Edgetic perturbation signatures represent known and novel cancer biomarkers
Open Access
- 9 March 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Scientific Reports
- Vol. 10 (1), 1-16
- https://doi.org/10.1038/s41598-020-61422-3
Abstract
Isoform switching is a recently characterized hallmark of cancer, and often translates to the loss or gain of domains mediating protein interactions and thus, the re-wiring of the interactome. Recent computational tools leverage domain-domain interaction data to resolve the condition-specific interaction networks from RNA-Seq data accounting for the domain content of the primary transcripts expressed. Here, we used The Cancer Genome Atlas RNA-Seq datasets to generate 642 patient-specific pairs of interactomes corresponding to both the tumor and the healthy tissues across 13 cancer types. The comparison of these interactomes provided a list of patient-specific edgetic perturbations of the interactomes associated with the cancerous state. We found that among the identified perturbations, select sets are robustly shared between patients at the multi-cancer, cancer-specific and cancer sub-type specific levels. Interestingly, the majority of the alterations do not directly involve significantly mutated genes, nevertheless, they strongly correlate with patient survival. The findings (available at EdgeExplorer: “http://webclu.bio.wzw.tum.de/EdgeExplorer”) are a new source of potential biomarkers for classifying cancer types and the proteins we identified are potential anti-cancer therapy targets.Keywords
Funding Information
- Deutsche Forschungsgemeinschaft (FR1411/14-1, FR1411/14-1)
- Deutscher Akademischer Austauschdienst (57196074)
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