Completed the collaborative support of investigators' research: 1) We employed bioinformatics strategies to analyze genomic data. 2) We used our custom Extracting Patterns and Identifying co-expressed Genes (EPIG) analysis tool to find genes which respond differently to the order of chemotherapeutic drug administered to rats and to identify microRNAs differentially expressed between tissues. 3) We used statistical modeling of gene expression data from humans exposed to acetaminophen in order to identify early indicators of hepatotoxicity. -------------------------------------------------------------------------------------------------- Completed the statistical analysis of microarray gene expression data from human subjects' blood who were dosed daily with 4 grams of acetaminophen. Genes predictive of an early acetaminophen response were identified. -------------------------------------------------------------------------------------------------- Continued the development of analysis strategies to derive of a mouse micro RNA (miRNA) atlas and to integrate miRNA data with mRNA gene expression data. -------------------------------------------------------------------------------------------------- Continued the development of a method to extend the Extracting Patterns and Identifying co-expressed Genes (EPIG) tool in support of count data from RNA-seq. -------------------------------------------------------------------------------------------------- Continued the development of analytical methodologies to extract biological themes from clustering of gene expression data and enrichment of biological processes or mechanistic pathways. -------------------------------------------------------------------------------------------------- Embarked on the development of bioinformatics strategies to utilize the NTP sentinel 1500 Genes set (i.e., the S1500) from RASL-Seq for capturing the totality of biological processes in rats tissue samples and human cell lines and compare the sentinel set to gene sets derived from microarray platforms and RNA-sequencing. -------------------------------------------------------------------------------------------------- Initiated the development of computational strategies to ascertain cross talk of adverse outcome pathways in gene expression data (RASL-Seq, microarray and RNA-Seq) derived from liver tissue samples of rats exposed to chemicals that share modes of action.

Project Start
Project End
Budget Start
Budget End
Support Year
9
Fiscal Year
2015
Total Cost
Indirect Cost
Name
U.S. National Inst of Environ Hlth Scis
Department
Type
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Lozoya, Oswaldo A; Martinez-Reyes, Inmaculada; Wang, Tianyuan et al. (2018) Mitochondrial nicotinamide adenine dinucleotide reduced (NADH) oxidation links the tricarboxylic acid (TCA) cycle with methionine metabolism and nuclear DNA methylation. PLoS Biol 16:e2005707
Duncan, Christopher G; Kondilis-Mangum, Hrisavgi D; Grimm, Sara A et al. (2018) Base-Resolution Analysis of DNA Methylation Patterns Downstream of Dnmt3a in Mouse Naïve B Cells. G3 (Bethesda) 8:805-813
Duncan, Christopher G; Grimm, Sara A; Morgan, Daniel L et al. (2018) Dosage compensation and DNA methylation landscape of the X chromosome in mouse liver. Sci Rep 8:10138
Nguyen, Thuy-Ai T; Grimm, Sara A; Bushel, Pierre R et al. (2018) Revealing a human p53 universe. Nucleic Acids Res :
Mav, Deepak; Shah, Ruchir R; Howard, Brian E et al. (2018) A hybrid gene selection approach to create the S1500+ targeted gene sets for use in high-throughput transcriptomics. PLoS One 13:e0191105
Muñoz, M D; Della Vedova, M C; Bushel, P R et al. (2018) The nitrone spin trap 5,5-dimethyl-1-pyrroline N-oxide dampens lipopolysaccharide-induced transcriptomic changes in macrophages. Inflamm Res 67:515-530
Osgood, Ross S; Upham, Brad L; Bushel, Pierre R et al. (2017) Secondhand Smoke-Prevalent Polycyclic Aromatic Hydrocarbon Binary Mixture-Induced Specific Mitogenic and Pro-inflammatory Cell Signaling Events in Lung Epithelial Cells. Toxicol Sci 157:156-171
Funderburk, Karen M; Auerbach, Scott S; Bushel, Pierre R (2017) Crosstalk between Receptor and Non-receptor Mediated Chemical Modes of Action in Rat Livers Converges through a Dysregulated Gene Expression Network at Tumor Suppressor Tp53. Front Genet 8:157
Bennett, Brian D; Bushel, Pierre R (2017) goSTAG: gene ontology subtrees to tag and annotate genes within a set. Source Code Biol Med 12:6
Bushel, P R; Fannin, R D; Gerrish, K et al. (2017) Blood gene expression profiling of an early acetaminophen response. Pharmacogenomics J 17:230-236

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