bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome-wide identification of specific oligonucleotides using artificial neural network and computational genomic analysis
Authors: Liu Chun-Chi , Lin Chin-Chung , Li Ker-Chau , Chen Wen-Shyen E , Chen Jiun-Ching , Yang Ming-Te , Yang Pan-Chyr , Chang Pei-Chun , Chen Jeremy JW 
Published: May 2007

Abstract

Background
Genome-wide identification of specific oligonucleotides (oligos) is a computationally-intensive task and is a requirement for designing microarray probes, primers, and siRNAs. An artificial neural network (ANN) is a machine learning technique that can effectively process complex and high noise data. Here, ANNs are applied to process the unique subsequence distribution for prediction of specific oligos.

Results
We present a novel and efficient algorithm, named the integration of ANN and BLAST (IAB) algorithm, to identify specific oligos. We establish the unique marker database for human and rat gene index databases using the hash table algorithm. We then create the input vectors, via the unique marker database, to train and test the ANN. The trained ANN predicted the specific oligos with high efficiency, and these oligos were subsequently verified by BLAST. To improve the prediction performance, the ANN over-fitting issue was avoided by early stopping with the best observed error and a k-fold validation was also applied. The performance of the IAB algorithm was about 5.2, 7.1, and 6.7 times faster than the BLAST search without ANN for experimental results of 70-mer, 50-mer, and 25-mer specific oligos, respectively. In addition, the results of polymerase chain reactions showed that the primers predicted by the IAB algorithm could specifically amplify the corresponding genes. The IAB algorithm has been integrated into a previously published comprehensive web server to support microarray analysis and genome-wide iterative enrichment analysis, through which users can identify a group of desired genes and then discover the specific oligos of these genes.

Conclusion
The IAB algorithm has been developed to construct SpecificDB, a web server that provides a specific and valid oligo database of the probe, siRNA, and primer design for the human genome. We also demonstrate the ability of the IAB algorithm to predict specific oligos through polymerase chain reaction experiments. SpecificDB provides comprehensive information and a user-friendly interface.
Hinge Atlas: relating protein sequence to sites of structural flexibility
Authors: Flores Samuel C , Lu Long J , Yang Julie , Carriero Nicholas , Gerstein Mark B 
Published: May 2007

Abstract

Background
Relating features of protein sequences to structural hinges is important for identifying domain boundaries, understanding structure-function relationships, and designing flexibility into proteins. Efforts in this field have been hampered by the lack of a proper dataset for studying characteristics of hinges.

Results
Using the Molecular Motions Database we have created a Hinge Atlas of manually annotated hinges and a statistical formalism for calculating the enrichment of various types of residues in these hinges.

Conclusion
We found various correlations between hinges and sequence features. Some of these are expected; for instance, we found that hinges tend to occur on the surface and in coils and turns and to be enriched with small and hydrophilic residues. Others are less obvious and intuitive. In particular, we found that hinges tend to coincide with active sites, but unlike the latter they are not at all conserved in evolution. We evaluate the potential for hinge prediction based on sequence.
Motions play an important role in catalysis and protein-ligand interactions. Hinge bending motions comprise the largest class of known motions. Therefore it is important to relate the hinge location to sequence features such as residue type, physicochemical class, secondary structure, solvent exposure, evolutionary conservation, and proximity to active sites. To do this, we first generated the Hinge Atlas, a set of protein motions with the hinge locations manually annotated, and then studied the coincidence of these features with the hinge location. We found that all of the features have bearing on the hinge location. Most interestingly, we found that hinges tend to occur at or near active sites and yet unlike the latter are not conserved. Less surprisingly, we found that hinge residues tend to be small, not hydrophobic or aliphatic, and occur in turns and random coils on the surface. A functional sequence based hinge predictor was made which uses some of the data generated in this study. The Hinge Atlas is made available to the community for further flexibility studies.
A feature selection approach for identification of signature genes from SAGE data
Authors: Barrera Junior , Cesar Roberto M , Humes Carlos , Martins David C , Patrão Diogo FC , Silva Paulo JS , Brentani Helena 
Published: May 2007

Abstract

Background
One goal of gene expression profiling is to identify signature genes that robustly distinguish different types or grades of tumors. Several tumor classifiers based on expression profiling have been proposed using microarray technique. Due to important differences in the probabilistic models of microarray and SAGE technologies, it is important to develop suitable techniques to select specific genes from SAGE measurements.

Results
A new framework to select specific genes that distinguish different biological states based on the analysis of SAGE data is proposed. The new framework applies the bolstered error for the identification of strong genes that separate the biological states in a feature space defined by the gene expression of a training set. Credibility intervals defined from a probabilistic model of SAGE measurements are used to identify the genes that distinguish the different states with more reliability among all gene groups selected by the strong genes method. A score taking into account the credibility and the bolstered error values in order to rank the groups of considered genes is proposed. Results obtained using SAGE data from gliomas are presented, thus corroborating the introduced methodology.

Conclusion
The model representing counting data, such as SAGE, provides additional statistical information that allows a more robust analysis. The additional statistical information provided by the probabilistic model is incorporated in the methodology described in the paper. The introduced method is suitable to identify signature genes that lead to a good separation of the biological states using SAGE and may be adapted for other counting methods such as Massive Parallel Signature Sequencing (MPSS) or the recent Sequencing-By-Synthesis (SBS) technique. Some of such genes identified by the proposed method may be useful to generate classifiers.
Gene function prediction based on genomic context clustering and discriminative learning: an application to bacteriophages
Authors: Li Jason , Halgamuge Saman K , Kells Christopher I , Tang Sen-Lin 
Published: May 2007

Abstract

Background
Existing methods for whole-genome comparisons require prior knowledge of related species and provide little automation in the function prediction process. Bacteriophage genomes are an example that cannot be easily analyzed by these methods. This work addresses these shortcomings and aims to provide an automated prediction system of gene function.

Results
We have developed a novel system called SynFPS to perform gene function prediction over completed genomes. The prediction system is initialized by clustering a large collection of weakly related genomes into groups based on their resemblance in gene distribution. From each individual group, data are then extracted and used to train a Support Vector Machine that makes gene function predictions. Experiments were conducted with 9 different gene functions over 296 bacteriophage genomes. Cross validation results gave an average prediction accuracy of ~80%, which is comparable to other genomic-context based prediction methods. Functional predictions are also made on 3 uncharacterized genes and 12 genes that cannot be identified by sequence alignment. The software is publicly available at http://www.synteny.net/.

Conclusion
The proposed system employs genomic context to predict gene function and detect gene correspondence in whole-genome comparisons. Although our experimental focus is on bacteriophages, the method may be extended to other microbial genomes as they share a number of similar characteristics with phage genomes such as gene order conservation.
Mutation accumulation and fitness effects in hybridogenetic populations: a comparison to sexual and asexual systems
Authors: Som Christian , Bagheri Homayoun C , Reyer Heinz-Ulrich 
Published: May 2007

Abstract

Background
Female only unisexual vertebrates that reproduce by hybridogenesis show an unusual genetic composition. They are of hybrid origin but show no recombination between the genomes of their parental species. Instead, the paternal genome is discarded from the germline prior to meiosis, and gametes (eggs only) contain solely unrecombined maternal genomes. Hence hybridogens only transmit maternally inherited mutations. Hybridity is restored each generation by backcrossing with males of the sexual parental species whose genome was eliminated. In contrast, recombining sexual species propagate an intermixed pool of mutations derived from the maternal and paternal parts of the genome. If mutation rates are lower in female gametes than males, it raises the possibility for lower mutation accumulation in a hybridogenetic population, and consequently, higher population fitness than its sexual counterpart.

Results
We show through Monte-Carlo simulations that at higher male to female mutation ratios, and sufficiently large population sizes, hybridogenetic populations can carry a lower mutation load than sexual species. This effect is more pronounced with synergistic forms of epistasis. Mutations accumulate faster on the sexual part of the genome, and with the purifying effects of epistasis, it makes it more difficult for mutations to be transmitted on the clonal part of the genome. In smaller populations, the same mechanism reduces the speed of Muller's Ratchet and the number of fixed mutations compared to similar asexual species.

Conclusion
Since mutation accumulation can be less pronounced in hybridogenetic populations, the question arises why hybridogenetic organisms are so scarce compared to sexual species. In considering this, it is likely that comparison of population fitnesses is not sufficient. Despite competition with the sexual parental species, hybrid populations are dependent on the maintenance of – and contact with – their sexual counterpart. Other problems may involve too little genetic diversity to respond to changing environments and problems in becoming hybridogenetic (e.g. disruption of meiosis and subsequent infertility or sterility). Yet, lower mutation accumulation in hybridogenetic populations opens the possibility that hybridogenetic species can develop into new sexual species once recombination is re-established and reproductive isolation from sexual ancestors has occurred.
Toxin production in a rare and genetically remote cluster of strains of the Bacillus cereus group
Authors: Fagerlund Annette , Brillard Julien , Fürst Rainer , Guinebretière Marie-Hélène , Granum Per Einar 
Published: May 2007

Abstract

Background
Three enterotoxins are implicated in diarrhoeal food poisoning due to Bacillus cereus: Haemolysin BL (Hbl), Non-haemolytic enterotoxin (Nhe), and Cytotoxin K (CytK). Toxin gene profiling and assays for detection of toxin-producing stains have been used in attempts to evaluate the enterotoxic potential of B. cereus group strains. B. cereus strain NVH 391/98, isolated from a case of fatal enteritis, was genetically remote from other B. cereus group strains. This strain lacked the genes encoding Hbl and Nhe, but contains CytK-1. The high virulence of this strain is thought to be due to the greater cytotoxic activity of CytK-1 compared to CytK-2, and to a high level of cytK expression. To date, only three strains containing cytK-1 have been identified; B. cereus strains NVH 391/98, NVH 883/00, and INRA AF2.

Results
A novel gene variant encoding Nhe was identified in these three strains, which had an average of 80% identity in protein sequence with previously identified Nhe toxins. While culture supernatants containing CytK and Nhe from NVH 391/98 and INRA AF2 were highly cytotoxic, NVH 883/00 expressed little or no CytK and Nhe and was non-cytotoxic. Comparative sequence and expression studies indicated that neither the PlcR/PapR quorum sensing system, nor theYvrGH and YvfTU two-component systems, were responsible for the observed difference in toxin production. Additionally, phylogenetic analysis of 13 genes showed that NVH 391/98, NVH 883/00, and INRA AF2 comprise a novel cluster of strains genetically distant from other B. cereus group strains.

Conclusion
Due to its divergent sequence, the novel nhe operon had previously not been detected in NVH 391/98 using PCR and several monoclonal antibodies. Thus, toxigenic profiling based on the original nhe sequence will fail to detect the toxin in this group of strains. The observation that strain NVH 883/00 carries cytK-1 but is non-cytotoxic indicates that the detection of this gene variant is not a sufficient criterion for identification of highly cytotoxic strains. The presence of the novel nhe operon and the cytK-1 gene variant in this cluster of strains reflect their phylogenetically remote relationship towards other B. cereus group strains.
Quantification of malaria parasite release from infected erythrocytes: inhibition by protein-free media
Authors: Glushakova Svetlana , Yin Dan , Gartner Nicole , Zimmerberg Joshua 
Published: May 2007

Abstract

Background
Intracellular malaria parasites leave their host erythrocytes to infect neighbouring cells after each cycle of asexual replication. No method is currently available for the direct quantification of parasite release.

Method and results
To quantify parasite release process, human erythrocytes infected with Plasmodium falciparum were injected into sealed chambers at optimal density, where they progressed through the end of the erythrocyte cycle. Each event of parasite release inside the chamber at the site of erythrocyte rupture leaves on the chamber wall a footprint, composed of 1) separated parasites, 2) a digestive vacuole with haemozoin, and 3) fragments of the ruptured membranes. These footprints are stable for hours, allowing precise identification using differential interference contrast (DIC) microscopy. The relative rate of parasite release is defined as the percent of such footprints out of all schizonts injected and incubated into chamber at 37°C for two hours. The method is highly reproducible, easy to perform, and does not require expensive equipment. Additionally, this method allows one to analyse cell and release site morphology, which adds information about the release process and the quality of the culture. The method is used here to show that swelling of schizonts caused by protein-free media inhibits parasite release.

Conclusion
In this study, a novel method is described to count sites of parasite release by microscopy. Besides the direct estimation of parasite release from infected erythrocytes, this method provides a morphological evaluation of normal infected cells approaching the end of the plasmodial life cycle, or pathological forms accumulated as the result of experimental intervention in the parasite release process. One may now accurately estimate the relative parasite release rate at the time of cycle transition, without any obligatory coupling to parasite invasion.
Serum procalcitonin measurement as diagnostic and prognostic marker in febrile adult patients presenting to the emergency department
Authors: Hausfater Pierre , Juillien Gaëlle , Madonna-Py Beatrice , Haroche Julien , Bernard Maguy , Riou Bruno 
Published: May 2007

Abstract
Introduction
Identification of bacterial infections is crucial if treatment is to be initiated early and antibiotics used rationally. The primary objective of this study was to test the efficiency of procalcitonin (PCT) in identifying bacterial/parasitic episodes among febrile adult patients presenting to an emergency department. Secondary objectives were to identify clinical or biological variables associated with either bacterial/parasitic infection or critical illness.

Methods
This was a prospective, single centre, non-interventional study, conducted in the adult emergency department of an academic tertiary care hospital. We included patients with body temperature of 38.5°C or greater. A serum sample for measurement of PCT was collected in the emergency room. Patients were followed up until day 30. After reviewing the medical files, two independent experts, who were blind to the PCT results, classified each of the patients as having a bacterial/parasitic infection, viral infection, or another diagnosis.

Results
Among 243 patients included in the study, 167 had bacterial/parasitic infections, 35 had viral infections and 41 had other diagnoses. The PCT assay, with a 0.2 μg/l cutoff value, had a sensitivity of 0.77 and a specificity of 0.59 in diagnosing bacterial/parasitic infection. Of the patients with PCT 5 μg/l or greater, 51% had critical illness (death or intensive care unit admission) as compared with 13% of patients with lower PCT values.

Conclusion
Bearing in mind the limitations of an observational study design, the judgements of the emergency department physicians were reasonably accurate in determining the pretest probability of bacterial/parasitic infection. PCT may provide additional, valuable information on the aetiology and prognosis of infection in the emergency department.
Monitoring of gene knockouts: genome-wide profiling of conditionally essential genes
Authors: Smith Lisa K , Gomez Maria J , Shatalin Konstantin Y , Lee Hyunwoo , Neyfakh Alexander A 
Published: May 2007

AbstractWe have developed a new microarray-based genetic technique, named MGK (Monitoring of Gene Knockouts), for genome-wide identification of conditionally essential genes. MGK identified bacterial genes that are critical for fitness in the absence of aromatic amino acids, and was further applied to identify genes whose inactivation causes bacterial cell death upon exposure to the bacteriostatic antibiotic chloramphenicol. Our findings suggest that MGK can serve as a robust tool in functional genomics studies.
GSMN-TB: a web-based genome-scale network model of Mycobacterium tuberculosismetabolism
Authors: Beste Dany JV , Hooper Tracy , Stewart Graham , Bonde Bhushan , Avignone-Rossa Claudio , Bushell Michael E , Wheeler Paul , Klamt Steffen , Kierzek Andrzej M , McFadden Johnjoe 
Published: May 2007

Abstract
Background
An impediment to the rational development of novel drugs against tuberculosis (TB) is a general paucity of knowledge concerning the metabolism of Mycobacterium tuberculosis, particularly during infection. Constraint-based modeling provides a novel approach to investigating microbial metabolism but has not yet been applied to genome-scale modeling of M. tuberculosis.

Results
GSMN-TB, a genome-scale metabolic model of M. tuberculosis, was constructed, consisting of 849 unique reactions and 739 metabolites, and involving 726 genes. The model was calibrated by growing Mycobacterium bovis bacille Calmette Guérin in continuous culture and steady-state growth parameters were measured. Flux balance analysis was used to calculate substrate consumption rates, which were shown to correspond closely to experimentally determined values. Predictions of gene essentiality were also made by flux balance analysis simulation and were compared with global mutagenesis data for M. tuberculosis grown in vitro. A prediction accuracy of 78% was achieved. Known drug targets were predicted to be essential by the model. The model demonstrated a potential role for the enzyme isocitrate lyase during the slow growth of mycobacteria, and this hypothesis was experimentally verified. An interactive web-based version of the model is available.

Conclusion
The GSMN-TB model successfully simulated many of the growth properties of M. tuberculosis. The model provides a means to examine the metabolic flexibility of bacteria and predict the phenotype of mutants, and it highlights previously unexplored features of M. tuberculosis metabolism.
A systematic comparative and structural analysis of protein phosphorylation sites based on the mtcPTM database
Authors: Jiménez José L , Hegemann Björn , Hutchins James RA , Peters Jan-Michael , Durbin Richard 
Published: May 2007

AbstractmtcPTM is an online repository of human and mouse phosphosites in which data are hierarchically organized to preserve biologically relevant experimental information, thus allowing straightforward comparisons of phosphorylation patterns found under different conditions. The database also contains the largest available collection of atomic models of phosphorylatable proteins. Detailed analysis of this structural dataset reveals that phosphorylation sites are found in a heterogeneous range of structural and sequence contexts. mtcPTM is available on the web http://www.mitocheck.org/cgi-bin/mtcPTM/search.
Multicenter Phase II Trial of Neoadjuvant Therapy With Trastuzumab, Docetaxel, and Carboplatin for Human Epidermal Growth Factor Receptor-2–Overexpressing Stage II or III Breast Cancer: Results of the GETN(A)-1 Trial
Authors: Coudert Bruno P. , Largillier Remy , Arnould Laurent , Chollet Philippe , Campone Mario , Coeffic David , Priou Frank , Gligorov Joseph , Martin Xavier , Trillet-Lenoir Véronique , Weber Béatrice , Bleuse Jean Pierre , Vasseur Berangère , Serin Daniel , Namer Moïse 
Published: May 2007

Purpose Trastuzumab plus chemotherapy has become the standard of care for human epidermal growth factor receptor-2 (HER-2) –positive breast cancer. Trastuzumab-based preoperative systemic therapy (PST; neoadjuvant therapy) also appears promising, warranting further investigation. Patients and Methods Patients with HER-2-positive, stage II/III, noninflammatory, operable breast cancer requiring a mastectomy (but who wanted to conserve the breast) received trastuzumab 4 mg/kg (day 1), followed by 2 mg/kg weekly, plus docetaxel 75 mg/m2 every 3 weeks, and carboplatin (area under curve, 6) for six cycles before surgery. The primary end point was pathologic complete response (pCR) rate, determined from surgical specimens. Results Seventy patients were enrolled. Most patients had clinical T2/T3 tumors (100%) or clinical N1/2 nodes (53%). Sixty-seven patients (96%) completed six cycles of therapy, one patient withdrew due to progressive disease, and two patients withdrew for toxicity. A complete or partial objective clinical response occurred in 95% of patients (85% and 10%, respectively). Surgery was breast conservative in 45 (64%) of 70 patients. In an intent-to-treat analysis, tumor and nodal pCR were seen in 27 (39%) of 70 patients. Centralized retrospective analysis of HER-2 status demonstrated a 43% pCR rate in the 24 of 56 confirmed HER-2-overexpressing (3+) and/or fluorescence in situ hybridization–positive tumors. Treatment was generally well tolerated. Grade 3/4 neutropenia and febrile neutropenia were uncommon (2%). Two patients withdrew prematurely due to a transient, asymptomatic decrease in left ventricular ejection fraction. No symptomatic cardiac dysfunction occurred. Conclusion PST with trastuzumab plus docetaxel and carboplatin achieved promising efficacy, with a good pCR rate and favorable tolerability in stage II or III HER-2-positive breast cancer.