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High content screening of ToxCast compounds using Vala Sciences’ complex cell culturing systems (SOT)
Citation:
Connors, K., D. Filer, N. Sipes, R. Judson, K. Houck, AND M. Martin. High content screening of ToxCast compounds using Vala Sciences’ complex cell culturing systems (SOT). Presented at SOT Annual Meeting, San Deigo, CA, March 22 - 26, 2015. https://doi.org/10.23645/epacomptox.5178847
Impact/Purpose:
Present poster at SOT annual meeting in San Diego, CA on March 24, 2015
Description:
US EPA’s ToxCast research program evaluates bioactivity for thousands of chemicals utilizing high-throughput screening assays to inform chemical testing decisions. Vala Sciences provides high content, multiplexed assays that utilize quantitative cell-based digital image analysis. Twelve assays, with a wide variety of early response targets, were selected for analysis in ToxCast and initially tested across the 311 ToxCast Phase I chemicals. Targets include those important in embryonic stem cell differentiation, neuronal function, pancreatic beta cell differentiation, germ layer proliferation, adipogenesis, adipocyte lipolysis, hepatic steatosis, and junctional proteins critical to developmental angiogenic processes and tumor progression. Due to the diversity of assays and the large number of cellular imaging features from each assay, a systematic selection process was used to select assay endpoints that were statistically robust with strictly standardized mean differences (SSMD) of β ≥ 5. Using the ToxCast Data Analysis Pipeline, six-point concentration-response modeling and activity calling was performed. Preliminary analysis identified 31-189 unique chemicals that were classified as active. Specifically, 189 chemicals were active in the junctional protein assays while 110 chemicals affected neuronal endpoints. Early response targets in this data set provide toxicological and mechanistic insight to complement other ToxCast assays leading to stronger predictive toxicity models. Collectively, these results add important data to ToxCast that will help identify and prioritize possible developmental toxicants, endocrine disruptors, liver toxicants, and carcinogens to inform target testing strategies. This abstract does not necessarily represent U.S. EPA policy.
URLs/Downloads:
DOI: High content screening of ToxCast compounds using Vala Sciences’ complex cell culturing systems (SOT)