Functional variomics and network perturbation

Connecting genotype to phenotype in cancer

Song Yi, Shengda Lin, Yongsheng Li, Wei Zhao, Gordon Mills, Nidhi Sahni

Research output: Contribution to journalReview article

28 Citations (Scopus)

Abstract

Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants, including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signalling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.

Original languageEnglish (US)
Pages (from-to)395-410
Number of pages16
JournalNature Reviews Genetics
Volume18
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

Fingerprint

Genotype
Phenotype
Mutation
Neoplasms
Genes
Neoplasm Genes
Base Pairing
Signal Transduction
Proteins
Population

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Functional variomics and network perturbation : Connecting genotype to phenotype in cancer. / Yi, Song; Lin, Shengda; Li, Yongsheng; Zhao, Wei; Mills, Gordon; Sahni, Nidhi.

In: Nature Reviews Genetics, Vol. 18, No. 7, 01.07.2017, p. 395-410.

Research output: Contribution to journalReview article

Yi, Song ; Lin, Shengda ; Li, Yongsheng ; Zhao, Wei ; Mills, Gordon ; Sahni, Nidhi. / Functional variomics and network perturbation : Connecting genotype to phenotype in cancer. In: Nature Reviews Genetics. 2017 ; Vol. 18, No. 7. pp. 395-410.
@article{1c7071c39f0847a6be5d09df00e75f19,
title = "Functional variomics and network perturbation: Connecting genotype to phenotype in cancer",
abstract = "Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants, including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signalling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.",
author = "Song Yi and Shengda Lin and Yongsheng Li and Wei Zhao and Gordon Mills and Nidhi Sahni",
year = "2017",
month = "7",
day = "1",
doi = "10.1038/nrg.2017.8",
language = "English (US)",
volume = "18",
pages = "395--410",
journal = "Nature Reviews Genetics",
issn = "1471-0056",
publisher = "Nature Publishing Group",
number = "7",

}

TY - JOUR

T1 - Functional variomics and network perturbation

T2 - Connecting genotype to phenotype in cancer

AU - Yi, Song

AU - Lin, Shengda

AU - Li, Yongsheng

AU - Zhao, Wei

AU - Mills, Gordon

AU - Sahni, Nidhi

PY - 2017/7/1

Y1 - 2017/7/1

N2 - Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants, including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signalling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.

AB - Proteins interact with other macromolecules in complex cellular networks for signal transduction and biological function. In cancer, genetic aberrations have been traditionally thought to disrupt the entire gene function. It has been increasingly appreciated that each mutation of a gene could have a subtle but unique effect on protein function or network rewiring, contributing to diverse phenotypic consequences across cancer patient populations. In this Review, we discuss the current understanding of cancer genetic variants, including the broad spectrum of mutation classes and the wide range of mechanistic effects on gene function in the context of signalling networks. We highlight recent advances in computational and experimental strategies to study the diverse functional and phenotypic consequences of mutations at the base-pair resolution. Such information is crucial to understanding the complex pleiotropic effect of cancer genes and provides a possible link between genotype and phenotype in cancer.

UR - http://www.scopus.com/inward/record.url?scp=85016098512&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85016098512&partnerID=8YFLogxK

U2 - 10.1038/nrg.2017.8

DO - 10.1038/nrg.2017.8

M3 - Review article

VL - 18

SP - 395

EP - 410

JO - Nature Reviews Genetics

JF - Nature Reviews Genetics

SN - 1471-0056

IS - 7

ER -