Table 5.
Resources for the mechanism and mode of action of chemical and genetic perturbations
| Resource | Genomics target | Number of perturbations or compound–gene associations | Number of cell lines/tumors | Description | Link | References |
|---|---|---|---|---|---|---|
| Mechanisms of action | ||||||
| ChEMBL | Proteins | ~15 Million activities between ~1.7 million compounds and ~11 500 target genes (version 23) | The largest data resource with comprehensive search interface of associations between ligands and protein targets curated from ~30 data sources | https://www.ebi.ac.uk/chembl/ | [114–116] | |
| PharmGKB (Pharmacogenetics Knowledge Base) | Gene alterations; PD and PK pathways | ~20 000 variant–drug pairs of 641 drugs | Curation of variant—PD/PK pathways—drug with clinical annotations | https://www.pharmgkb.org/ | [117] | |
| CTRP (Cancer Therapeutics Response Portal) | GEX | 481 compounds | 860 cell lines | Correlation between basal expression levels of ~19 000 genes and AUC of 481 compounds across cell lines | https://portals.broadinstitute.org/ctrp/ | [118–120] |
| OncoKB | Gene alterations | 86 drugs to ~3900 variants on 477 genes | 60 cancer types | Curated classification of level-1 (FDA-approved) to level-4 (biologically proven) drug targeting variants | http://oncokb.org | [122] |
| Modes of action | ||||||
| Library of Integrated Network-Based Cellular Signatures (LINCS) | GEX (L1000 array: ~1000 assayed and ~11 000 inferred genes); proteins (P100 array: ~100 phosphorylated peptides) | Phase I data (completed): ~20 000 chemical and ~8000 genetic perturbations with several doses and time points | Phase I: 76 cell lines Phase II: 41 Union: 98 | ~1 300 000 (Phase I) and ~350 000 (Phase II) basal and post-treatment GEX profiles normalized to ~476 000 and ~118 000 gene signatures | Cloud-based analysis platform: https://clue.io/ Data Portal: http://lincsportal.ccs.miami.edu/dcic-portal/ Phase I data also available at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE92742 Phase II data also available at: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE70138 Proteomic data: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE101406 MATLAB, Python, R tools for data processing [123]: https://github.com/cmap | [91] |
| Phase II (version Mar 2017): ~1800 chemical perturbations with several doses and time points | ||||||
| Molecular Signatures Database (MSigDB) – C2.CGP collection (Chemical and Genetic Perturbations) | GEX (significantly changed genes) | ~3400 chemical and genetic perturbations | Curated gene sets of genes changed with chemical and genetic perturbations | http://software.broadinstitute.org/gsea/msigdb/index.jsp | [52–54] | |
AUC, area under the dose response curve; GEX, gene expression; PD, pharmacodynamics; PK, pharmacokinetics.