A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles

被引：2124

作者：

Subramanian, Aravind ^{[1
]}

Narayan, Rajiv ^{[1
]}

Corsello, Steven M. ^{[1
,2
,3
]}

Peck, David D. ^{[1
]}

Natoli, Ted E. ^{[1
]}

Lu, Xiaodong ^{[1
]}

Gould, Joshua ^{[1
]}

Davis, John F. ^{[1
]}

Tubelli, Andrew A. ^{[1
]}

Asiedu, Jacob K. ^{[1
]}

Lahr, David L. ^{[1
]}

Hirschman, Jodi E. ^{[1
]}

Liu, Zihan ^{[1
]}

Donahue, Melanie ^{[1
]}

Julian, Bina ^{[1
]}

Khan, Mariya ^{[1
]}

Wadden, David ^{[1
]}

Smith, Ian C. ^{[1
]}

Lam, Daniel ^{[1
]}

Liberzon, Arthur ^{[1
]}

Toder, Courtney ^{[1
]}

Bagul, Mukta ^{[1
]}

Orzechowski, Marek ^{[1
]}

Enache, Oana M. ^{[1
]}

Piccioni, Federica ^{[1
]}

Johnson, Sarah A. ^{[1
]}

Lyons, Nicholas J. ^{[1
]}

Berger, Alice H. ^{[1
,2
,3
,9
]}

Shamji, Alykhan F. ^{[1
]}

Brooks, Angela N. ^{[1
,2
,3
,10
]}

Vrcic, Anita ^{[1
]}

Flynn, Corey ^{[1
]}

Rosains, Jacqueline ^{[1
,11
]}

Takeda, David Y. ^{[1
,2
,3
]}

Hu, Roger ^{[1
]}

Davison, Desiree ^{[1
]}

Lamb, Justin ^{[1
,12
]}

Ardlie, Kristin ^{[1
]}

Hogstrom, Larson ^{[1
]}

Greenside, Peyton ^{[1
,14
]}

Gray, Nathanael S. ^{[1
,3
,4
]}

Clemons, Paul A. ^{[1
]}

Silver, Serena ^{[1
]}

Wu, Xiaoyun ^{[1
]}

Zhao, Wen-Ning ^{[1
,3
,5
]}

Read-Button, Willis ^{[1
,12
]}

Wu, Xiaohua ^{[1
]}

Haggarty, Stephen J. ^{[1
,3
,5
]}

Ronco, Lucienne V. ^{[1
,13
]}

Boehm, Jesse S. ^{[1
]}

机构：

[1] Broad Inst MIT & Harvard, Cambridge, MA 02142 USA

[2] Dana Farber Canc Inst, Dept Med Oncol, Boston, MA 02215 USA

[3] Harvard Med Sch, Boston, MA 02115 USA

[4] Dana Farber Canc Inst, Dept Canc Biol, Boston, MA 02215 USA

[5] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[6] Harvard Univ, Dept Chem & Chem Biol, Cambridge, MA 02138 USA

[7] Howard Hughes Med Inst, Chevy Chase, MD 20815 USA

[8] Dana Farber Canc Inst, Dept Pediat Oncol, Boston, MA 02215 USA

[9] Univ Washington, Seattle, WA 98195 USA

[10] Univ Calif Santa Cruz, Santa Cruz, CA 95064 USA

[11] Seven Bridges Genom, Cambridge, MA 02142 USA

[12] Genometry, Cambridge, MA 02139 USA

[13] Fulcrum Therapeut, Cambridge, MA 02139 USA

[14] Stanford Univ, Palo Alto, CA 94305 USA

来源：

CELL | 2017年 / 171卷 / 06期

关键词：

GENE-EXPRESSION; ACQUIRED-RESISTANCE; CANCER; INHIBITION; DISCOVERY; DEGRADATION; PHA-793887; SIGNATURE; TRICLOSAN; EFFICACY;

D O I：

10.1016/j.cell.2017.10.049

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：1437 / +

页数：33

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