13 research outputs found
Semantic prioritization of novel causative genomic variants
Discriminating the causative disease variant(s) for individuals with inherited or de novo mutations presents one of the main challenges faced by the clinical genetics community today. Computational approaches for variant prioritization include machine learning methods utilizing a large number of features, including molecular information, interaction networks, or phenotypes. Here, we demonstrate the PhenomeNET Variant Predictor (PVP) system that exploits semantic technologies and automated reasoning over genotype-phenotype relations to filter and prioritize variants in whole exome and whole genome sequencing datasets. We demonstrate the performance of PVP in identifying causative variants on a large number of synthetic whole exome and whole genome sequences, covering a wide range of diseases and syndromes. In a retrospective study, we further illustrate the application of PVP for the interpretation of whole exome sequencing data in patients suffering from congenital hypothyroidism. We find that PVP accurately identifies causative variants in whole exome and whole genome sequencing datasets and provides a powerful resource for the discovery of causal variants.NS was funded by Wellcome Trust (Grant 100585/Z/12/Z) and the National Institute for Health Research Cambridge Biomedical Research Centre. IB, RBMR, MK, YH, VBB, RH were funded by the King Abdullah University of Science and Technology. GVG acknowledges funding from the National Science Foundation (NSF grant number: IOS-1340112) and the European Commision H2020 (Grant Agreement No. 731075)
The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens
Background: The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.
Results: Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole genome mutation screening in Candida albicans and aeruginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.
Conclusion: We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens
The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens
Background The Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function. Results Here, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory. Conclusion We conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.Peer reviewe
The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens
BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.</p
EFFICIENCY OF THE NEW MEDICATION OF FS-1 IN THE TREATMENT OF EXPERIMENTAL TUBERCULOSIS
In vitro studies have proved the anti-tuberculosis eect of FS-1 medication both against susceptible strain of M. tuberculosis H37Rv, and the strain of M. tuberculosis MS-115 with multiple drug resistance.Conducted in vivo studies on guinea pigs infected with the pathogenic culture of human tuberculosis (strain of H37Rv), have shown that FS-1 provides expressed anti-inflammatory action on the course of experimental tuberculosis
Эффективность нового лекарственного средства ФС-1 В лечении экспериментального туберкулеза
In vitro studies have proved the anti-tuberculosis eect of FS-1 medication both against susceptible strain of M. tuberculosis H37Rv, and the strain of M. tuberculosis MS-115 with multiple drug resistance.Conducted in vivo studies on guinea pigs infected with the pathogenic culture of human tuberculosis (strain of H37Rv), have shown that FS-1 provides expressed anti-inflammatory action on the course of experimental tuberculosis. В исследованиях in vitro установлен противотуберкулезный эффект лекарственного средства ФС-1 как в отношении чувствительного штамма M. tuberculosis H37Rv, так и штамма M. tuberculosis MS-115 с множественной лекарственной устойчивостью. Проведенные in vivo исследования на морских свинках, зараженных патогенной культурой туберкулеза человеческого вида (штамм H37Rv), показали, что ФС-1 оказывает выраженное противовоспалительное действие на течение экспериментального туберкулеза
Graph Based Automatic Protein Function Annotation Improved by Semantic Similarity
International audienc