ArticlePloS one2018
A hybrid gene selection approach to create the S1500+ targeted gene sets for use in high-throughput transcriptomics.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 160 citations in OpenAlex.
- Knowledge-Driven Approaches to Create the MTox700+ Metabolite Panel for Predicting Toxicity.Toxicological sciences : an official journal of the Society of Toxicology · 2022Pooled it
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- Transplatformer: translating toxicogenomic profiles between generations of platforms.BMC bioinformatics · 2026Article
- A systems-level integration of liver-kidney transcriptomics and genome-scale metabolic models reveals organ-specific injury mechanisms.Frontiers in toxicology · 2026Article
- Nucleophosmin 1 induction is an early event in a Phenobarbital induced proliferation response in rat but not human liver 3D microtissues.Toxicology reports · 2025Article
- Comparison of whole transcriptome and targeted RNA sequencing for ecological high-throughput transcriptomics.Regulatory toxicology and pharmacology : RTP · 2025Article
- Fetal response to maternal exposures of environmental chemicals: Utility of a four-cell human feto-maternal interface organ-on-chip.Chemico-biological interactions · 2025Article
- Fenofibrate differentially activates PPARα-mediated lipid metabolism in rat kidney and liver.Scientific reports · 2025Article
- AIVIVE: a novel AI framework for enhanced in vitro to in vivo extrapolation (IVIVE) of toxicogenomics data.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Identification of four mechanisms of toxicity for per- and polyfluoroalkyl substances through transcriptomic profiling in human liver spheroids exposed to 24 PFAS.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Comprehensive analysis of high-throughput transcriptomics to distinguish drug-induced liver injury (DILI) phenotypes.Archives of toxicology · 2025Review
- Article
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- A workflow for human health hazard evaluation using transcriptomic data and Key Characteristics-based gene sets.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Comparative analysis of Caco-2 cells and human jejunal and duodenal enteroid-derived cells in gel- and membrane-based barrier models of intestinal permeability.Toxicological sciences : an official journal of the Society of Toxicology · 2025Article
- Comparative Analysis of Proximal Tubule Cell Sources for In Vitro Studies of Renal Proximal Tubule Toxicity.Biomedicines · 2025Article
- Unraveling Human Hepatocellular Responses to PFAS and Aqueous Film-Forming Foams (AFFFs) for Molecular Hazard Prioritization and In Vivo Translation.Environmental science & technology · 2025Article
- Bioinformatic workflows for deriving transcriptomic points of departure: current status, data gaps, and research priorities.Toxicological sciences : an official journal of the Society of Toxicology · 2025Review
- Progress in toxicogenomics to protect human health.Nature reviews. Genetics · 2025Review
- Comparative analysis of the physiological and transport functions of various sources of renal proximal tubule cells under static and fluidic conditions in PhysioMimix T12 platform.Drug metabolism and disposition: the biological fate of chemicals · 2025Article
27 more citing papers are in PubMed but not listed here.
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Authors and funding
15 authors at 4 institutions in 1 country.
Funding
Abstract
Changes in gene expression can help reveal the mechanisms of disease processes and the mode of action for toxicities and adverse effects on cellular responses induced by exposures to chemicals, drugs and environment agents. The U.S. Tox21 Federal collaboration, which currently quantifies the biological effects of nearly 10,000 chemicals via quantitative high-throughput screening(qHTS) in in vitro model systems, is now making an effort to incorporate gene expression profiling into the existing battery of assays. Whole transcriptome analyses performed on large numbers of samples using microarrays or RNA-Seq is currently cost-prohibitive. Accordingly, the Tox21 Program is pursuing a high-throughput transcriptomics (HTT) method that focuses on the targeted detection of gene expression for a carefully selected subset of the transcriptome that potentially can reduce the cost by a factor of 10-fold, allowing for the analysis of larger numbers of samples. To identify the optimal transcriptome subset, genes were sought that are (1) representative of the highly diverse biological space, (2) capable of serving as a proxy for expression changes in unmeasured genes, and (3) sufficient to provide coverage of well described biological pathways. A hybrid method for gene selection is presented herein that combines data-driven and knowledge-driven concepts into one cohesive method. Our approach is modular, applicable to any species, and facilitates a robust, quantitative evaluation of performance. In particular, we were able to perform gene selection such that the resulting set of "sentinel genes" adequately represents all known canonical pathways from Molecular Signature Database (MSigDB v4.0) and can be used to infer expression changes for the remainder of the transcriptome. The resulting computational model allowed us to choose a purely data-driven subset of 1500 sentinel genes, referred to as the S1500 set, which was then augmented using a knowledge-driven selection of additional genes to create the final S1500+ gene set. Our results indicate that the sentinel genes selected can be used to accurately predict pathway perturbations and biological relationships for samples under study.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.