Inferring perturbation profiles of cancer samples

Abstract Motivation Cancer is one of the most prevalent diseases in the world. Tumors arise due to important genes changing their activity, e.g. when inhibited or over-expressed. But these gene perturbations are difficult to observe directly. Molecular profiles of tumors can provide indirect evidenc...

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Bibliographic Details
Published in:Bioinformatics (Oxford, England) England), 2021-08, Vol.37 (16), p.2441-2449
Main Authors: Pirkl, Martin, Beerenwinkel, Niko
Format: Article
Language:English
Subjects:
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Bioinformatics
Cancer
CRISPR
Error analysis
Gene expression
Genes
Original Papers
Perturbation
Tumors
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Summary:Abstract Motivation Cancer is one of the most prevalent diseases in the world. Tumors arise due to important genes changing their activity, e.g. when inhibited or over-expressed. But these gene perturbations are difficult to observe directly. Molecular profiles of tumors can provide indirect evidence of gene perturbations. However, inferring perturbation profiles from molecular alterations is challenging due to error-prone molecular measurements and incomplete coverage of all possible molecular causes of gene perturbations. Results We have developed a novel mathematical method to analyze cancer driver genes and their patient-specific perturbation profiles. We combine genetic aberrations with gene expression data in a causal network derived across patients to infer unobserved perturbations. We show that our method can predict perturbations in simulations, CRISPR perturbation screens and breast cancer samples from The Cancer Genome Atlas. Availability and implementation The method is available as the R-package nempi at https://github.com/cbg-ethz/nempi and http://bioconductor.org/packages/nempi. Supplementary information Supplementary data are available at Bioinformatics online.
ISSN:1367-4803
1367-4811
DOI:10.1093/bioinformatics/btab113