ArticleCell2017
A Next Generation Connectivity Map: L1000 Platform and the First 1,000,000 Profiles.
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Article in Cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2,095 papers, 1 of them a synthesis that pooled it.
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2,095 citing papers in PubMed, 1 synthesis or guideline pooled it.
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2,035 more citing papers are in PubMed but not listed here.
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Authors and funding
56 authors.
Aravind SubramanianBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Rajiv NarayanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Steven M CorselloBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
David D PeckBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ted E NatoliBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xiaodong LuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joshua GouldBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
John F DavisBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Andrew A TubelliBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jacob K AsieduBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David L LahrBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jodi E HirschmanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Zihan LiuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Melanie DonahueBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bina JulianBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mariya KhanBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David WaddenBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Ian C SmithBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Daniel LamBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Arthur LiberzonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Courtney ToderBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Mukta BagulBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Marek OrzechowskiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Oana M EnacheBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Federica PiccioniBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Sarah A JohnsonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nicholas J LyonsBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Alice H BergerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Alykhan F ShamjiBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Angela N BrooksBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Anita VrcicBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Corey FlynnBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jacqueline RosainsBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David Y TakedaBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA; Harvard Medical School, Boston, MA 02115, USA.
Roger HuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Desiree DavisonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Justin LambBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Kristin ArdlieBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Larson HogstromBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Peyton GreensideBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Nathanael S GrayBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Cancer Biology, Dana-Farber Cancer Institute, Boston, MA 02215, USA.
Paul A ClemonsBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Serena SilverBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xiaoyun WuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Wen-Ning ZhaoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Willis Read-ButtonBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Xiaohua WuBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Stephen J HaggartyBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Department of Neurology, Massachusetts General Hospital, Boston, MA 02114, USA.
Lucienne V RoncoBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Jesse S BoehmBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Stuart L SchreiberBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Department of Chemistry and Chemical Biology, Harvard University, Cambridge, MA 02138, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA.
John G DoenchBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Joshua A BittkerBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
David E RootBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Bang WongBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA.
Todd R GolubBroad Institute of MIT and Harvard, Cambridge, MA 02142, USA; Harvard Medical School, Boston, MA 02115, USA; Howard Hughes Medical Institute, Chevy Chase, MD 20815, USA; Department of Pediatric Oncology, Dana-Farber Cancer Institute, Boston, MA 02215, USA. Electronic address: golub@broadinstitute.org.
Funding
Physician Scientist Training in Cancer ResearchT32CA009172 · NCI · DANA-FARBER CANCER INSTITUTE · PI Jennifer R Brown, James A. DeCaprio · 1985 to 2026
$17.1MDiscovering existing medicines that abrogate cellular responses to SARS CoV-2 infectionU54HL127366 · NHLBI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R. · 2014 to 2020
$14.3MLarge scale gene expression analysis of cellular statesU54HG006093 · NHGRI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., SUBRAMANIAN, ARAVIND · 2010 to 2013
$9.1MHarvard Clinical and Translational Science CenterKL2TR001100 · NCATS · HARVARD MEDICAL SCHOOL · PI NADLER, LEE MARSHALL · 2013 to 2017
$8.5MLINCS Data Coordination and Integration CenterU01HG008699 · NHGRI · BROAD INSTITUTE, INC. · PI GOLUB, TODD R., SUBRAMANIAN, ARAVIND · 2015 to 2019
$3.2MNCATS NIH HHS KL2 TR001100NCI NIH HHS T32 CA009172NHGRI NIH HHS U01 HG008699NHGRI NIH HHS U54 HG006093NHLBI NIH HHS U54 HL127366
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.
Indexed as
Cell Line, TumorDrug Resistance, NeoplasmGene Expression ProfilingHumansNeoplasmsOrgan SpecificityPharmaceutical PreparationsSequence Analysis, RNASmall Molecule LibrariesPharmaceutical PreparationsSmall Molecule Librarieschemical biologyFunctional genomicsgene expression profiling
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