%0 Journal Article %A Aravind Subramanian %A Rajiv Narayan %A Steven M. Corsello %A David D. Peck %A Ted E. Natoli %A Xiaodong Lu %A Joshua Gould %A John F. Davis %A Andrew A. Tubelli %A Jacob K. Asiedu %A David L. Lahr %A Jodi E. Hirschman %A Zihan Liu %A Melanie Donahue %A Bina Julian %A Mariya Khan %A David Wadden %A Ian Smith %A Daniel Lam %A Arthur Liberzon %A Courtney Toder %A Mukta Bagul %A Marek Orzechowski %A Oana M. Enache %A Federica Piccioni %A Alice H. Berger %A Alykhan Shamji %A Angela N. Brooks %A Anita Vrcic %A Corey Flynn %A Jacqueline Rosains %A David Takeda %A Desiree Davison %A Justin Lamb %A Kristin Ardlie %A Larson Hogstrom %A Nathanael S. Gray %A Paul A. Clemons %A Serena Silver %A Xiaoyun Wu %A Wen-Ning Zhao %A Willis Read-Button %A Xiaohua Wu %A Stephen J. Haggarty %A Lucienne V. Ronco %A Jesse S. Boehm %A Stuart L. Schreiber %A John G. Doench %A Joshua A. Bittker %A David E. Root %A Bang Wong %A Todd R. Golub %T A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles %D 2017 %R 10.1101/136168 %J bioRxiv %P 136168 %X We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io.HIGHLIGHTSA new gene expression profiling method, L1000, dramatically lowers costThe Connectivity Map database now includes 1.3 million publicly accessible L1000 perturbational profilesThis expanded Connectivity Map facilitates discovery of small molecule mechanism of action and functional annotation of genetic variantsThe work establishes feasibility and utility of a truly comprehensive Connectivity Map %U https://www.biorxiv.org/content/biorxiv/early/2017/05/10/136168.full.pdf