You are here

Cell Syst DOI:10.1016/j.cels.2018.03.012

A Library of Phosphoproteomic and Chromatin Signatures for Characterizing Cellular Responses to Drug Perturbations.

Publication TypeJournal Article
Year of Publication2018
AuthorsLitichevskiy, L, Peckner, R, Abelin, JG, Asiedu, JK, Creech, AL, Davis, JF, Davison, D, Dunning, CM, Egertson, JD, Egri, S, Gould, J, Ko, T, Johnson, SA, Lahr, DL, Lam, D, Liu, Z, Lyons, NJ, Lu, X, MacLean, BX, Mungenast, AE, Officer, A, Natoli, TE, Papanastasiou, M, Patel, J, Sharma, V, Toder, C, Tubelli, AA, Young, JZ, Carr, SA, Golub, TR, Subramanian, A, MacCoss, MJ, Tsai, L-H, Jaffe, JD
JournalCell Syst
Volume6
Issue4
Pages424-443.e7
Date Published2018 Apr 25
ISSN2405-4712
Abstract

Although the value of proteomics has been demonstrated, cost and scale are typically prohibitive, and gene expression profiling remains dominant for characterizing cellular responses to perturbations. However, high-throughput sentinel assays provide an opportunity for proteomics to contribute at a meaningful scale. We present a systematic library resource (90 drugs × 6 cell lines) of proteomic signatures that measure changes in the reduced-representation phosphoproteome (P100) and changes in epigenetic marks on histones (GCP). A majority of these drugs elicited reproducible signatures, but notable cell line- and assay-specific differences were observed. Using the "connectivity" framework, we compared signatures across cell types and integrated data across assays, including a transcriptional assay (L1000). Consistent connectivity among cell types revealed cellular responses that transcended lineage, and consistent connectivity among assays revealed unexpected associations between drugs. We further leveraged the resource against public data to formulate hypotheses for treatment of multiple myeloma and acute lymphocytic leukemia. This resource is publicly available at https://clue.io/proteomics.

DOI10.1016/j.cels.2018.03.012
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29655704?dopt=Abstract

Alternate JournalCell Syst
PubMed ID29655704
Grant ListU54 HG008097 / HG / NHGRI NIH HHS / United States
U54 HL127366 / HL / NHLBI NIH HHS / United States