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Schulte-Sasse, R.* ; Budach, S.* ; Hnisz, D.* ; Marsico, A.

Integration of multiomics data with graph convolutional networks to identify new cancer genes and their associated molecular mechanisms.

Nat. Mach. Intell. 3, 513–526 (2021)
DOI
Open Access Green as soon as Postprint is submitted to ZB.
The increase in available high-throughput molecular data creates computational challenges for the identification of cancer genes. Genetic as well as non-genetic causes contribute to tumorigenesis, and this necessitates the development of predictive models to effectively integrate different data modalities while being interpretable. We introduce EMOGI, an explainable machine learning method based on graph convolutional networks to predict cancer genes by combining multiomics pan-cancer data—such as mutations, copy number changes, DNA methylation and gene expression—together with protein–protein interaction (PPI) networks. EMOGI was on average more accurate than other methods across different PPI networks and datasets. We used layer-wise relevance propagation to stratify genes according to whether their classification was driven by the interactome or any of the omics levels, and to identify important modules in the PPI network. We propose 165 novel cancer genes that do not necessarily harbour recurrent alterations but interact with known cancer genes, and we show that they correspond to essential genes from loss-of-function screens. We believe that our method can open new avenues in precision oncology and be applied to predict biomarkers for other complex diseases.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
ISSN (print) / ISBN 2522-5839
e-ISSN 2522-5839
Journal Nature machine intelligence
Quellenangaben Volume: 3, Issue: , Pages: 513–526 Article Number: , Supplement: ,
Publisher Springer
Publishing Place [London]
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Computational Biology (ICB)
Grants IMPRS