Inferring perturbation profiles of cancer samples
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 gen...
| Main Authors: | , |
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| Format: | Article |
| Language: | English |
| Published: |
Oxford University Press
2021
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| Online Access: | View Fulltext in Publisher |
| Summary: | 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. © 2021 The Author(s) 2021. Published by Oxford University Press. |
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| ISBN: | 13674803 (ISSN) |
| DOI: | 10.1093/bioinformatics/btab113 |