Phospho-proteomic Profiling Dataset of Chemical Perturbations in Multiple Biological Backgrounds

The Library of Integrated Network-based Cellular Signatures (LINCS) Program aims to create a network-based understanding of biology by cataloging changes in gene expression and other cellular processes that occur when cells are exposed to a variety of perturbing agents. The goal of this project is to test the hypothesis that modulation of phosphorylation-mediated signaling events in response to perturbations can establish new cellular states by altering their epigenetic landscape. We have performed mass spectrometry (MS)-based proteomic assays that target quantitative readouts of phospho-signaling and chromatin modifications in cellular models, following perturbation by compounds with varying mechanisms of action. We have employed 128 compounds and treated 5 cancer and 2 neuronal cell lines. The resulting data collected and tools created have been contributed to the LINCS program for the purpose of making connections among disparate perturbations through phosphoproteomics and chromatin modification signatures in concert with other available data types. The data is publicly available on PanoramaPublic and can be queried using Clue (Broad Institute). Analysis of our data will inform novel therapeutic opportunities and synergies, as dysregulation of phospho-signaling and epigenetic systems are two of the most common molecular etiologies identified in a growing number of diseases.