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A general calculus of fitness landscapes finds genes under selection in cancers.
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.
Afiliación
  • Hsu TK; Department of Biochemistry and Molecular Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Asmussen J; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Koire A; Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Choi BK; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Gadhikar MA; Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  • Huh E; Department of Pharmacology and Chemical Biology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Lin CH; Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Konecki DM; Program in Quantitative and Computational Biosciences, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Kim YW; Program in Integrative Molecular and Biomedical Sciences, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Pickering CR; Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  • Kimmel M; Departments of Statistics and Bioengineering, Rice University, Houston, Texas 77005, USA.
  • Donehower LA; Department of Systems Engineering and Biology, Silesian University of Technology, 44-100 Gliwice, Poland.
  • Frederick MJ; Department of Molecular Virology and Microbiology, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Myers JN; Department of Otolaryngology-Head and Neck Surgery, Baylor College of Medicine, Houston, Texas 77030, USA.
  • Katsonis P; Department of Head and Neck Surgery, The University of Texas M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
  • Lichtarge O; Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas 77030, USA.
Genome Res ; 32(5): 916-929, 2022 05.
Article en En | MEDLINE | ID: mdl-35301263
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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cálculos / Neoplasias Límite: Humans Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Cálculos / Neoplasias Límite: Humans Idioma: En Revista: Genome Res Asunto de la revista: BIOLOGIA MOLECULAR / GENETICA Año: 2022 Tipo del documento: Article País de afiliación: Estados Unidos