Dec 14, 2018

A multi-omics approach for identifying important pathways and genes in human cancer

BMC Bioinformatics
H Robert Frost, Christopher I Amos

Abstract

Cancer develops when pathways controlling cell survival, cell fate or genome maintenance are disrupted by the somatic alteration of key driver genes. Understanding how pathway disruption is driven by somatic alterations is thus essential for an accurate characterization of cancer biology and identification of therapeutic targets. Unfortunately, current cancer pathway analysis methods fail to fully model the relationship between somatic alterations and pathway activity. To address these limitations, we developed a multi-omics method for identifying biologically important pathways and genes in human cancer. Our approach combines single-sample pathway analysis with multi-stage, lasso-penalized regression to find pathways whose gene expression can be explained largely in terms of gene-level somatic alterations in the tumor. Importantly, this method can analyze case-only data sets, does not require information regarding pathway topology and supports personalized pathway analysis using just somatic alteration data for a limited number of cancer-associated genes. The practical effectiveness of this technique is illustrated through an analysis of data from The Cancer Genome Atlas using gene sets from the Molecular Signatures Database. ...Continue Reading

Mentioned in this Paper

Regulation of Cell-cell Adhesion
Biochemical Pathway
Genome
Genes
Somatic Mutation
Diseases Database
Neoplasms
Research Methodology
Gene Expression
Genomics

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