A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles
Abstrak
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. HIGHLIGHTS A new gene expression profiling method, L1000, dramatically lowers cost The Connectivity Map database now includes 1.3 million publicly accessible L1000 perturbational profiles This expanded Connectivity Map facilitates discovery of small molecule mechanism of action and functional annotation of genetic variants The work establishes feasibility and utility of a truly comprehensive Connectivity Map
Penulis (56)
A. Subramanian
Rajiv Narayan
S. M. Corsello
David Peck
Ted E. Natoli
Xiaodong Lu
Joshua Gould
John F. Davis
Andrew A. Tubelli
Jacob K. Asiedu
D. Lahr
J. Hirschman
Zihan Liu
M. Donahue
Bina Julian
Mariya Khan
David Wadden
Ian Smith
Daniel Lam
A. Liberzon
Courtney Toder
Mukta Bagul
Marek Orzechowski
Oana M. Enache
F. Piccioni
Sarah Johnson
Nicholas J. Lyons
A. Berger
Alykhan F. Shamji
Angela N. Brooks
Anita Vrcic
Corey Flynn
Jacqueline Rosains
D. Takeda
R. Hu
Desiree Davison
J. Lamb
K. Ardlie
L. Hogstrom
Peyton Greenside
N. Gray
P. Clemons
S. Silver
Xiaoyun Wu
Wen-Ning Zhao
Willis Read-Button
Xiaohua Wu
S. Haggarty
L. Ronco
J. Boehm
S. Schreiber
John G Doench
Joshua A. Bittker
D. Root
Bang Wong
T. Golub
Akses Cepat
- Tahun Terbit
- 2017
- Bahasa
- en
- Total Sitasi
- 2820×
- Sumber Database
- Semantic Scholar
- DOI
- 10.1101/136168
- Akses
- Open Access ✓