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

Cell
Authors
Keywords
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.

Year of Publication
2017
Journal
Cell
Volume
171
Issue
6
Pages
1437-1452.e17
Date Published
2017 Nov 30
ISSN
1097-4172
DOI
10.1016/j.cell.2017.10.049
PubMed ID
29195078
PubMed Central ID
PMC5990023
Links
Grant list
KL2 TR001100 / TR / NCATS NIH HHS / United States
U54 HG006093 / HG / NHGRI NIH HHS / United States
T32 CA009172 / CA / NCI NIH HHS / United States
U01 HG008699 / HG / NHGRI NIH HHS / United States
U54 HL127366 / HL / NHLBI NIH HHS / United States