A general calculus of fitness landscapes finds genes under selection in cancers

Teng Kuei Hsu; Jennifer Asmussen; Amanda Koire; Byung Kwon Choi; Mayur A. Gadhikar; Eunna Huh; Chih Hsu Lin; Daniel M. Konecki; Young Won Kim; Curtis R. Pickering; Marek Kimmel; Lawrence A. Donehower; Mitchell J. Frederick; Jeffrey N. Myers; Panagiotis Katsonis; Olivier Lichtarge

doi:10.1101/gr.275811.121

A general calculus of fitness landscapes finds genes under selection in cancers

Teng Kuei Hsu, Jennifer Asmussen, Amanda Koire, Byung Kwon Choi, Mayur A. Gadhikar, Eunna Huh, Chih Hsu Lin, Daniel M. Konecki, Young Won Kim, Curtis R. Pickering, Marek Kimmel, Lawrence A. Donehower, Mitchell J. Frederick, Jeffrey N. Myers, Panagiotis Katsonis, Olivier Lichtarge

Head & Neck Surgery

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

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.

Original language	English (US)
Pages (from-to)	916-929
Number of pages	14
Journal	Genome research
Volume	32
Issue number	5
DOIs	https://doi.org/10.1101/gr.275811.121
State	Published - May 2022

ASJC Scopus subject areas

Genetics
Genetics(clinical)

Access to Document

10.1101/gr.275811.121

Cite this

Hsu, T. K., Asmussen, J., Koire, A., Choi, B. K., Gadhikar, M. A., Huh, E., Lin, C. H., Konecki, D. M., Kim, Y. W., Pickering, C. R., Kimmel, M., Donehower, L. A., Frederick, M. J., Myers, J. N., Katsonis, P., & Lichtarge, O. (2022). A general calculus of fitness landscapes finds genes under selection in cancers. Genome research, 32(5), 916-929. https://doi.org/10.1101/gr.275811.121

@article{5b744b1ef996429b9a9849856298d9da,

title = "A general calculus of fitness landscapes finds genes under selection in cancers",

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.",

author = "Hsu, {Teng Kuei} and Jennifer Asmussen and Amanda Koire and Choi, {Byung Kwon} and Gadhikar, {Mayur A.} and Eunna Huh and Lin, {Chih Hsu} and Konecki, {Daniel M.} and Kim, {Young Won} and Pickering, {Curtis R.} and Marek Kimmel and Donehower, {Lawrence A.} and Frederick, {Mitchell J.} and Myers, {Jeffrey N.} and Panagiotis Katsonis and Olivier Lichtarge",

note = "Publisher Copyright: {\textcopyright} 2022 Hsu et al.",

year = "2022",

month = may,

doi = "10.1101/gr.275811.121",

language = "English (US)",

volume = "32",

pages = "916--929",

journal = "Genome research",

issn = "1088-9051",

publisher = "Cold Spring Harbor Laboratory Press",

number = "5",

}

TY - JOUR

T1 - A general calculus of fitness landscapes finds genes under selection in cancers

AU - Hsu, Teng Kuei

AU - Asmussen, Jennifer

AU - Koire, Amanda

AU - Choi, Byung Kwon

AU - Gadhikar, Mayur A.

AU - Huh, Eunna

AU - Lin, Chih Hsu

AU - Konecki, Daniel M.

AU - Kim, Young Won

AU - Pickering, Curtis R.

AU - Kimmel, Marek

AU - Donehower, Lawrence A.

AU - Frederick, Mitchell J.

AU - Myers, Jeffrey N.

AU - Katsonis, Panagiotis

AU - Lichtarge, Olivier

PY - 2022/5

Y1 - 2022/5

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=85129160148&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85129160148&partnerID=8YFLogxK

U2 - 10.1101/gr.275811.121

DO - 10.1101/gr.275811.121

M3 - Article

C2 - 35301263

AN - SCOPUS:85129160148

SN - 1088-9051

VL - 32

SP - 916

EP - 929

JO - Genome research

JF - Genome research

IS - 5

ER -

A general calculus of fitness landscapes finds genes under selection in cancers

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this