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Fish Connectivity Mapping II: An Upgraded Library of Expression Profiles and its Performance Evaluations
Citation:
Wang, R., D. Bencic, A. Biales, R. Flick, AND M. Hu. Fish Connectivity Mapping II: An Upgraded Library of Expression Profiles and its Performance Evaluations. SETAC North America 42nd Annual meeting, Portland, OR, November 14 - 18, 2021. https://doi.org/10.23645/epacomptox.17102465
Impact/Purpose:
Presentation to the SETAC North America 42nd Annual Meeting Nov 2021. Fish connectivity mapping represents a omics-based data-driven approach to integrate toxicogenomics data for assessing chemical toxicities, with applications in chemical grouping, endpoints read-across, diagnostics, and discovery of mechanisms of actions.
Description:
Connectivity mapping (Cmap) links conditions, either of chemical or biological nature, through their respectively associated multi-gene queries and whole transcriptome rank-ordered gene lists (ROGLs) organized as a library. Cmap leverages an entire such library for chemical grouping, read-across, diagnostics, and discovery of mechanisms of action (MOAs). The limited Cmap library created in a 2016 pilot study has been significantly upgraded to encompass hundreds more microarray studies of fathead minnow and zebrafish available from the NCBI GEO repository as of March 2021. Also included is a small but increasing RNA-seq collection from ongoing toxicogenomics research at the EPA. The library now contains over 8000 ROGLs based on more than 11,000 samples, representing 600-plus unique chemical or biological conditions. To evaluate the toxicological applications of this library and its performance, we constructed more than 1100 query sets from the same studies to interrogate the library computationally. Performance evaluation was conducted base on a dozen chemical class or biological conditions found in the query sets with each containing multiple independent studies targeting a common condition. They ranged from dioxins, polycyclic aromatic hydrocarbons, estrogens, pesticides, to field samples. A pair of mapped query-ROGL was considered positive when both were associated with the same or similar chemical class/biological condition but derived from two independent studies. For each such condition, queries were expected to recover above a minimum (based on the number of selected studies of the same tissue/organ type) but below a maximum (all the selected studies assumed to have the same tissue/organ type) number of target ROGLs since tissue/organ type is critical to gene expression yet was often unknown. Overall, an average of 257% of minimum expected mappings was recovered successfully among the top five hits of individual ROGL collections. Also discovered were many other unexpected but positive ROGL targets, the matching queries of which were either not constructable from their original studies or not included in analysis. These findings have further demonstrated the utilities of Cmap in toxicology. This upgraded library marks another important step towards a better integration of toxicogenomics data in the future. As its coverage of chemicals and biology grows, so will its power of various applications.
URLs/Downloads:
DOI: Fish Connectivity Mapping II: An Upgraded Library of Expression Profiles and its Performance Evaluations
CMAP10252021SETAC.PDF (PDF, NA pp, 1133.982 KB, about PDF)