From: Knowledge graph analytics platform with LINCS and IDG for Parkinson's disease target illumination
LINCS key concepts | IDG key concepts |
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L1000: Broad Institute microarray platform and LINCS project involving landmark genes | Target: Drug targets normally defined as human proteins or equivalently protein coding genes |
Landmark Gene: approximately 1000 genes representing the full human genome, from which a maximum set of gene responses can be inferred | Mechanism of action: Known, published, biochemical mechanism of pharmacological effect |
Cell Lines: Primary cells and human patient induced pluripotent stem cells (iPSCs) representing diverse tissues and disease states (including ‘healthy’ controls) | Disease: Working definition is anything which could be the clinical indication for a drug |
Perturbagen: A perturbagen may be chemical (drug-like), biologics, or genetic | Ligand: Small molecule with known or hypothesized relationship with one or more targets |
Signatures: Various assays (transcriptomics, proteomics, or image analysis) are integrated together to identify patterns of common networks and cellular responses leading to predictive mechanistic interpretations | Target Development Level (TDL): Simple measure of illumination: Tdark, Tbio, Tchem and Tclin |
Target Importance and Novelty: Bibliometric measures from TIN-X for target prioritization | |
LINCS-IDG semantic linkage | |
LINCS centers utilize in-depth gene and protein expression assays to generate signatures directly mappable to IDG protein targets. Disease and phenotype ontology mapping is a community challenge with useful, working solutions such as UMLS [8]. LINCS perturbagens include rigorously defined chemical entities and small molecule drugs included in IDG resource DrugCentral. Therefore, LINCS’s vast number of human cell lines and experimental chemical perturbation datasets, combined with IDG’s protein targets (gene and protein IDs) and DrugCentral active pharmaceutical ingredients (drug compounds) databases, provide a tightly integrated combination resource for drug target discovery |