Connectivity Map
The Connectivity Map (CMap) is a groundbreaking genome-scale perturbation resource containing over 3 million gene expression profiles cataloging transcriptional responses to chemical, genetic, and disease perturbations across multiple cancer cell types. Developed by the Broad Institute as part of the NIH Library of Integrated Network-Based Cellular Signatures (LINCS) program, CMap addresses fundamental challenges in understanding protein function and small molecule mechanisms of action by creating a comprehensive catalog of cellular signatures representing systematic perturbation. The database employs the L1000 high-throughput gene expression assay, which directly measures ~978 landmark genes and computationally infers expression of ~11,350 additional genes using inference algorithms, providing a cost-effective reduced representation of the transcriptome. CMap contains signatures from approximately 5,000 small-molecule compounds, 3,000 genetic reagents including shRNAs, CRISPR knockdowns, and overexpression constructs, tested primarily across nine core cancer cell lines that include A375, A549, HA1E, HCC515, HT29, HEPG2, MCF7, PC3, and VCAP. The resource enables researchers to query with their own gene expression signatures to identify perturbagens that induce similar or opposing transcriptional responses, thereby discovering unexpected connections between diseases, drug mechanisms, and protein functions. CMap data is accessible through CLUE, a cloud-based unified environment providing user-friendly web applications including query tools, data browsers, metadata search, and visualization apps for exploring perturbation-driven gene expression patterns. The database supports diverse research applications including drug repurposing by identifying compounds with similar mechanisms, target identification by finding small molecules that mimic genetic perturbations, disease mechanism understanding by connecting disease signatures to perturbagen responses, and biomarker discovery through systematic analysis of transcriptional responses. While personalized support ended in July 2022, all data, tools, and extensive documentation through Connectopedia remain fully accessible, with over 1.5 million replicate-collapsed signatures and 3 million profiles available for download and programmatic access via Python libraries and APIs.
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