Subramanian A, Narayan R, Corsello SM, Peck DD, Natoli TE, Lu X, Gould J, Davis JF, Tubelli AA, Asiedu JK, et al. A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles. Cell. 2017;171:1437–1452 e17.
NOTES
Subramanian, AravindNarayan, RajivCorsello, Steven MPeck, David DNatoli, Ted ELu, XiaodongGould, JoshuaDavis, John FTubelli, Andrew AAsiedu, Jacob KLahr, David LHirschman, Jodi ELiu, ZihanDonahue, MelanieJulian, BinaKhan, MariyaWadden, DavidSmith, Ian CLam, DanielLiberzon, ArthurToder, CourtneyBagul, MuktaOrzechowski, MarekEnache, Oana MPiccioni, FedericaJohnson, Sarah ALyons, Nicholas JBerger, Alice HShamji, Alykhan FBrooks, Angela NVrcic, AnitaFlynn, CoreyRosains, JacquelineTakeda, David YHu, RogerDavison, DesireeLamb, JustinArdlie, KristinHogstrom, LarsonGreenside, PeytonGray, Nathanael SClemons, Paul ASilver, SerenaWu, XiaoyunZhao, Wen-NingRead-Button, WillisWu, XiaohuaHaggarty, Stephen JRonco, Lucienne VBoehm, Jesse SSchreiber, Stuart LDoench, John GBittker, Joshua ARoot, David EWong, BangGolub, Todd RengKL2 TR001100/TR/NCATS NIH HHS/U54 HG006093/HG/NHGRI NIH HHS/T32 CA009172/CA/NCI NIH HHS/U01 HG008699/HG/NHGRI NIH HHS/U54 HL127366/HL/NHLBI NIH HHS/Cell. 2017 Nov 30;171(6):1437-1452.e17. doi: 10.1016/j.cell.2017.10.049.
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.
Last updated on 02/17/2021