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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Identification of Somatic Mutations in Thirty-year-old Serum Cell-free DNA From Patients With Breast Cancer: A Feasibility Study.
Mathilde Ritter,Viola Paradiso,Patrik Widmer,Andrea Garofoli,Luca Quagliata,Serenella Eppenberger-Castori,Savas D. Soysal,Simone Muenst,Charlotte K.Y. Ng,Salvatore Piscuoglio,Walter Weber,Walter P. Weber +11 more
TL;DR: The present study shows that current next generation sequencing technology is sufficiently robust and specific to analyze 30-year-old serum, and longitudinal studies can be designed with storage of serum samples over many years, thereby obviating the need for timely and continuous cfDNA extraction and sequencing.
Posted ContentDOI
MutaFrame - an interpretative visualization framework for deleteriousness prediction of missense variants in the human exome
TL;DR: MundaFrame as discussed by the authors is a web-server that offers two deleteriousness prediction softwares, DEOGEN2 and SNPMuSiC, and is designed for bioinformaticians and medical researchers who want to gain insights into the origins of monogenic diseases.
Journal ArticleDOI
PTBP2 – a gene with relevance for both Anorexia nervosa and body weight regulation
Yiran Zheng,L. S. Rajcsanyi,Beate Herpertz-Dahlmann,Jochen Seitz,Martina de Zwaan,Wolfgang Herzog,Stefan Ehrlich,Stephan Zipfel,Katrin Elisabeth Giel,Karin Egberts,Roland Burghardt,Manuel Föcker,Saad Al-Lahham,Triinu Peters,Lars Libuda,Jochen Antel,Johannes Hebebrand,Anke Hinney +17 more
TL;DR: Pulit et al. as mentioned in this paper found that the polypyrimidine tract binding protein 2 gene (PTBP2) may have a more pronounced effect on body weight regulation in males than in females.
Journal Article
The evolutionary history of human colitis-associated colorectal cancer
Baker A-M.,William Cross,K Curtius,Choi C-Hr.,Ibrahim Al-Bakir,Daniel Temko,Pierre Martinez,Marc S. Williams,H Davis,Sujata Biswas,Nicholas A. Wright,Morgan Moorghen,Stephen J. Hayes,Manuel Rodriguez-Justo,Andrew Silver,Lai Mun Wang,Marnix Jansen,Ailsa Hart,Simon J. Leedham,Trevor A. Graham +19 more
TL;DR: Evolutionary genomic analysis revealed precancer clones bearing extensive SNAs and CNAs, with progression to cancer involving a dramatic accrual of CNAs at HGD, but punctuated evolution may limit the window for early detection.
Journal ArticleDOI
Comprehensive Characterization of Stage IIIA Non-Small Cell Lung Carcinoma.
Neetu Singh,Archana Mishra,Dinesh Kumar Sahu,Mayank Jain,Hari Shyam,Ratnesh Kumar Tripathi,Pratap Shankar,Anil Kumar,Nawazish Alam,Riddhi Jaiswal,Shailendra Kumar +10 more
TL;DR: A transcript-based signature to categorize stage IIIA-NSCLC in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC) plus markers that could indicate the prognosis of the disease are developed to understand the pathophysiology of NSCLC.
References
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