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High Throughput Transcriptomics: From screening to pathways
Shah, I. High Throughput Transcriptomics: From screening to pathways. SOT, San Antonio, TX, March 11 - 15, 2018.
High-throughput screening (HTS) assays are an important component of chemical safety evaluation programs carried out by a number of organizations. However, it is recognized that the assays do not sufficiently cover all potentially important pathways. In the last few years adaptation of gene expression profiling to high throughput formats is increasingly considered an attractive alternative to individual assays due to lower costs and the ability to measure essentially all pathways simultaneously.
The EPA ToxCast effort has screened thousands of chemicals across hundreds of high-throughput in vitro screening assays. The project is now leveraging high-throughput transcriptomic (HTTr) technologies to substantially expand its coverage of biological pathways. The first HTTr screen has measured the expression of 19,290 genes in MCF7 cells for more than 1,000 chemicals in concentration response format. We have developed a computational strategy to interpret the HTTr data in terms of pathway perturbations, the specificity of pathway perturbations and associated points of departure. A strategy for integrating these new transcriptomic technologies into high throughput toxicity testing will be presented and the challenges discussed. We believe HTTr technologies can be deployed in a tiered fashion to complement the existing suite of high-throughput in vitro screening assays to realize the vision of Toxicity Testing in the 21st Century.
URLs/Downloads:SHAH-HTTR-SLIDES-SOT-2018-V1C.PDF (PDF,NA pp, 4134.085 KB, about PDF)
SOT 2018 SESSION PROPOSAL ON TRANSCRIPT PROFILING V3 05_02_17.PDF (PDF,NA pp, 33.181 KB, about PDF)