Author:
Lim Nathaniel,Pavlidis Paul
Abstract
AbstractThe Connectivity Map (CMap) is a popular resource designed for data-driven drug repositioning using a large transcriptomic compendium. However, evaluations of its performance are limited. We used two iterations of CMap (CMap 1 and 2) to assess their comparability and reliability. We queried CMap 2 with CMap 1-derived signatures, expecting CMap 2 would highly prioritize the queried compounds; the success rate was 17%. Analysis of previously published prioritizations yielded similar results. Low recall is caused by low differential expression (DE) reproducibility both between CMaps and within each CMap. DE strength was predictive of reproducibility, and is influenced by compound concentration and cell-line responsiveness. Reproducibility of CMap 2 sample expression levels was also lower than expected. We attempted to identify the “better” CMap by comparison with a third dataset, but they were mutually discordant. Our findings have implications for CMap usage and we suggest steps for investigators to limit false positives.
Funder
University of British Columbia
National Institutes of Health
Natural Sciences and Engineering Research Council of Canada
Publisher
Springer Science and Business Media LLC
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