Initiated an implementation of a strategy to detect the exonization of transposable elements (TEs) in human coding sequences. TEs have long been regarded as selfish or junk DNA having little or no role in the regulation or functioning of the human genome. However, over the past several years this view came to be challenged as several studies provided anecdotal as well as global evidence for the contribution of transposable elements to the regulatory and coding needs of human genes. We explored the incorporation and regulation of coding sequences donated by TEs using RNA-seq, ChIP-seq, CAGE, and DNase1 hyspersensitivity data in two human hematopoietic cell-lines characterized by the ENCODE project. We compared transcriptome assembly with and without the aid of a reference transcriptome and found that the percentage of genes that incorporate transposable elements in their coding sequences is significantly greater than that obtained from the reference transcriptome assemblies using two gene models. Using a data integration approach, we demonstrated the epigenetic regulation of the TE derived coding sequences. -------------------------------------------------------------------------------------------------- Continued the development of procedures for the analysis of gene expression and next generation sequence data. We developed a novel way to analyze RNA-Seq data for detection of alternative polyadenylation (APA). Using a Poisson hidden Markov model (PHMM) to detect high and low expression states of RNA-Seq expression at the 3'untranslated region (UTR), we identified genes that have tissue specific APA between cortex (brain) and liver tissues in the human. We also show that analyzing the 3'UTR with RNA-Seq in this manner is advantageous than using microarray profiling given the variability of the probes at the 3'end of the genes. -------------------------------------------------------------------------------------------------- Continued the collaborative support of investigators'research. 1) We devised of an analytical method to associate differential gene expression with the presumed formation of RNA loops in regions of high GC content. 2) We employed bioinformatics strategies to predict toxicity in the rat liver from exposure to toxicants using gene expression data. We also derived of a bioinformatics strategy to differentiate modes of actions for these toxicants based on regulatory pathways enriched by differentially expressed genes (data from microarray and RNA-Seq platforms). 3) 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. 4) We developed an analysis workflow called PIPERS (Pipeline Informatics for Processing and Examining RNA-Seq) to detect allele-specific expression in two NTP mouse strains. 5) We used statistical modeling of gene expression data from humans exposed to acetaminophen in order to identify early indicators of hepatotoxicity.

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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
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
Manrai, Arjun K; Cui, Yuxia; Bushel, Pierre R et al. (2017) Informatics and Data Analytics to Support Exposome-Based Discovery for Public Health. Annu Rev Public Health 38:279-294
Kim, Sang Hwa; Trinh, Anthony T; Larsen, Michele Campaigne et al. (2016) Tunable regulation of CREB DNA binding activity couples genotoxic stress response and metabolism. Nucleic Acids Res :
Smith, Aaron; Calley, John; Mathur, Sachin et al. (2016) The Rat microRNA body atlas; Evaluation of the microRNA content of rat organs through deep sequencing and characterization of pancreas enriched miRNAs as biomarkers of pancreatic toxicity in the rat and dog. BMC Genomics 17:694
Fannin, R D; Gerrish, K; Sieber, S O et al. (2016) Blood transcript immune signatures distinguish a subset of people with elevated serum ALT from others given acetaminophen. Clin Pharmacol Ther 99:432-41
Ciencewicki, Jonathan M; Verhein, Kirsten C; Gerrish, Kevin et al. (2016) Effects of mannose-binding lectin on pulmonary gene expression and innate immune inflammatory response to ozone. Am J Physiol Lung Cell Mol Physiol 311:L280-91
Li, Jianying; Bushel, Pierre R (2016) EPIG-Seq: extracting patterns and identifying co-expressed genes from RNA-Seq data. BMC Genomics 17:255
Bourdon-Lacombe, Julie A; Moffat, Ivy D; Deveau, Michelle et al. (2015) Technical guide for applications of gene expression profiling in human health risk assessment of environmental chemicals. Regul Toxicol Pharmacol 72:292-309
Verhein, Kirsten C; McCaw, Zachary; Gladwell, Wesley et al. (2015) Novel Roles for Notch3 and Notch4 Receptors in Gene Expression and Susceptibility to Ozone-Induced Lung Inflammation in Mice. Environ Health Perspect 123:799-805

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