Estimation of allele-specific fitness effects across human protein-coding sequences and implications for disease

Huang, Yi-Fei, Siepel, Adam (June 2019) Estimation of allele-specific fitness effects across human protein-coding sequences and implications for disease. Genome Research, 29 (8). pp. 1310-1321. ISSN 10889051 (ISSN)

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Abstract

A central challenge in human genomics is to understand the cellular, evolutionary, and clinical significance of genetic variants. Here we introduce a unified population-genetic and machine-learning model, called Linear Allele-Specific Selection InferencE (LASSIE), for estimating the fitness effects of all potential single-nucleotide variants, based on polymorphism data and predictive genomic features. We applied LASSIE to 51 high-coverage genome sequences annotated with 33 genomic features, and constructed a map of allele-specific selection coefficients across all protein-coding sequences in the human genome. We show that this map is informative about both human evolution and disease.

Item Type:	Paper
Subjects:	bioinformatics diseases & disorders bioinformatics > genomics and proteomics > genetics & nucleic acid processing bioinformatics > genomics and proteomics diseases & disorders > mental disorders diseases & disorders > neoplasms diseases & disorders > mental disorders > personality disorders bioinformatics > computational biology > algorithms diseases & disorders > mental disorders > personality disorders > autism bioinformatics > computational biology bioinformatics > genomics and proteomics > computers > computer software bioinformatics > computational biology > algorithms > machine learning bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > single nucleotide polymorphism
CSHL Authors:	Siepel, Adam Huang, Yifei
Communities:	CSHL labs > Siepel lab CSHL Cancer Center Program > Cancer Genetics and Genomics Program
Depositing User:	Matthew Dunn
Date:	27 June 2019
Date Deposited:	27 Nov 2018 16:56
Last Modified:	02 Feb 2024 15:48
PMCID:	PMC6673719
Related URLs:	bioRxiv Publisher
URI:	https://repository.cshl.edu/id/eprint/37482

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