diff --git "a/test_predictions.txt" "b/test_predictions.txt"
new file mode 100644--- /dev/null
+++ "b/test_predictions.txt"
@@ -0,0 +1,25439 @@
+Clustering O
+of O
+missense O
+mutations O
+in O
+the O
+ataxia B
+- I
+telangiectasia I
+gene O
+in O
+a O
+sporadic B
+T I
+- I
+cell I
+leukaemia I
+. O
+
+Ataxia B
+- I
+telangiectasia I
+( O
+A B
+- I
+T I
+) O
+is O
+a O
+recessive B
+multi I
+- I
+system I
+disorder I
+caused O
+by O
+mutations O
+in O
+the O
+ATM O
+gene O
+at O
+11q22 O
+- O
+q23 O
+( O
+ref O
+. O
+3 O
+) O
+. O
+
+The O
+risk O
+of O
+cancer B
+, O
+especially O
+lymphoid B
+neoplasias I
+, O
+is O
+substantially O
+elevated O
+in O
+A B
+- I
+T I
+patients O
+and O
+has O
+long O
+been O
+associated O
+with O
+chromosomal O
+instability O
+. O
+
+By O
+analysing O
+tumour B
+DNA O
+from O
+patients O
+with O
+sporadic O
+T I
+- I
+cell I
+prolymphocytic I
+leukaemia I
+( O
+T B
+- I
+PLL I
+) O
+, O
+a O
+rare O
+clonal B
+malignancy I
+with O
+similarities O
+to O
+a O
+mature B
+T I
+- I
+cell I
+leukaemia I
+seen O
+in O
+A B
+- I
+T I
+, O
+we O
+demonstrate O
+a O
+high O
+frequency O
+of O
+ATM O
+mutations O
+in O
+T B
+- I
+PLL I
+. O
+
+In O
+marked O
+contrast O
+to O
+the O
+ATM O
+mutation O
+pattern O
+in O
+A B
+- I
+T I
+, O
+the O
+most O
+frequent O
+nucleotide O
+changes O
+in O
+this O
+leukaemia B
+were O
+missense O
+mutations O
+. O
+
+These O
+clustered O
+in O
+the O
+region O
+corresponding O
+to O
+the O
+kinase O
+domain O
+, O
+which O
+is O
+highly O
+conserved O
+in O
+ATM O
+- O
+related O
+proteins O
+in O
+mouse O
+, O
+yeast O
+and O
+Drosophila O
+. O
+
+The O
+resulting O
+amino O
+- O
+acid O
+substitutions O
+are O
+predicted O
+to O
+interfere O
+with O
+ATP O
+binding O
+or O
+substrate O
+recognition O
+. O
+
+Two O
+of O
+seventeen O
+mutated O
+T O
+- O
+PLL O
+samples O
+had O
+a O
+previously O
+reported O
+A B
+- I
+T I
+allele O
+. O
+
+In O
+contrast O
+, O
+no O
+mutations O
+were O
+detected O
+in O
+the O
+p53 O
+gene O
+, O
+suggesting O
+that O
+this O
+tumour B
+suppressor O
+is O
+not O
+frequently O
+altered O
+in O
+this O
+leukaemia B
+. O
+
+Occasional O
+missense O
+mutations O
+in O
+ATM O
+were O
+also O
+found O
+in O
+tumour B
+DNA O
+from O
+patients O
+with O
+B B
+- I
+cell I
+non I
+- I
+Hodgkins I
+lymphomas I
+( O
+B B
+- I
+NHL I
+) O
+and O
+a O
+B O
+- O
+NHL O
+cell O
+line O
+. O
+
+The O
+evidence O
+of O
+a O
+significant O
+proportion O
+of O
+loss O
+- O
+of O
+- O
+function O
+mutations O
+and O
+a O
+complete O
+absence O
+of O
+the O
+normal O
+copy O
+of O
+ATM O
+in O
+the O
+majority O
+of O
+mutated O
+tumours B
+establishes O
+somatic O
+inactivation O
+of O
+this O
+gene O
+in O
+the O
+pathogenesis O
+of O
+sporadic O
+T B
+- I
+PLL I
+and O
+suggests O
+that O
+ATM O
+acts O
+as O
+a O
+tumour B
+suppressor O
+. O
+
+As O
+constitutional O
+DNA O
+was O
+not O
+available O
+, O
+a O
+putative O
+hereditary O
+predisposition O
+to O
+T B
+- I
+PLL I
+will O
+require O
+further O
+investigation O
+. O
+. O
+
+Myotonic B
+dystrophy I
+protein O
+kinase O
+is O
+involved O
+in O
+the O
+modulation O
+of O
+the O
+Ca2 O
++ O
+homeostasis O
+in O
+skeletal O
+muscle O
+cells O
+. O
+
+Myotonic B
+dystrophy I
+( O
+DM B
+) O
+, O
+the O
+most O
+prevalent O
+muscular B
+disorder I
+in O
+adults O
+, O
+is O
+caused O
+by O
+( O
+CTG O
+) O
+n O
+- O
+repeat O
+expansion O
+in O
+a O
+gene O
+encoding O
+a O
+protein O
+kinase O
+( O
+DM B
+protein O
+kinase O
+; O
+DMPK O
+) O
+and O
+involves O
+changes O
+in O
+cytoarchitecture O
+and O
+ion O
+homeostasis O
+. O
+
+To O
+obtain O
+clues O
+to O
+the O
+normal O
+biological O
+role O
+of O
+DMPK O
+in O
+cellular O
+ion O
+homeostasis O
+, O
+we O
+have O
+compared O
+the O
+resting O
+[ O
+Ca2 O
++ O
+] O
+i O
+, O
+the O
+amplitude O
+and O
+shape O
+of O
+depolarization O
+- O
+induced O
+Ca2 O
++ O
+transients O
+, O
+and O
+the O
+content O
+of O
+ATP O
+- O
+driven O
+ion O
+pumps O
+in O
+cultured O
+skeletal O
+muscle O
+cells O
+of O
+wild O
+- O
+type O
+and O
+DMPK O
+[ O
+- O
+/ O
+- O
+] O
+knockout O
+mice O
+. O
+
+In O
+vitro O
+- O
+differentiated O
+DMPK O
+[ O
+- O
+/ O
+- O
+] O
+myotubes O
+exhibit O
+a O
+higher O
+resting O
+[ O
+Ca2 O
++ O
+] O
+i O
+than O
+do O
+wild O
+- O
+type O
+myotubes O
+because O
+of O
+an O
+altered O
+open O
+probability O
+of O
+voltage O
+- O
+dependent O
+l O
+- O
+type O
+Ca2 O
++ O
+and O
+Na O
++ O
+channels O
+. O
+
+The O
+mutant O
+myotubes O
+exhibit O
+smaller O
+and O
+slower O
+Ca2 O
++ O
+responses O
+upon O
+triggering O
+by O
+acetylcholine O
+or O
+high O
+external O
+K O
++ O
+. O
+
+In O
+addition O
+, O
+we O
+observed O
+that O
+these O
+Ca2 O
++ O
+transients O
+partially O
+result O
+from O
+an O
+influx O
+of O
+extracellular O
+Ca2 O
++ O
+through O
+the O
+l O
+- O
+type O
+Ca2 O
++ O
+channel O
+. O
+
+Neither O
+the O
+content O
+nor O
+the O
+activity O
+of O
+Na O
++ O
+/ O
+K O
++ O
+ATPase O
+and O
+sarcoplasmic O
+reticulum O
+Ca2 O
++ O
+- O
+ATPase O
+are O
+affected O
+by O
+DMPK O
+absence O
+. O
+
+In O
+conclusion O
+, O
+our O
+data O
+suggest O
+that O
+DMPK O
+is O
+involved O
+in O
+modulating O
+the O
+initial O
+events O
+of O
+excitation O
+- O
+contraction O
+coupling O
+in O
+skeletal O
+muscle O
+. O
+. O
+
+Constitutional O
+RB1 O
+- O
+gene O
+mutations O
+in O
+patients O
+with O
+isolated B
+unilateral I
+retinoblastoma I
+. O
+
+In O
+most O
+patients O
+with O
+isolated B
+unilateral I
+retinoblastoma I
+, O
+tumor B
+development O
+is O
+initiated O
+by O
+somatic O
+inactivation O
+of O
+both O
+alleles O
+of O
+the O
+RB1 O
+gene O
+. O
+
+However O
+, O
+some O
+of O
+these O
+patients O
+can O
+transmit O
+retinoblastoma B
+predisposition O
+to O
+their O
+offspring O
+. O
+
+To O
+determine O
+the O
+frequency O
+and O
+nature O
+of O
+constitutional O
+RB1 O
+- O
+gene O
+mutations O
+in O
+patients O
+with O
+isolated B
+unilateral I
+retinoblastoma I
+, O
+we O
+analyzed O
+DNA O
+from O
+peripheral O
+blood O
+and O
+from O
+tumor B
+tissue O
+. O
+
+The O
+analysis O
+of O
+tumors B
+from O
+54 O
+( O
+71 O
+% O
+) O
+of O
+76 O
+informative O
+patients O
+showed O
+loss O
+of O
+constitutional O
+heterozygosity O
+( O
+LOH O
+) O
+at O
+intragenic O
+loci O
+. O
+
+Three O
+of O
+13 O
+uninformative O
+patients O
+had O
+constitutional O
+deletions O
+. O
+
+For O
+39 O
+randomly O
+selected O
+tumors B
+, O
+SSCP O
+, O
+hetero O
+- O
+duplex O
+analysis O
+, O
+sequencing O
+, O
+and O
+Southern O
+blot O
+analysis O
+were O
+used O
+to O
+identify O
+mutations O
+. O
+
+Mutations O
+were O
+detected O
+in O
+21 O
+( O
+91 O
+% O
+) O
+of O
+23 O
+tumors B
+with O
+LOH B
+. O
+
+In O
+6 O
+( O
+38 O
+% O
+) O
+of O
+16 O
+tumors B
+without O
+LOH O
+, O
+one O
+mutation O
+was O
+detected O
+, O
+and O
+in O
+9 O
+( O
+56 O
+% O
+) O
+of O
+the O
+tumors B
+without O
+LOH O
+, O
+both O
+mutations O
+were O
+found O
+. O
+
+Thus O
+, O
+a O
+total O
+of O
+45 O
+mutations O
+were O
+identified O
+in O
+tumors B
+of O
+36 O
+patients O
+. O
+
+Thirty O
+- O
+nine O
+of O
+the O
+mutations O
+- O
+including O
+34 O
+small O
+mutations O
+, O
+2 O
+large O
+structural O
+alterations O
+, O
+and O
+hypermethylation O
+in O
+3 O
+tumors B
+- O
+were O
+not O
+detected O
+in O
+the O
+corresponding O
+peripheral O
+blood O
+DNA O
+. O
+
+In O
+6 O
+( O
+17 O
+% O
+) O
+of O
+the O
+36 O
+patients O
+, O
+a O
+mutation O
+was O
+detected O
+in O
+constitutional O
+DNA O
+, O
+and O
+1 O
+of O
+these O
+mutations O
+is O
+known O
+to O
+be O
+associated O
+with O
+reduced O
+expressivity O
+. O
+
+The O
+presence O
+of O
+a O
+constitutional O
+mutation O
+was O
+not O
+associated O
+with O
+an O
+early O
+age O
+at O
+treatment O
+. O
+
+In O
+1 O
+patient O
+, O
+somatic O
+mosaicism O
+was O
+demonstrated O
+by O
+molecular O
+analysis O
+of O
+DNA O
+and O
+RNA O
+from O
+peripheral O
+blood O
+. O
+
+In O
+2 O
+patients O
+without O
+a O
+detectable O
+mutation O
+in O
+peripheral O
+blood O
+, O
+mosaicism O
+was O
+suggested O
+because O
+1 O
+of O
+the O
+patients O
+showed O
+multifocal B
+tumors I
+and O
+the O
+other O
+later O
+developed O
+bilateral B
+retinoblastoma I
+. O
+
+In O
+conclusion O
+, O
+our O
+results O
+emphasize O
+that O
+the O
+manifestation O
+and O
+transmissibility O
+of O
+retinoblastoma B
+depend O
+on O
+the O
+nature O
+of O
+the O
+first O
+mutation O
+, O
+its O
+time O
+in O
+development O
+, O
+and O
+the O
+number O
+and O
+types O
+of O
+cells O
+that O
+are O
+affected O
+. O
+. O
+
+Hereditary B
+deficiency I
+of I
+the I
+fifth I
+component I
+of I
+complement I
+in O
+man O
+. O
+
+I O
+. O
+
+Clinical O
+, O
+immunochemical O
+, O
+and O
+family O
+studies O
+. O
+
+The O
+first O
+recognized O
+human O
+kindred O
+with O
+hereditary B
+deficiency I
+of I
+the I
+fifth I
+component I
+of I
+complement I
+( O
+C5 O
+) O
+is O
+described O
+. O
+
+The O
+proband O
+, O
+a O
+20 O
+- O
+year O
+- O
+old O
+black O
+female O
+with O
+systemic B
+lupus I
+erythematosus I
+since O
+age O
+11 O
+, O
+lacked O
+serum O
+hemolytic O
+complement O
+activity O
+, O
+even O
+during O
+remission O
+. O
+
+C5 O
+was O
+undetectable O
+in O
+her O
+serum O
+by O
+both O
+immunodiffusion O
+and O
+hemolytic O
+assays O
+. O
+
+Other O
+complement O
+components O
+were O
+normal O
+during O
+remission O
+of O
+lupus B
+, O
+but O
+C1 O
+, O
+C4 O
+, O
+C2 O
+, O
+and O
+C3 O
+levels O
+fell O
+during O
+exacerbations O
+. O
+
+A O
+younger O
+half O
+- O
+sister O
+, O
+who O
+had O
+no O
+underlying O
+disease O
+, O
+was O
+also O
+found O
+to O
+lack O
+immunochemically O
+detectable O
+C5 O
+. O
+
+By O
+hemolytic O
+assay O
+, O
+she O
+exhibited O
+1 O
+- O
+2 O
+% O
+of O
+the O
+normal O
+serum O
+C5 O
+level O
+and O
+normal O
+concentrations O
+of O
+other O
+complement O
+components O
+. O
+
+C5 O
+levels O
+of O
+other O
+family O
+members O
+were O
+either O
+normal O
+or O
+approximately O
+half O
+- O
+normal O
+, O
+consistent O
+with O
+autosomal O
+codominant O
+inheritance O
+of O
+the O
+gene O
+determining O
+C5 B
+deficiency I
+. O
+
+Normal O
+hemolytic O
+titers O
+were O
+restored O
+to O
+both O
+homozygous O
+C5 B
+- I
+deficient I
+( O
+C5D B
+) O
+sera O
+by O
+addition O
+of O
+highly O
+purified O
+human O
+C5 O
+. O
+
+In O
+specific O
+C5 O
+titrations O
+, O
+however O
+, O
+it O
+was O
+noted O
+that O
+when O
+limited O
+amounts O
+of O
+C5 O
+were O
+assayed O
+in O
+the O
+presence O
+of O
+low O
+dilutions O
+of O
+either O
+C5D B
+serum O
+, O
+curving O
+rather O
+than O
+linear O
+dose O
+- O
+response O
+plots O
+were O
+consistently O
+obtained O
+, O
+suggesting O
+some O
+inhibitory O
+effect O
+. O
+
+Further O
+studies O
+suggested O
+that O
+low O
+dilutions O
+of O
+C5D B
+serum O
+contain O
+a O
+factor O
+( O
+or O
+factors O
+) O
+interfering O
+at O
+some O
+step O
+in O
+the O
+hemolytic O
+assay O
+of O
+C5 O
+, O
+rather O
+than O
+a O
+true O
+C5 O
+inhibitor O
+or O
+inactivator O
+. O
+
+Of O
+clinical O
+interest O
+are O
+( O
+a O
+) O
+the O
+documentation O
+of O
+membranous B
+glomerulonephritis I
+, O
+vasculitis B
+, O
+and O
+arthritis B
+in O
+an O
+individual O
+lacking O
+C5 O
+( O
+and O
+its O
+biologic O
+functions O
+) O
+, O
+and O
+( O
+b O
+) O
+a O
+remarkable O
+propensity O
+to O
+bacterial B
+infections I
+in O
+the O
+proband O
+, O
+even O
+during O
+periods O
+of O
+low O
+- O
+dose O
+or O
+alternate O
+- O
+day O
+corticosteroid O
+therapy O
+. O
+
+Other O
+observations O
+indicate O
+that O
+the O
+C5D B
+state O
+is O
+compatible O
+with O
+normal O
+coagulation O
+function O
+and O
+the O
+capacity O
+to O
+mount O
+a O
+neutrophilic B
+leukocytosis I
+during O
+pyogenic B
+infection I
+. O
+. O
+
+Susceptibility O
+to O
+ankylosing B
+spondylitis I
+in O
+twins O
+: O
+the O
+role O
+of O
+genes O
+, O
+HLA O
+, O
+and O
+the O
+environment O
+. O
+
+OBJECTIVE O
+To O
+determine O
+the O
+relative O
+effects O
+of O
+genetic O
+and O
+environmental O
+factors O
+in O
+susceptibility O
+to O
+ankylosing B
+spondylitis I
+( O
+AS B
+) O
+. O
+
+METHODS O
+Twins O
+with O
+AS B
+were O
+identified O
+from O
+the O
+Royal O
+National O
+Hospital O
+for O
+Rheumatic B
+Diseases I
+database O
+. O
+
+Clinical O
+and O
+radiographic O
+examinations O
+were O
+performed O
+to O
+establish O
+diagnoses O
+, O
+and O
+disease O
+severity O
+was O
+assessed O
+using O
+a O
+combination O
+of O
+validated O
+scoring O
+systems O
+. O
+
+HLA O
+typing O
+for O
+HLA O
+- O
+B27 O
+, O
+HLA O
+- O
+B60 O
+, O
+and O
+HLA O
+- O
+DR1 O
+was O
+performed O
+by O
+polymerase O
+chain O
+reaction O
+with O
+sequence O
+- O
+specific O
+primers O
+, O
+and O
+zygosity O
+was O
+assessed O
+using O
+microsatellite O
+markers O
+. O
+
+Genetic O
+and O
+environmental O
+variance O
+components O
+were O
+assessed O
+with O
+the O
+program O
+Mx O
+, O
+using O
+data O
+from O
+this O
+and O
+previous O
+studies O
+of O
+twins O
+with O
+AS B
+. O
+
+RESULTS O
+Six O
+of O
+8 O
+monozygotic O
+( O
+MZ O
+) O
+twin O
+pairs O
+were O
+disease O
+concordant O
+, O
+compared O
+with O
+4 O
+of O
+15 O
+B27 O
+- O
+positive O
+dizygotic O
+( O
+DZ O
+) O
+twin O
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+These O
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+A O
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+spot O
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+CD B
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+in O
+exon O
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+13 O
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+this O
+exon O
+. O
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+Seven O
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+We O
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+Our O
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+Deletion O
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+Cloning O
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+Based O
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+The O
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+Although O
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+On O
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+Mutations O
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+associated O
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+3 O
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+This O
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+In O
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+Sibships O
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+Where O
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+3 O
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+7 O
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+Studies O
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+Diagnosis O
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+Once O
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+iron O
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+Liver O
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+Currently O
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+detection O
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+family O
+members O
+of O
+patients O
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+a O
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+Epigenetic O
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+of O
+BRCA1 O
+proteins O
+, O
+reports O
+of O
+which O
+have O
+ranged O
+from O
+exclusively O
+nuclear O
+, O
+to O
+conditionally O
+nuclear O
+, O
+to O
+the O
+ER O
+/ O
+golgi O
+, O
+to O
+cytoplasmic O
+invaginations O
+into O
+the O
+nucleus O
+. O
+
+In O
+an O
+attempt O
+to O
+resolve O
+this O
+issue O
+, O
+we O
+have O
+comprehensively O
+characterized O
+19 O
+anti O
+- O
+BRCA1 O
+antibodies O
+. O
+
+These O
+reagents O
+detect O
+a O
+220 O
+- O
+kD O
+protein O
+localized O
+in O
+discrete O
+nuclear O
+foci O
+in O
+all O
+epithelial O
+cell O
+lines O
+, O
+including O
+those O
+derived O
+from O
+breast B
+malignancies I
+. O
+
+Immunohistochemical O
+staining O
+of O
+human O
+breast O
+specimens O
+also O
+revealed O
+BRCA1 O
+nuclear O
+foci O
+in O
+benign B
+breast I
+, I
+invasive I
+lobular I
+cancers I
+and O
+low O
+- O
+grade O
+ductal B
+carcinomas I
+. O
+
+Conversely O
+, O
+BRCA1 O
+expression O
+was O
+reduced O
+or O
+undetectable O
+in O
+the O
+majority O
+of O
+high O
+- O
+grade O
+, O
+ductal B
+carcinomas I
+, O
+suggesting O
+that O
+absence O
+of O
+BRCA1 O
+may O
+contribute O
+to O
+the O
+pathogenesis O
+of O
+a O
+significant O
+percentage O
+of O
+sporadic B
+breast I
+cancers I
+. O
+. O
+