Predicting the functional, molecular, and phenotypic consequences of amino acid substitutions using hidden Markov models.
Hashem A. Shihab,Julian Gough,David Neil Cooper,Peter D. Stenson,Gary L A Barker,Keith J. Edwards,Ian N. M. Day,Tom R. Gaunt +7 more
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TLDR
The Functional Analysis Through Hidden Markov Models (FATHMM) software and server is described: a species‐independent method with optional species‐specific weightings for the prediction of the functional effects of protein missense variants, demonstrating that FATHMM can be efficiently applied to high‐throughput/large‐scale human and nonhuman genome sequencing projects with the added benefit of phenotypic outcome associations.Abstract:
The rate at which nonsynonymous single nucleotide polymorphisms (nsSNPs) are being identified in the human genome is increasing dramatically owing to advances in whole-genome/whole-exome sequencing technologies. Automated methods capable of accurately and reliably distinguishing between pathogenic and functionally neutral nsSNPs are therefore assuming ever-increasing importance. Here, we describe the Functional Analysis Through Hidden Markov Models (FATHMM) software and server: a species-independent method with optional species-specific weightings for the prediction of the functional effects of protein missense variants. Using a model weighted for human mutations, we obtained performance accuracies that outperformed traditional prediction methods (i.e., SIFT, PolyPhen, and PANTHER) on two separate benchmarks. Furthermore, in one benchmark, we achieve performance accuracies that outperform current state-of-the-art prediction methods (i.e., SNPs&GO and MutPred). We demonstrate that FATHMM can be efficiently applied to high-throughput/large-scale human and nonhuman genome sequencing projects with the added benefit of phenotypic outcome associations. To illustrate this, we evaluated nsSNPs in wheat (Triticum spp.) to identify some of the important genetic variants responsible for the phenotypic differences introduced by intense selection during domestication. A Web-based implementation of FATHMM, including a high-throughput batch facility and a downloadable standalone package, is available at http://fathmm.biocompute.org.uk.read more
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Use of Recombinant CP2 and CP23 Antigens of Cryptosporidium parvum for Serodiagnosis of Human Cryptosporidiosis
TL;DR: In this article , the recombinant production of recombinant (r)P2 and rP23 antigens of C. parvum was reported for detecting human cryptosporidiosis using indirect ELISA tests.
Journal ArticleDOI
SWAAT Bioinformatics Workflow for Protein Structure-Based Annotation of ADME Gene Variants
TL;DR: The Structural Workflow for Annotating ADME Targets (SWAAT) is developed that allows for the prediction of the variant effect based on structural properties and outperformed six commonly used sequence-based variant prediction tools in terms of sensitivity and specificity.
Journal ArticleDOI
Association Between LTF Polymorphism and Risk of HIV-1 Transmission Among Zambian Seropositive Mothers.
TL;DR: M maternal LTF genetic background contributes to the susceptibility to HIV-1 transmission from mother to new-borns, and Maternal LTF T29A A/A and A/G genotypes were found to be associated with decreased risk of HIV- 1 MTCT.
Journal ArticleDOI
HPMPdb: A machine learning-ready database of protein molecular phenotypes associated to human missense variants
Daniele Raimondi,Francesco Codice,Gabriele Orlando,Joost Schymkowitz,Frederic Rousseau,Yves Moreau +5 more
TL;DR: HPMPdb as discussed by the authors is a manually curated database containing human Single Amino acid Variants (SAVs) associated with the detailed description of the molecular phenotype they cause on the affected proteins.
Dissertation
Etude du rôle de la voie NOTCH dans la régulation de Shh au cours du développement du cerveau antérieur chez les vertébrés
TL;DR: Des mutants souris hypomorphes pour the voie SHH et la voie NOTCH presentent des anomalies discretes de the ligne mediane correspondant a une dysplasie de the glande hypophysaire and une malformation de l’os basisphenoide.
References
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