This repository contains manually curated causal interactions to describe cancer signaling events and is compliant with the annotation standard established by the SIGNOR database.
There are different versions of the CASCADE topology:
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CASCADE 1.0 (75 nodes, 149 directed interactions). GINsim files are available at the respective GINsim model repository. This version was featured in Flobak et al. (2015). Discovery of Drug Synergies in Gastric Cancer Cells Predicted by Logical Modeling. PLOS Computational Biology, 11(8), e1004426. https://doi.org/10.1371/journal.pcbi.1004426
Note that a slight different version of this topology (some nodes were renamed, with a total of 77 nodes and 149 interactions) was used as a base file to build the later versions - see cascade_1.0.sif and cascade_1.0.svg).
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CASCADE 2.0 (144 nodes and 367 interactions - see cascade_2.0.tsv and cascade_2.0.sif). This version was featured in Niederdorfer et al. (2020). Strategies to Enhance Logic Modeling-Based Cell Line-Specific Drug Synergy Prediction. Frontiers in Physiology, 11, 862. https://doi.org/10.3389/fphys.2020.00862
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CASCADE 3.0 (183 nodes and 603 interactions - see respective directory with files). This version was featured in Tsirvouli et al. (2020). A middle-out modeling strategy to extend a colon cancer logical model improves drug synergy predictions in epithelial-derived cancer cell lines. Frontiers in Molecular Biosciences, 7, 300. https://doi.org/10.3389/fmolb.2020.502573
The database contains a series of molecular causality statements where influence of upstream signaling entities (e.g proteins) to downstream signaling entities (e.g. proteins) is explicitly given, in a signed and directed manner. The CASCADE topology was built from a node-centric view and version 2.0 covers the following pathways:
- PI3K/AKT signaling pathway
- MAPK-signaling pathways (JNK, MAPK14, ERK)
- TGFBR-signaling pathway
- JAK-STAT signaling pathway
- WNT-CTNNB1 signaling pathway
- NFkB signaling pathway
These pathways are linked to prosurvival and antisurvival cell signaling (e.g. cyclin expression and caspase activation).
The cascade_to_sif.Rmd R code can be used to convert the SIGNOR data (.tsv) to a topology (.sif) file.
The example in the code re-creates the cascade_2.0.sif (CASCADE 2.0 version).
Eirini Tsirvouli, Barbara Niederdorfer, John Zobolas, Touré Vasundra, Åsmund Flobak, & Martin Kuiper. (2020, October 5). CASCADE - CAncer Signaling CAusality DatabasE (Version 3.0). Zenodo. http://doi.org/10.5281/zenodo.4066665
- CASCADE 1.0: [email protected]
- CASCADE 2.0: [email protected]
- CASCADE 3.0: [email protected]