ArticleProceedings of the National Academy of Sciences of the United States of America2007
Blood gene expression signatures predict exposure levels.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 120 citations in OpenAlex.
- Gene expression profiles in peripheral blood mononuclear cells of Chinese nickel refinery workers with high exposures to nickel and control subjects.Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology · 2013Trial
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- Blood toxicogenomics reveals potential biomarkers for management of idiosyncratic drug-induced liver injury.Frontiers in genetics · 2025Article
- SIRT2 Promotes HBV Transcription and Replication by Targeting Transcription Factor p53 to Increase the Activities of HBV Enhancers and Promoters.Frontiers in microbiology · 2022Article
- Multi-Walled Carbon Nanotube-Induced Gene Expression Biomarkers for Medical and Occupational Surveillance.International journal of molecular sciences · 2019Article
- A cross-talk between blood-cell neuroplasticity-related genes and environmental enrichment in working dogs.Scientific reports · 2019Article
- Article
- Transcriptomics in toxicology.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2017Review
- Sex-specific variation in signaling pathways and gene expression patterns in human leukocytes in response to endotoxin and exercise.Journal of neuroinflammation · 2016Article
- Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen.Clinical pharmacology and therapeutics · 2016Article
- Adaptation to acetaminophen exposure elicits major changes in expression and distribution of the hepatic proteome.Scientific reports · 2015Article
- Technical guide for applications of gene expression profiling in human health risk assessment of environmental chemicals.Regulatory toxicology and pharmacology : RTP · 2015Article
- Multi-walled carbon nanotube-induced gene expression in vitro: concordance with in vivo studies.Toxicology · 2015Article
- Toxicogenomics profiling of bone marrow from rats treated with topotecan in combination with oxaliplatin: a mechanistic strategy to inform combination toxicity.Frontiers in genetics · 2015Article
- Pathogenesis of idiosyncratic drug-induced liver injury and clinical perspectives.Gastroenterology · 2014Review
- Quantitative liver-specific protein fingerprint in blood: a signature for hepatotoxicity.Theranostics · 2014Article
- Blood transcriptomics: applications in toxicology.Journal of applied toxicology : JAT · 2013Review
- Transcriptomics analysis of lungs and peripheral blood of crystalline silica-exposed rats.Inhalation toxicology · 2012Article
- Identification and characterization of adverse effects in 21st century toxicology.Toxicological sciences : an official journal of the Society of Toxicology · 2012Article
- New perspectives for in vitro risk assessment of multiwalled carbon nanotubes: application of coculture and bioinformatics.Journal of toxicology and environmental health. Part B, Critical reviews · 2012Article
Corrections and comments
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Authors and funding
15 authors at 6 institutions in 1 country.
Funding
Abstract
To respond to potential adverse exposures properly, health care providers need accurate indicators of exposure levels. The indicators are particularly important in the case of acetaminophen (APAP) intoxication, the leading cause of liver failure in the U.S. We hypothesized that gene expression patterns derived from blood cells would provide useful indicators of acute exposure levels. To test this hypothesis, we used a blood gene expression data set from rats exposed to APAP to train classifiers in two prediction algorithms and to extract patterns for prediction using a profiling algorithm. Prediction accuracy was tested on a blinded, independent rat blood test data set and ranged from 88.9% to 95.8%. Genomic markers outperformed predictions based on traditional clinical parameters. The expression profiles of the predictor genes from the patterns extracted from the blood exhibited remarkable (97% accuracy) transtissue APAP exposure prediction when liver gene expression data were used as a test set. Analysis of human samples revealed separation of APAP-intoxicated patients from control individuals based on blood expression levels of human orthologs of the rat discriminatory genes. The major biological signal in the discriminating genes was activation of an inflammatory response after exposure to toxic doses of APAP. These results support the hypothesis that gene expression data from peripheral blood cells can provide valuable information about exposure levels, well before liver damage is detected by classical parameters. It also supports the potential use of genomic markers in the blood as surrogates for clinical markers of potential acute liver damage.
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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.