title: Transcriptional Characterization of Compounds: Lessons Learned from the Public LINCS Data.
abstract: The NIH-funded LINCS program has been initiated to generate a library of integrated, network-based, cellular signatures (LINCS). A novel high-throughput gene-expression profiling assay known as L1000 was the main technology used to generate more than a million transcriptional profiles. The profiles are based on the treatment of 14 cell lines with one of many perturbation agents of interest at a single concentration for 6 and 24 hours duration. In this study, we focus on the chemical compound treatments within the LINCS data set. The experimental variables available include number of replicates, cell lines, and time points. Our study reveals that compound characterization based on three cell lines at two time points results in more genes being affected than six cell lines at a single time point. Based on the available LINCS data, we conclude that the most optimal experimental design to characterize a large set of compounds is to test them in duplicate in three different cell lines. Our conclusions are constrained by the fact that the compounds were profiled at a single, relative high concentration, and the longer time point is likely to result in phenotypic rather than mechanistic effects being recorded.
authors.affiliation: 1 Department of Discovery Sciences, Janssen R&D , Beerse, Belgium .
authors.forename: Hans
authors.initials: H
authors.lastname: De Wolf
authors.affiliation: 1 Department of Discovery Sciences, Janssen R&D , Beerse, Belgium .
authors.forename: An
authors.initials: A
authors.lastname: De Bondt
authors.affiliation: 2 Open Analytics NV , Antwerp, Belgium .
authors.forename: Heather
authors.initials: H
authors.lastname: Turner
authors.affiliation: 1 Department of Discovery Sciences, Janssen R&D , Beerse, Belgium .
authors.forename: Hinrich W H
authors.initials: HW
authors.lastname: Göhlmann
mesh_terms: D000072283:A549 Cells; D000970:Antineoplastic Agents / Q000494:pharmacology; D030541:Databases, Genetic; D020869:Gene Expression Profiling / Q000379:methods*; D015723:Gene Library; D019073:HT29 Cells; D056945:Hep G2 Cells; D006801:Humans; D061986:MCF-7 Cells; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D059467:Transcriptome / Q000187:drug effects / Q000235:genetics*
chemical_list: D000970:Antineoplastic Agents