Target Affinity Spectrum (TAS) vectors for compounds in the HMS LINCS small molecule library. - Dataset (ID:20000)

HMS Dataset ID: 20000
Dataset Title: Target Affinity Spectrum (TAS) vectors for compounds in the HMS LINCS small molecule library.
Screening Lab Investigator: Nienke Moret
Screening Principal Investigator: Peter K. Sorger
Assay Description: The target affinity spectrum (TAS) is a vector of binding assertions based on dose-response affinity constants, one-dose percent inhibition data and manual literature curation.
Assay Protocol: To compare compounds based on all known targets and known non-targets, we sought a means to summarize all available target data on a compound, including dose-response data, profiling data and curated annotations from the literature (e.g. “drug X was found to not inhibit ..." or "was equipotent for ..."). The resulting Target Affinity Spectrum (TAS) vectors summarize binding information from multiple assay formats weighted for the degree of evidence for high affinity binding and also for non-binding (Kd > 10 µM). TAS vectors contain several best-guess weighting parameters and are therefore less precise than selectivity scores, but they provide a more complete picture of available data. For the LINCS library, TAS vectors varied in length from a median of 10 features for probe compounds (range 1-394) and 15 for approved drugs (range 1-420), (Wilcoxon rank-sum test p=0.07). In no cases did a TAS include assertions for all 545 human kinases, let alone for all ~3000 members of the druggable genome, which illustrates the sparseness of target annotation. TAS similarities for all compound pairs were calculated using a weighted Jaccard similarity metric. We found that TAS similarity was robust to at least 20% random variation in user-assigned parameters
Assay Protocol Reference: Moret, N., Clark, N., Hafner, M., Wang, Y., Lounkine, E., Medvedovic, M., Wang, J., Gray, N., Jenkins, J., and Sorger, P. (2019). Cheminformatics tools for analyzing and designing optimized small molecule libraries. CellChemBio. In press.
HMS Dataset Type: Analysis
Usage Message: The original dataset #20000 (LINCS Compound Protein Targets and Concentrations) with kinase inhibitor target information has been replaced with Target Affinity Spectrum binding information for small molecules in the HMS-LINCS database (March 2019).
Date Publicly Available: 2019-03-29
Most Recent Update: 2019-03-29