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A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles

Subramanian, Aravind and Narayan, Rajiv and Corsello, Steven M. and Peck, David D. and Natoli, Ted E. and Lu, Xiaodong and Gould, Joshua and Davis, John F. and Tubelli, Andrew A. and Asiedu, Jacob K. and Lahr, David L. and Hirschman, Jodi E. and Liu, Zihan and Donahue, Melanie and Julian, Bina and Khan, Mariya and Wadden, David and Smith, Ian and Lam, Daniel and Liberzon, Arthur and Toder, Courtney and Bagul, Mukta and Orzechowski, Marek and Enache, Oana M. and Piccioni, Frederica and Berger, Alice H. and Shamji, Alykhan and Brooks, Angela N. and Vrcic, Anita and Flynn, Corey and Rosains, Jacqueline and Takeda, David and Davison, Desiree and Lamb, Justin and Ardlie, Kristin and Hogstrom, Larson and Gray, Nathanael S. and Clemons, Paul A. and Silver, Serena and Wu, Xiaoyun and Zhao, Wen-Ning and Read-Button, Willis and Wu, Xiaohua and Haggarty, Stephen J. and Ronco, Lucienne V. and Boehm, Jesse S. and Schreiber, Stuart L. and Doench, John G. and Bittker, Joshua A. and Root, David E. and Wong, Bang and Golub, Todd R. (2017) A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles. Biorxiv.

Abstract

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.

Item Type: Article
Date Deposited: 13 Sep 2017 00:45
Last Modified: 13 Sep 2017 00:45
URI: https://oak.novartis.com/id/eprint/34100

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