Author:
Hsu Teng-Kuei,Asmussen Jennifer,Koire Amanda,Choi Byung-Kwon,Gadhikar Mayur A.,Huh Eunna,Lin Chih-Hsu,Konecki Daniel M.,Kim Young Won,Pickering Curtis R.,Kimmel Marek,Donehower Lawrence A.,Frederick Mitchell J.,Myers Jeffrey N.,Katsonis Panagiotis,Lichtarge Olivier
Abstract
Genetic variants drive the evolution of traits and diseases. We previously modeled these variants as small displacements in fitness landscapes and estimated their functional impact by differentiating the evolutionary relationship between genotype and phenotype. Conversely, here we integrate these derivatives to identify genes steering specific traits. Over cancer cohorts, integration identified 460 likely tumor-driving genes. Many have literature and experimental support but had eluded prior genomic searches for positive selection in tumors. Beyond providing cancer insights, these results introduce a general calculus of evolution to quantify the genotype–phenotype relationship and discover genes associated with complex traits and diseases.
Funder
National Institutes of Health
National Science Foundation
Gulf Coast Consortia
Biomedical Informatics & Data Science
Baylor College of Medicine Comprehensive Cancer Training Program
Baylor Research Advocates for Student Scientists
Publisher
Cold Spring Harbor Laboratory
Subject
Genetics (clinical),Genetics
Cited by
9 articles.
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