Completed 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 hypersensitivity 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. -------------------------------------------------------------------------------------------------- Completed 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 showed 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 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). 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 developed an analysis workflow called PIPERS (Pipeline Informatics for Processing and Examining RNA-Seq) to detect allele-specific expression in two NIEHS/National Toxicology Program mouse strains. In addition, we developed analytical strategies to detect differentially methylated region from bisulfite sequencing data. 4) We used statistical modeling of gene expression data from humans exposed to acetaminophen in order to identify early indicators of hepatotoxicity. 5) We developed an improved support vector machines (SVMs) classifier to suit multiclass predictions based on gene expression data. 6) We integrated transcription factor binding information with genotype data and microarray gene expression data to identify population differences between transcript-regulator expression quantitative trait loci (TReQTLs).

Project Start
Project End
Budget Start
Budget End
Support Year
7
Fiscal Year
2013
Total Cost
$664,080
Indirect Cost
City
State
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Zip Code
Lowe, Julie M; Menendez, Daniel; Bushel, Pierre R et al. (2014) p53 and NF-?B coregulate proinflammatory gene responses in human macrophages. Cancer Res 74:2182-92
SEQC/MAQC-III Consortium (2014) A comprehensive assessment of RNA-seq accuracy, reproducibility and information content by the Sequencing Quality Control Consortium. Nat Biotechnol 32:903-14
Lu, Jun; Bushel, Pierre R (2013) Dynamic expression of 3' UTRs revealed by Poisson hidden Markov modeling of RNA-Seq: implications in gene expression profiling. Gene 527:616-23
Davis, Barbara J; Risinger, John I; Chandramouli, Gadisetti V R et al. (2013) Gene expression in uterine leiomyoma from tumors likely to be growing (from black women over 35) and tumors likely to be non-growing (from white women over 35). PLoS One 8:e63909
Huang, Lingkang; Zhang, Hao Helen; Zeng, Zhao-Bang et al. (2013) Improved Sparse Multi-Class SVM and Its Application for Gene Selection in Cancer Classification. Cancer Inform 12:143-53
Zhang, Liwen; Simpson, Dennis A; Innes, Cynthia L et al. (2013) Gene expression signatures but not cell cycle checkpoint functions distinguish AT carriers from normal individuals. Physiol Genomics 45:907-16
Bushel, Pierre R; Nielsen, Dahlia; Tong, Weida (2009) Proceedings of the First International Conference on Toxicogenomics Integrated with Environmental Sciences (TIES-2007). BMC Proc 3 Suppl 2:S1
Chou, Jeff W; Bushel, Pierre R (2009) Discernment of possible mechanisms of hepatotoxicity via biological processes over-represented by co-expressed genes. BMC Genomics 10:272
Bushel, Pierre R (2009) Clustering of gene expression data and end-point measurements by simulated annealing. J Bioinform Comput Biol 7:193-215