microscopy method description microsphere substance description micturition effect description neoplastic effect description nitrocellulos polymer description nucleic acid protein description nucleotide group chemical group description occupational exposure toxicity description oligonucleotide synthesis method description ophthalmologic antibiotic drug description ovarian effect description physiological condition effect description point departure toxicity description polyphenylenevinylene polymer description polyacrylamide gel electrophoresis method description polyoxyethylene sorbitan monolaurate nutrition description polyvinylpyrrolidone polymer description polyvinylpyrrolidone substance description polyvinylpyrrolidone nutrition description processed protein peptide human gene description processed protein peptide protein description prognosis method description prokaryotic cell anatomy description proofreading effect description protective effect description quartz substance description quartz inorganic material description quenching method description renotropic effect description retained effect description ribonucleotide substance description ribonucleotide group chemical group description salt solution substance description sandwich elisa method description sarkosyl drug description secreting effect description silicon inorganic material description silicon substance description vypsynlajgmnejuhfffaoysan silicon dioxide inorganic material osio vypsynlajgmnejuhfffaoysan description sodium pyrophosphate drug description spoton substance description stabilization method description staining method description standard procedure method description starting material substance description stomach cancer disease description substance substance description substitution reaction method description supplementation effect description suppression effect description surgical procedure method description synthesis reaction method description synthesizing effect description temporal effect effect description tetrasodium diphosphate nutrition description tetrasodium phosphonato phosphate substance description therapeutic procedure method description transient effect description trisodium citrate drug description tumor biomarker substance description urethral stricture disease description urine analysis method description xlyofnoqvpjjnpuhfffaoysan water substance xlyofnoqvpjjnpuhfffaoysan description image classification cchemistry metallurgy cbiochemistry beer spirit wine vinegar microbiology enzymology mutation genetic engineering cqmeasuring testing process involving enzyme nucleic acid microorganism composition test paper therefor process preparing composition conditionresponsive control microbiological enzymological process cqmeasuring testing process involving enzyme nucleic acid microorganism composition therefor process preparing composition cqmeasuring testing process involving enzyme nucleic acid microorganism composition therefor process preparing composition involving nucleic acid cqnucleic acid product used analysis nucleic acid eg primer probe cqnucleic acid product used analysis nucleic acid eg primer probe disease caused alteration genetic material cqnucleic acid product used analysis nucleic acid eg primer probe disease caused alteration genetic material cancer gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material therefor cancer gnspecifically defined cancer gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gninvestigating analysing material specific method covered group gn gn gnbiological material eg blood urine haemocytometers gnchemical analysis biological material eg blood urine testing involving biospecific ligand binding method immunological testing gnimmunoassay biospecific binding assay material therefor gnimmunoassay biospecific binding assay material | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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1710.06481 | 71 | therefor cancer gnimmunoassay biospecific binding assay material therefor cancer involving compound serving marker tumor cancer neoplasia eg cellular determinant receptor heat shockstress protein aprotein oligosaccharide metabolite cchemistry metallurgy cbiochemistry beer spirit wine vinegar microbiology enzymology mutation genetic engineering cqmeasuring testing process involving enzyme nucleic acid microorganism composition test paper therefor process preparing composition conditionresponsive control microbiological enzymological process cqoligonucleotides characterized use cqprognosis disease development cchemistry metallurgy cbiochemistry beer spirit wine vinegar microbiology enzymology mutation genetic engineering cqmeasuring testing process involving enzyme nucleic acid microorganism composition test paper therefor process preparing composition conditionresponsive control microbiological enzymological process cqoligonucleotides characterized use cqexpression marker cchemistry metallurgy cbiochemistry beer spirit wine vinegar microbiology enzymology mutation genetic engineering cqmeasuring testing process involving enzyme nucleic acid microorganism composition test paper therefor process preparing composition conditionresponsive control microbiological enzymological process cqoligonucleotides characterized use cqprimer set multiplex assay gphysics gmeasuring testing gninvestigating analysing material determining chemical physical property gndetection diagnosis disease gncomplex way combining multiple protein biomarkers diagnosis abstract new method identifying patent hematuria low risk urothelial cancer uc include combining selected phenotypic variable level genotypic expression new metric gp index gp index combine age sex smoking history presence hematuria frequency hematuria genotypic expression genetic marker mdk cdc hoxa igfbp optionally ilrb determining gp index value obtained patient within one three group either high risk uc risk uc low risk uc group clinical laboratory work indicated patient group monitored periodically determine need clinical workup using gp index save substantial time effort fund avoiding unnecessary medical diagnostic procedure patient low risk uc description claim priority application continuation usc international patent application pctus filed nov claim priority u provisional patent application filed nov inventor david darling satish kumar mark dalphin paul osullivan application herein incorporated fully reference field invention invention relates detection patient disease specifically invention relates use genetic marker phenotypic marker triaging patient present hematuria without cancer particularly invention relates analysis genetic marker phenotypic marker triaging patient either macroscopic microscopic hematuria particularly invention relates use genetic phenotypic marker combination triage patient asymptomatic macroscopic microscopic hematuria predict whether patient condition warrant clinical procedure background survival cancer patient greatly enhanced cancer treated early case bladder cancer patient diagnosed disease confined primary site year survival rate compared patient metastatic disease altekruse et al therefore development lead early accurate diagnosis bladder cancer lead improved prognosis patient aid early detection cancer number cancer specific marker identified however use marker result false positive result patient inflammatory bladder disease bladder cancer asymptomatic hematuria ah one frequent urological finding incidence rate depending population schwartz g proper evaluation asymptomatic microscopic hematuria era evidencebased medicineprogress made mayo clin proc mcdonald swagerty wetzel l assessment microscopic hematuria adult afp grossfield g wolf j litwan hricak h shuler c agerter et al asymptomatic microscopic hematuria adult summary aua best practice policy recommendation afp ah however indicative broad range pathology urinary tract malignancy incidence ah population ranging full diagnostic work confirmed ah patient put considerable burden many healthcare system use phenotypic indicator segregate high low risk patient explored recent study loo et al loo r lieberman slezak j landa h mariani nicolaisen g aspera jaconsen stratifying risk urinary tract malignant tumor patient asymptomatic microscopic hematuria mayo clin proc abovementioned study patient presenting confirmed ah showed patient cause identified patient warranted form urological work identify cause approximately patient presenting ah diagnosed urothelial malignancy condition urinary tract infection uti kidney stone prostatic bleeding contamination making alternative diagnosis loo et al id summary identified new problem field namely identify patient presenting hematuria low risk bladder cancer solves problem many patient hematuria without bladder cancer may undergo expensive invasive workup workups needed thus invention useful exclude individual hazard cost associated full workup bladder cancer combination genetic information phenotypic information provides identification patient low risk bladder cancer effectively triage patient cancer cancerous condition including urothelial carcinoma transitional cell carcinoma tcc noncancerous condition including inflammatory | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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"id": "1710.06481"
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1710.06481 | 72 | disease invention represents new approach new problem unexpectedly useful diagnose cancer rather diagnose noncancers use combination genetic phenotypic criterion provide unexpectedly better discrimination either genetic phenotypic variable alone data obtained observation validated clia standard curtnorth shore product trial using bootstrap procedure internal validation phenotypic variable included presence smoking history hematuria gender age genetic variable included analysis expression igf hoxa mdk cdc ilr geneticphenotypic model gp performed unexpectedly better either genetic phenotypic variable alone macrohematuria finding visually identified blood urine common finding patient bladder cancer patient often standard practice perform additional diagnostic procedure diagnose bladder cancer however readily identifying patient microhematuria understanding implication microhematuria urothelial carcinoma remained problem herein provide improved method determining whether patient presenting either macrohematuria microhematuria could avoid invasive expensive clinical procedure detect urothelial carcinoma uc including bladder cancer patient sufficiently low probability bladder cancer warrant carrying additional procedure factor attributable high probability urothelial carcinoma uc described demographic factor gender race age addition environmental factor smoking history occupational exposure aromatic amine contribute significantly risk developing uc characterization patient healthcare assessment based factor used routinely adhoc basis example well accepted year old male smoking history presenting hematuria higher probability positive uc year old nonsmoking female presenting symptom however difference quantitated contribute overall probability patient uc attribution specific weight various genotypic phenotypic factor combining diagnostic test output add significantly accuracy diagnostic power noninvasive test provide clinician greater certainty segregating patient basis probability uc defined clinical biomarker test result although method available detect presence bladder cancer reliable accurate method determine whether patient low risk bladder cancer address need developed new analytical method distinguishing cancerous condition noncancerous one patient presenting hematuria either macrohematuria microhematuria aspect invention combine quantified phenotypic variable quantified expression genetic marker form combined segregation index gp index order effectively triage ah patient low probability uc ah patient high probability uc segregation defines dont need complete urological workup require complete workup thereby avoids unnecessary workups patient low probability uc phenotypic assay phenotypic variable evaluated gp index include frequency hematuria hfreq age gender smoking history red blood count rbc term defined herein phenotypic variable defined herein include clinical finding observation genotypic assay general preferred genotypic assay developed pacific edge ltd include quantification expression genetic marker cdc hoxa mdk igfbp marker assay another preferred assay marker fifth marker ilr quantified marker cxbladder assay trademark pacific edge ltd dunedin new zealand holyoake osullivan p pollock r et al development multiplex rna urine test detection stratification transitional cell carcinoma bladder clin cancer re osullivan p sharples k dalphin et al multigene urine test detection stratification bladder cancer patient presenting hematuria j urol vol international patent application pctnz entitled novel marker detection bladder cancer publication patent application herein incorporated fully reference separately incorporated preferred embodiment marker assay performed unfractionated urine using pcr amplification quantify four mrna marker cdc hoxa mdk igfbp overexpressed urothelial carcinoma ilr highly overexpressed neutrophil consequently elevated nonmalignant inflammatory condition inclusion th mrna marker significantly reduced risk false positive detection transitional cell carcinoma tcc patient perspective test noninvasive simple single sample urine often midstream urine exclusively taken often done home without coming clinic cxbladder assay shown considerably sensitive cytology patient presenting macroscopic hematuria notably cxbladder assay achieved sensitivity prespecified specificity urothelial carcinoma stage greater ta highgrade tumor cxbladder assay attribute single value score combine quantitative gene expression five gene represented patient urine score segregate patient three class based probability patient urothelial carcinoma patient presenting hematuria either macrohematuria microhematuria invention shown enhance genotypic tool either marker assay cxbladder assay addition phenotypic variable collected patient time period combine new tool index used segregate patient three defined risk class relative patient probability urothelial carcinoma uc aspect aspect | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
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1710.06481 | 73 | invention illustrated understood aspect embodiment invention person ordinary skill combine one aspect together produce additional aspect embodiment one aspect includes method determining patient presenting hematuria level risk urothelial cancer comprising providing sample urine said patient quantifying value mi comprising quantifying level expression human mdk cdc hoxa igfbp said sample assessing phenotypic variable hfreq agegt sex smk rbc said patient calculating gp index according either gp indexhfreqgendersmkmil orformula gp indexwhfreqwagegtwgenderwsmkwrbcwmwil gp index igf hoxa mdk cdc ilr sn hfreq gender age andformula ii determining whether gp index greater threshold indicating level risk patient urothelial cancer additional aspect include method aspect said threshold selected group gp index value said value indicates low risk indicates moderate risk indicates high risk aspect include method aspect said threshold gp index value said patient undergoes additional clinical laboratory test yet aspect include method prior aspect said threshold gp index value said patient undergoes additional clinical laboratory test still aspect include method aspect said threshold gp index value patient placed watch list clinical laboratory test additional aspect include method aspect threshold established using statistical method still aspect include method aspect wherein statistical method one linear discriminant analysis lda logistic regression logreg support vector machine svm knearest neighbor knn partition tree classifier tree additional aspect include method aspect comprising quantifying expression one additional genotypic marker selected fig fig aspect include method previous aspect said step quantifying genetic expression carried detecting level mrna aspect include method aspect wherein said step quantifying genetic expression carried detecting level cdna yet aspect include method aspect said step quantifying genetic expression carried using oligonucleotide complementary least portion said cdna additional aspect include method aspect said step quantifying genetic expression carried using qrtpcr method using forward primer reverse primer yet additional aspect include method aspect said step quantifying genetic expression carried detecting level protein still aspect include method aspect said step quantifying genetic expression carried detecting level peptide additional aspect include method aspect said step quantifying genetic expression carried using antibody directed said marker yet additional aspect include method claim said step quantifying genetic expression carried using sandwichtype immunoassay method using antibody chip still aspect include method aspect said quantifying genetic expression carried using monoclonal antibody aspect include method aspect said quantifying genetic expression carried using polyclonal antiserum gp index phenotypic genotypic variable described combined gp index according following relationship gp indexwhfreqwagegtwgenderwsmkwrbcwmwil hfreq mean frequency finding red blood cell per high power field month period frequency low hfreq higher red blood cell per high power field agegt refers subject age greater year agegt le year gender assigned value male female smk mean whether subject current exsmoker nonsmoker smk smoker rbc mean red blood cell count rbc set le mi combination expression genetic marker mdk cdc igfbp hoxa set le il refers expression level rna il il il set ness symbol mean multiplication operator weighting factor ww respectively weight assigned variable listed gp index preferred embodiment agegt rbc may dropped model shown gp indexhfreqgendersmkmil gp index produce value patient gp index value considered high risk bladder cancer indicates need additional work bladder cancer patient gp index value considered moderate risk developing bladder cancer additional work indicated patient gp index considered low risk developing bladder cancer patient low risk group placed watchful waiting list additional symptom appear recurrent episode | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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] | Transactions of the Association for Computational Linguistics
(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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"id": "1710.06481"
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1710.06481 | 74 | microhematuria occur reevaluated possible work described fully example fig found roc curve quantified phenotypic variable alone produced modest level diagnostic power roc curve quantified genotypic marker alone produced significant level diagnostic power found unexpectedly better diagnostic power genotypic phenotypic variable combined gp index quantification genetic expression protein nucleic acid secreted cleaved cell lost apoptotic mechanism either alone combination utility serum body fluid marker diagnosis disease including inflammatory disease bladder andor bladder cancer marker monitoring progression established disease detection protein cell marker carried using method known art include use rtpct qrtpcr monoclonal antibody polyclonal antiserum like specifically present invention provides method triaging patient presenting hematuria either macrohematuria microhematuria comprising providing biological sample ii detecting one bladder tumor marker btms said sample bladder tumor marker particular interest include mdk cdc hoxa igfbp marker assay optionally one also detect level human neutrophil marker interleukin receptor b ilrb sample cxbladder assay presence cancer established comparing level one btms level normal patient patient early stage bladder cancer andor patient inflammatory disease example presence cancer established comparing expression btms threshold expression threshold may order expression least time level expression group patient cancer aspect high expression ilrb without altered expression bladder tumor marker indicative inflammatory disease rather cancer method present invention used conjunction suitable marker detecting bladder cancer example suitable marker use invention outlined fig present invention includes use one marker outlined fig optionally preferred embodiment present invention include combination ilrb one marker mdk cdc hoxa igfbp also combination one marker suitable detecting bladder cancer example one marker outlined fig specifically present invention includes quantification expression one combination marker ilrbmdk ilrbcdc ilrbhoxa ilrbigfbp ilrbmdkcdc ilrbmdkhoxa ilrbmdkigfbp ilrbcdchoxa ilrbcdcigfbp ilrbhoxaigfbp ilrbmdkcdchoxa ilrbmdkcdcigfbp ilrbcdchoxaigfbp ilrbmdkcdchoxaigfbp combination optionally include one marker suitable detecting bladder cancer example one marker outlined fig present invention also provides method detecting inflammatory condition bladder comprising providing biological sample patient ii detecting level human neutrophil marker interleukin receptor b ilrb said sample presence inflammatory condition bladder established comparing level ilrb level normal patient patient hematuria patient inflammatory condition bladder example presence inflammatory condition bladder established comparing expression marker ilrb threshold threshold may order expression least time level expression another group patient preferred genotypic method present invention carried detecting suitable marker gene expression example determining level mrna cdna protein peptide utilizing suitable method establishment diagnosis established use classifier system example linear discriminant analysis lda logistic regression logreg support vector machine svm knearest neighbor knn partition tree classifier tree brief description figure invention described reference specific embodiment thereof reference figure fig fig figure fig b c depict protein mrna sequence ilrb also known cxcr fig af depict graph scatter plot showing effect ilrb separation tcc nonmalignant disease prostate disease cystitis urinary tract infection urolithiasis ilrb substituted different bladder cancer rna marker fig c f fig mdkigfbp fig b mdkhoxa fig c mdkilrb fig cdcigfbp fig e cdchoxa fig f cdcilrb fig ab depict roc curve analysis sensitivity v specificity showing effect including ilrb diagnostic algorithm derived using linear discriminate analysis ld linear regression lr roc curve derived patient tcc upper urinary tract cancer n nonmalignant disease cystitis urinary tract infection urolithiasis n fig ld solid ld dashed fig b lr solid lr dashed ilrb included ld lr fig b depict extended roc curve analysis showing effect including ilrb diagnostic algorithm derived using linear discriminate analysis ld linear regression lr roc curve derived patient tcc n unlike fig nonmalignant disease cohort n fig ld solid ld dashed | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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"id": "1710.06481"
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1710.06481 | 75 | fig b lr dashed lr solid ilrb included ld lr fig depicts box plot showing accumulation ilrb mrna urine patient nonmalignant urological disease rna quantified qrtpcr using deltact method holyoake et al method lower ct reflects higher rna level bph benign prostatic hyperplasia uti urinary tract infection n prostate nonspecific prostate disease vasc prostate vascular prostate warfarin hematuria secondary warfarin use observation patient cystitisuti significantly different p nonmalignant presentation shown fig ayy depict marker known expressed bladder cancer suitable use present invention fig ad depict marker known expressed bladder cancer suitable use present invention fig depicts flow chart patient recruitment procedure number example fig depicts baseline clinical demographic characteristic patient disease status month fig depicts overall sensitivity specificity urine test fig ab depict various roc curve fig depicts roc curve nmp elisa urnad test comprising four marker mdkcdcigfbphoxa fig b depicts roc curve five marker mdk cdc hoxa igfbp ilrb fig depicts sensitivity urine test stage grade location tumour multiplicity tumor hematuria status creatinine urine sample sex table show number percent positive urine test among tcc fig depicts specificity urine test diagnosis macrohematuria creatinine sex table show number negative urine test result among without tcc fig aiov depict roc curve combination marker fig aiav mdk fig bibv cdc fig cicv igfbp fig didv hoxa fig eiev mdkcdc fig fifv mdkigfbp fig gigv mdkhoxa fig hihv cdcigfbp fig iiiv cdchoxa fig jijv igfhoxa fig kikv mdkcdcigfbp fig lilv mdkcdchoxa fig mimv mdkigfbphoxa fig ninv cdcigfbphoxa fig oiov mdkcdcigfbphoxa plus minus ilrb using five different classifier model linear discriminant analysis lda ii logistic regression logreg iii support vector machine svm iv knearest neighbor knn v partition tree classifier tree fig ab depict result sensitivity selectivity study fig depicts area curve auc false positive rate specificity roc curve fig fig b show difference auc resulting inclusion ilrb fig ae depict graph sensitivity combination four marker mdk cdc igfbp hoxa plus minus ilrb using five different classifier model linear discriminant analysis lda ii logistic regression logreg iii support vector machine svm iv knearest neighbor knn v partition tree classifier tree different set specificity b c e fig aj depict gain sensitivity adding ilrb different set specificity fig fig b fig c fig fig e resulting gain specificity adding ilrb different set specificity fig f fig g fig h fig fig j fig depicts roc curve testing patient hematuria studied using either genetic testing alone phenotype evaluation alone andor genetic testing phenotypic evaluation fig depicts graph odds ratio horizontal axis variable gender smoking history hfreqnew invention fig b depict flow chart standard reporting diagnostic accuracy fig depicts flow chart patient macrohaematuria across three cohort study fig b depicts flow chart reporting diagnostic accuracy patient microhematuria included study fig depicts roc curve representing three classification model p index dotted line g index dashed line gp index solid line fig depicts npv versus proportion patient haematuria testing negative according model p index dotted line g index dashed line gp index solid line fig depicts graph relationship detect result horizontal axis versus triage result vertical axis fig depicts graph g index horizontal axis versus gp index vertical axis detailed description definition describing embodiment invention detail useful provide definition term used herein term marker refers molecule associated quantitatively qualitatively presence biological phenomenon example marker include polynucleotide gene gene fragment whether coding noncoding dna dna fragment rna rna fragment whether coding noncoding gene product including polypeptide peptide oligopeptide protein protein fragment related metabolite product identifying molecule antibody antibody fragment whether related directly indirectly mechanism underlying phenomenon marker invention include nucleotide sequence eg genbank sequence disclosed herein particular fulllength sequence coding sequence fragment possible probe eg created across exonexon boundary including capture motif hairpin fluorophores complement thereof measurable marker thereof defined used herein antibody like term refer immunoglobulin molecule immunologically active portion immunoglobulin ig molecule ie molecule contain antigen binding site specifically bind immunoreacts antigen include limited polyclonal monoclonal chimeric single chain fc fab fab fab fragment fab expression library antibody molecule relate class igg igm iga ige igd differ one another nature heavy chain present molecule include subclass well igg igg others light | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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"id": "1710.06481"
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1710.06481 | 76 | chain may kappa chain lambda chain reference herein antibody includes reference class subclass type also included chimeric antibody example monoclonal antibody fragment thereof specific one source eg mouse human sequence included camelid antibody shark antibody nanobodies term cancer cancerous refer describe physiological condition mammal typically characterized abnormal unregulated cell growth cancer cancer pathology associated example metastasis interference normal functioning neighboring cell release cytokine secretory product abnormal level suppression aggravation inflammatory immunological response neoplasia premalignancy malignancy invasion surrounding distant tissue organ lymph node etc term tumor refers neoplastic cell growth proliferation whether malignant benign precancerous cancerous cell tissue term bladder cancer refers tumor originating bladder tumor able metastasize organ term btm bladder tumor marker btm family member mean tumor marker associated urothelial cancer bladder cancer transitional cell carcinoma bladder tcc squamous cell carcinoma adenocarcinoma bladder term btm also includes combination individual marker whose combination improves sensitivity specificity detecting bladder cancer understood term btm require marker specific bladder tumor rather expression btm altered type cell diseased cell tumor including malignant tumor term expressing btm mean marker show lower expression bladder tumor nonmalignant bladder tissue term expressing btm mean marker show higher expression bladder tumor nonmalignant tissue term differentially expressed differential expression like phrase refer gene marker whose expression activated higher lower level subject eg test sample condition specifically cancer melanoma relative expression control subject eg reference sample term also include marker whose expression activated higher lower level different stage condition disease good poor prognosis cell higher lower level proliferation differentially expressed marker may either activated inhibited polynucleotide level polypeptide level may subject alternative splicing result different polypeptide product difference may evidenced change mrna level surface expression secretion partitioning polypeptide example differential expression may include comparison expression two marker eg gene gene product comparison ratio expression two marker eg gene gene product comparison two differently processed product eg transcript polypeptide marker differ normal subject diseased subject various stage disease disease good poor prognosis cell higher lower level proliferation normal tissue diseased tissue specifically cancer melanoma differential expression includes quantitative well qualitative difference temporal cellular expression pattern gene expression product among example normal diseased cell among cell undergone different disease event disease stage cell different level proliferation term expression includes production polynucleotides polypeptide particular production rna eg mrna gene portion gene includes production polypeptide encoded rna gene portion gene appearance detectable material associated expression example formation complex example polypeptidepolypeptide interaction polypeptidenucleotide interaction like included within scope term expression another example binding binding ligand hybridization probe antibody gene polynucleotide oligonucleotide polypeptide protein fragment visualization binding ligand thus intensity spot microarray hybridization blot northern blot immunoblot western blot bead array pcr analysis included within term expression underlying biological molecule term gene expression threshold defined expression threshold used interchangeably refer level marker question outside expression level polynucleotide polypeptide serf predictive marker condition patient example expression ilrb certain threshold diagnostic patient inflammatory condition threshold also used testing patient suspected bladder cancer using bladder cancer maker expression level threshold indicates patient inflammatory bladder condition likely cause false positive test cancer whereas expression level ilrb threshold predictive patient inflammatory bladder condition including measurement ilrb result expression bladder tumor marker relied upon level ilrb threshold ie positive result likely positive patient cancer rather increased level bladder tumor marker actually resulting exfoliation nonmalignant cell mucosa inflammation term diagnostic threshold refers threshold patient said diagnosed either without given condition example bladder cancer diagnostic threshold generally set achieve desired | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
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"id": "1710.06481"
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1710.06481 | 77 | sensitivity specificity depending factor population prevalence likely clinical outcome general diagnostic threshold calculated andor established using algorithm andor computerized data analysis exact threshold dependent population also model used predict disease predictive model threshold established experimentally clinical study described example depending prediction model used expression threshold may set achieve maximum sensitivity maximum specificity minimum error maximum classification rate example higher threshold may set achieve minimum error may result lower sensitivity therefore given predictive model clinical study used set expression threshold generally achieves highest sensitivity minimal error rate term sensitivity mean proportion individual disease test model positive thus increased sensitivity mean fewer false negative test result term specificity mean proportion individual without disease test model negative thus increased specificity mean fewer false positive test result term receiver operating characteristic roc curve mean plot true positive rate sensitivity false positive rate specificity different cut point particular marker test point roc curve represents specific sensitivityspecificity point correspond given threshold roc curve important establish threshold give desired outcome area roc curve represents expressed area curve auc analysis measure well given marker test consisting number marker distinguish two diagnostic outcome roc curve also used compare accuracy two different test term oligonucleotide refers polynucleotide typically probe primer including without limitation singlestranded deoxyribonucleotides single doublestranded ribonucleotides rna dna hybrid doublestranded dna oligonucleotides singlestranded dna probe oligonucleotides often synthesized chemical method example using automated oligonucleotide synthesizer commercially available variety method including vitro expression system recombinant technique expression cell organism term overexpression overexpressed refers expression level gene marker patient seen normal tissue expression may considered overexpressed time expression normal tissue tissue another group patient term polynucleotide used singular plural generally refers polyribonucleotide polydeoxribonucleotide may unmodified rna dna modified rna dna includes without limitation single doublestranded dna dna including single doublestranded region single doublestranded rna rna including single doublestranded region hybrid molecule comprising dna rna may singlestranded typically doublestranded include single doublestranded region also included triplestranded region comprising rna dna rna dna specifically included mrna cdna genomic dna fragment thereof term includes dna rna contain one modified base tritiated base unusual base inosine polynucleotides invention encompass coding noncoding sequence sense antisense sequence understood reference polynucleotide like term herein include fulllength sequence well fragment derivative variant thereof term phenotypic mean trait observable clinical setting clinical interview patient history used formula calculating gp index phenotypic p mean patient age sex incidence hematuria smoking history polypeptide used herein refers oligopeptide peptide protein sequence fragment thereof naturally occurring recombinant synthetic semisynthetic molecule polypeptide recited herein refer amino acid sequence naturally occurring protein molecule polypeptide like term meant limit amino acid sequence complete native amino acid sequence fulllength molecule understood reference polypeptide like term herein include fulllength sequence well fragment derivative variant thereof term qpcr qpcr refers quantitative polymerase chain reaction described example pcr technique quantitative pcr j w larrick ed eaton publishing az quantitative pcr bustin ed iul press term reverse transcription mean process oligoribonucleotide including messenger rna mrna used template biochemical synthesis complementary oligodeoxyribonucleotide cdna using enzyme reverse transcriptase bind template rna catalyzes series addition reaction sequentially attache deoxyribonucleotide base form oligodeoxyribonucleotide strand complementary rna template term hematuria defined presence blood urine may present macroscopic hematura visible trace blood cell microscopic hematuria microscopic trace blood within urine confirmed indication microhematuria defined red blood cell present per microscopic highpowered field hpf minimum properly collected urine sample microhematuria may also detected urine dipstick colorimetric comparison estimate clinic hematuria either microscopic macroscopic may asymptomatic additional symptom associated hematuria symptomatic additional symptom include dysuria painful urination feeling incomplete emptying bladder increased frequency urination stringency hybridization reaction readily determinable one ordinary skill art generally empirical calculation dependent upon probe length washing temperature salt | 1710.06481 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1710.06481 | [
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(TACL), Vol 6 (2018), pages 287-302 | cs.CL | 20171017 | 20180611 | [
{
"id": "1710.06481"
}
] | ||
1707.06347 | 0 | concentration general longer probe require higher temperature proper annealing shorter probe need lower temperature hybridization generally depends ability denatured dna reanneal complementary strand present environment melting temperature higher degree desired homology probe hybridizable sequence higher relative temperature used result follows higher relative temperature would tend make reaction condition stringent lower temperature le additional detail explanation stringency hybridization reaction found eg ausubel et al current protocol molecular biology wiley interscience publisher stringent condition high stringency condition defined herein typically employ low ionic strength high temperature washing example sodium chloride sodium citrate sodium dodecyl sulfate c employ denaturing agent hybridization formamide example vv formamide bovine serum albumin fico polyvinylpyrrolidone mm sodium phosphate buffer ph mm sodium chloride mm sodium citrate c employ formamide ssc nacl sodium citrate mm sodium phosphate ph sodium pyrophosphate denhardts solution sonicated salmon sperm dna ugml sd dextran sulfate c wash c ssc sodium chloridesodium citrate formamide c followed highstringency wash comprising ssc containing edta c moderately stringent condition may identified described sambrook et al molecular cloning laboratory manual new york cold spring harbor press include use washing solution hybridization condition e g temperature ionic strength sd le stringent described example moderately stringent condition overnight incubation c solution comprising formamide ssc mm nacl mm trisodium citrate mm sodium phosphate ph denhardts solution dextran sulfate mgml denatured sheared salmon sperm dna followed washing filter ssc c skilled artisan recognize adjust temperature ionic strength etc necessary accommodate factor probe length like term ilrb mean neutrophil marker interleukin receptor b also known chemokine cxc motif receptor cxcr fig seq id no includes marker ilrb term includes polynucleotide gene gene fragment rna rna fragment gene product including polypeptide peptide oligopeptide protein protein fragment related metabolite product identifying molecule antibody antibody fragment term reliability includes low incidence false positive andor false negative thus higher reliability marker fewer false positive andor false negative associated diagnosis made using marker accuracy proportion true result true positive plus true negative divided number total case population according formula true positive true negative total number measurement term triage mean differentiate patient hematuria low probability bladder cancer patient hematuria reasonable probability bladder cancer requiring clinical work including cystoscopy clinical procedure embodiment therefore certain preferred embodiment combination genetic marker phenotypic marker provided permit differentiating patient low probability bladder cancer patient sufficient risk bladder warrant clinical work possibly including cystoscopy procedure embodiment marker provided reliability greater embodiment greater still embodiment greater yet embodiment greater still others greater yet embodiment greater certain embodiment reliability genetic analysis practice present invention employ unless otherwise indicated conventional technique molecular biology including recombinant technique microbiology cell biology biochemistry within skill art technique explained fully literature molecular cloning laboratory manual nd edition sambrook et al oligonucleotide synthesis j gait ed animal cell culture r freshney ed method enzymology academic press inc handbook experimental immunology th edition weir cc blackwell ed blackwell science inc gene transfer vector mammalian cell j miller p calos ed current protocol molecular biology f ausubel et al ed pcr polymerase chain reaction mullis et al ed understood term may refer protein dna sequence andor rna sequence also understood term also refer nonhuman protein dna andor rna homologous sequence depicted herein embodiment invention often patient referred urologist hematuria booked seen dedicated hematuria clinic patient macroscopic hematuria often prioritized micro hematuria information provided time referral primary care provider highly variable making accurate stratification patient probability urothelial cancer difficult often urine cytology routinely requested patient seen positive used increase patient priority receiving full clinical workup however urine cytology whilst highly specific low sensitivity hence little practical value high rate falsenegatives phenotypic genotypic analysis patient hematuria bladder cancer gp index phenotypic | 1707.06347 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1707.06347 | [
"cs.LG"
] | null | cs.LG | 20170720 | 20170828 | [
{
"id": "1604.06778"
},
{
"id": "1506.02438"
},
{
"id": "1602.01783"
},
{
"id": "1611.01224"
},
{
"id": "1707.06347"
},
{
"id": "1707.02286"
},
{
"id": "1606.01540"
}
] | ||
1707.06347 | 1 | genotypic variable described combined gp index according following relationship gp indexwhfreqwagegtwgenderwsmkwrbcwmwil hfreq mean frequency finding red blood cell per high power field month period frequency low hfreq higher red blood cell per high power field agegt refers subject age greater year agegt le year gender assigned value male female smk mean whether subject current exsmoker nonsmoker smk smoker rbc mean red blood cell count rbc set le mi combination expression genetic marker mdk cdc igfbp hoxa set le il refers expression level rna il il il set ness symbol mean multiplication operator weighting factor ww respectively weight assigned variable listed gp index preferred embodiment agegt rbc may dropped model shown gp indexhfreqgendersmkmil gp index produce value patient gp index value considered high risk bladder cancer indicates need additional work bladder cancer patient gp index value considered moderate risk developing bladder cancer additional work indicated patient gp index considered low risk developing bladder cancer patient low risk group placed watchful waiting list additional symptom appear recurrent episode microhematuria occur reevaluated possible work genotypic variable useful differentiating patient without bladder cancer include expression rna marker combination mdk cdc igfbp igbp hoxa another genotypic variable expression rna ilr coefficient genotypic variable shown table threshold used ilr respectively coefficient respectively assigned gp index produce value gp index value considered high risk bladder cancer indicates need additional work bladder cancer gp index value considered moderate risk developing bladder cancer additional work indicated gp index considered low risk developing bladder cancer patient placed waiting list additional symptom appear recurrent episode microhematuria occur reevaluated possible fuller work described fully example fig found roc curve phenotypic data alone produced modest level diagnostic power roc curve genotypic data alone produced significant level diagnostic power found unexpectedly better diagnostic power genotypic phenotypic data combined gp index genetic analysis patient bladder cancer preferred embodiment invention combine use marker assay cxbladder assay genotypic variable one five key risk factor phenotypic variable produce selection index used triage patient microscopic macroscopic hematuria term potential risk urothelial cancer precluding need flexible cystoscopy patient deemed high risk urothelial cancer based phenotypic variable genotypic variable may seen earlier potentially improving overall patient outcome genotypic marker used tool detect cancerfree patient select patient group low medium high risk disease marker example differentially expressed disease tissue corresponding nondisease tissue situation detection differential expression associated presence disease alternatively marker associated directly change occurring disease tissue change resulting disease inflammatory disease associated increase neutrophil found neutrophil marker interleukin receptor b ilrb fig seq id no provide good marker presence neutrophil sample therefore used diagnostic marker detection inflammatory disease sample particular detection inflammatory disease bladder shown fig accumulation ilrb urine indicative presence inflammatory disease bladder specifically fig show accumulation ilrb urine patient condition benign prostatic hyperplasia urinary tract infection nonspecific prostate disease vascular prostate secondary warfarin use appreciated however use ilrb limited detection disease example show ilrb increase sample patient inflammatory disease bladder ilrb used marker inflammation associated bladder disease therefore suitable use detecting condition associated inflammation therefore detection amount ilrb used marker inflammatory disease bladder particularly ilrb used detect inflammatory disease bladder associated accumulation neutrophil urine test tcc rely largely | 1707.06347 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1707.06347 | [
"cs.LG"
] | null | cs.LG | 20170720 | 20170828 | [
{
"id": "1604.06778"
},
{
"id": "1506.02438"
},
{
"id": "1602.01783"
},
{
"id": "1611.01224"
},
{
"id": "1707.06347"
},
{
"id": "1707.02286"
},
{
"id": "1606.01540"
}
] | ||
1707.06347 | 2 | presence marker urine derived exfoliated tumor cell ability detect cell masked presence large number contaminating cell blood inflammatory cell moreover inflammation bladder lining result increased exfoliation nonmalignant cell mucosa result urine test use marker derived bladder transitional cell higher likelihood giving false positive result urine sample taken patient cystitis urinary tract infection condition resulting urinary tract inflammation transitional cell exfoliation urolithiasis sanchezcarbayo et al one way try avoid false positive result select marker low relative expression blood inflammatory cell use marker result fewer false positive tcc patient presenting nonmalignant inflammatory condition however low expression marker hematologicallyderived cell fails compensate enhanced rate exfoliation nonmalignant transitional cell discovered negative impact exfoliated transitional cell inflamed tissue accuracy bladder cancer urine test minimized improving identification patient inflammatory condition urinary tract surprisingly found using marker ilrb combination one bladder tumor marker btms provides accurate detection bladder cancer particular marker based test bladder cancer includes marker ilrb le susceptible false positive result result patient suffering inflammatory noncancer condition general presence absence inflammatory condition established threshold gene expression expression ilrb indicative inflammatory condition example expression ilrb certain threshold diagnostic patient inflammatory condition see threshold described ilrb used conjunction one marker predictive presence bladder cancer presence elevated expression bladder tumor marker expression ilrb certain threshold predictive patient inflammatory condition cancer furthermore test preformed urine patient result predictive patient inflammatory bladder condition high level bladder tumor marker likely result nonmalignant cell coming mucosa result inflammation patient although high level bladder tumor marker actually bladder cancera false positive alternatively patient abnormally high level diagnostic level one bladder tumor marker level ilrb threshold patient likely cancer particular bladder urothelial cancer especially test preformed urine patient result significant benefit health provider sure patient cancer start treatment immediately concerned result actually caused inflammatory condition giving false positive result surprisingly shown quantification rna gene encoding neutrophil marker interleukin receptor b ilrb improves overall performance detecting patient tcc using known tcc btm marker reference sequence ilrb shown fig seq id no addition role tcc detection explored whether ilrb could used urine marker aid diagnosis inflammatory disease fig use ilrb marker used isolation detection inflammatory condition bladder utilizing known method detecting gene expression level example method detecting gene expression outlined alternatively ilrb combined one btms detect bladder cancer shown utilizing inflammatory disease marker ilrb part test bladder cancer influence inflamed tissue creating false positive result minimized marker ilrb used association bladder cancer marker alternatively used two marker part signature detecting bladder cancer reducing number false positive result mean fewer patient bladder cancer subjected potentially unnecessary procedure including cystoscopy carry risk reducing number false negative result mean likely patient bladder cancer detected therefore evaluated cancer action ilrb improve detection bladder cancer result ability separate nonmalignant condition patient bladder cancer achieved increase ilrb indicative increase presence neutrophil sample therefore ability ilrb dependent bladder tumor marker used shown fig combined variety bladder tumor marker combination bladder tumor marker ilrb general effect increasing specificity ability marker detect cancer subject one example signature according present invention use ilrb combination mdk cdc igfbp hoxa may also combination one marker suitable detecting bladder cancer example one marker outlined fig shown fig ilrb used combination marker specifically combination ilrbmdk ilrbcdc ilrbhoxa ilrbigfbp ilrbmdkcdc ilrbmdkhoxa ilrbmdkigfbp ilrbcdchoxa ilrbcdcigfbp ilrbhoxaigfbp ilrbmdkcdchoxa ilrbmdkcdcigfbp ilrbcdchoxaigfbp ilrbmdkcdchoxaigfbp shown fig | 1707.06347 | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | method detecting genetic phenotypic biomarkers urothelial carcinoma treatment thereof | http://arxiv.org/pdf/1707.06347 | [
"cs.LG"
] | null | cs.LG | 20170720 | 20170828 | [
{
"id": "1604.06778"
},
{
"id": "1506.02438"
},
{
"id": "1602.01783"
},
{
"id": "1611.01224"
},
{
"id": "1707.06347"
},
{
"id": "1707.02286"
},
{
"id": "1606.01540"
}
] |
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