The Library of Integrated Network-based Cellular Signatures (LINCS) L1000 big 
data provide gene expression profiles induced by over 10 000 compounds, shRNAs, 
and kinase inhibitors using the L1000 platform. We developed csNMF, a systematic 
compound signature discovery pipeline covering from raw L1000 data processing to 
drug screening and mechanism generation. The csNMF pipeline demonstrated better 
performance than the original L1000 pipeline. The discovered compound signatures 
of breast cancer were consistent with the LINCS KINOMEscan data and were 
clinically relevant. The csNMF pipeline provided a novel and complete tool to 
expedite signature-based drug discovery leveraging the LINCS L1000 resources.