title: Compound signature detection on LINCS L1000 big data.
abstract: 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.
authors.affiliation: School of Mathematical Sciences and LMAM, Peking University, Beijing 100871, China.
authors.forename: Chenglin
authors.initials: C
authors.lastname: Liu
authors.forename: Jing
authors.initials: J
authors.lastname: Su
authors.forename: Fei
authors.initials: F
authors.lastname: Yang
authors.forename: Kun
authors.initials: K
authors.lastname: Wei
authors.forename: Jinwen
authors.initials: J
authors.lastname: Ma
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Zhou
mesh_terms: D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics; D045744:Cell Line, Tumor; D019295:Computational Biology / Q000379:methods; D066264:Datasets as Topic; D055808:Drug Discovery / Q000379:methods; D004354:Drug Screening Assays, Antitumor; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D058977:Molecular Sequence Annotation; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D015203:Reproducibility of Results; D054852:Small Molecule Libraries; D059467:Transcriptome; D057188:Workflow
chemical_list: D047428:Protein Kinase Inhibitors; D034741:RNA, Small Interfering; D054852:Small Molecule Libraries