Pierre Bushel, Ph.D., and his staff use their expertise in bioinformatics to design analytical methodologies for genomic data analysis and develop databases for environmental informatics. Their research focuses on integrating phenotypic observations, end-point measurements and associated biological information with expression and genomics data for a better understanding of the biological mechanisms and pathways that are perturbed by stressors. The group has several ongoing projects:
Specialized neural networks for classification and prediction
Microarray intelligent knowledge EXtraction (AREX) for gene expression data mining
Biological theme extraction from expression data and biomedical literature
Environmental- and Toxico-genomics
Modeling multidimensional toxicity states
Genome characteristics profiling
Association of genome characteristics and perturbed expression patterns
In addition, Bushel and his group provide bioinformatics, data analysis, computational biology and statistical genetics/genomics support as well as software, database and application development expertise to NIEHS Division of Intramural Research investigators at no cost.
Selected Publications
Boedigheimer MJ , Wolfinger RD, Bass MB, Bushel PR , Chou JW , Cooper M , Corton JC, Fostel J, Hester S, Lee JS, Liu F , Liu J, Qian H , Quackenbush J, Pettit S, Thompson KL. Sources of variation in baseline gene expression levels from
toxicogenomics study control animals across multiple laboratories. BMC genomics 2008 9:285. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18549499)
Huang L, Heinloth AN, Zhao-Bang Z, Paules RS, Bushel PR.
Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants. BMC Genomics. 2008 Jun 16;9:288.[Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18558008)
Lobenhofer EK, Auman JT, Blackshear PE, Boorman GA, Bushel PR, Cunningham ML, Fostel JM, Gerrish K, Heinloth AN, Irwin RD, Malarkey DE, Merrick BA, Sieber SO, Tucker CJ, Ward SM, Wilson RE, Hurban P, Tennant RW, Paules RS. Gene expression response in target organ and whole blood varies as a function of target organ injury phenotype.
Genome Biol. 2008 Jun 20;9(6):R100. [Epub ahead of print]
Huang L, Heinloth AN, Zeng ZB, Paules RS, Bushel PR.
Genes related to apoptosis predict necrosis of the liver as a phenotype observed in rats exposed to a compendium of hepatotoxicants. BMC Genomics. 2008 Jun 16;9(1):288. [Epub ahead of print]
Boedigheimer MJ, Wolfinger RD, Bass MB, Bushel PR, Chou JW, Cooper M, Corton JC, Fostel J, Hester S, Lee JS, Liu F, Liu J, Qian HR, Quackenbush J, Pettit S, Thompson KL.
Sources of variation in baseline gene expression levels from toxicogenomics study control animals across multiple laboratories. BMC Genomics. 2008 Jun 12;9(1):285. [Epub ahead of print]
Jin YH, Dunlap PE , McBride SJ, Al-Refai H, Bushel PR, Freedman JH. Global transcriptome and deletome profiles of yeast exposed to transition metals. PLoS Genetics 2008 4(4):e1000005-. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=18437200)
Waters M, Stasiewicz S, Merrick BA, Tomer K, Bushel P, Paules R, Stegman N, Nehls G , Yost KJ, Johnson CH, Gustafson SF, Xirasagar S, Xiao N, Huang C-C, Boyer P, Chan DD, Pan Q, Gong H, Taylor J, Fostel J, Choi D, Rashid A, Ahmed A, Howle R, Selkirk J, Tennant R . CEBS: Chemical Effects in Biological Systems. A public data repository integrating study design and toxicity data with microarray and proteomics data.. Nucleic acids research 2008 36():D892-D900. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17962311)
Bushel PR, Heinloth AN, Li J, Huang L, Chou JW, Boorman GA, Malarkey DE, Houle CD, Ward SM, Wilson RE, Fannin RD, Russo MW, Watkins PB, Tennant RW, Paules RS. Blood gene expression signatures predict exposure levels. Proc Natl Acad Sci U S A. 2007 Nov 13;104(46):18211-6. Epub 2007 Nov 2. [Abstract](http://www.ncbi.nlm.nih.gov/pubmed/17984051?ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Chou JW, Zhou T, Kaufmann WK, Paules RS, Bushel PR. Extracting gene expression patterns and identifying co-expressed genes from microarray data. BMC bioinformatics 2007 8(1):427-427. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17980031)
Zhou T, Chou J, Mullen TE, Elkon R, Zhou Y, Simpson DA, Bushel PR, Paules RS, Lobenhofer EK, Hurban P, Kaufmann WK. Identification of primary transcriptional regulation of cell-cycle-regulated genes upon DNA damage. Cell cycle (Georgetown, Tex.) 2007 8: 972-981. [Abstract] (http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=17404513)
Zhou T, Chou J, Zhou Y, Simpson DA, Cao F, Bushel PR, Paules RS, Kaufmann WK. Ataxia telangiectasia-mutated dependent DNA damage checkpoint functions regulate gene expression in human fibroblasts. Mol Cancer Res. 2007 Aug; 5(8): 813-22. [Abstract](http://www.ncbi.nlm.nih.gov/sites/entrez?Db=pubmed&Cmd=ShowDetailView&TermToSearch=17699107&ordinalpos=1&itool=EntrezSystem2.PEntrez.Pubmed.Pubmed_ResultsPanel.Pubmed_RVDocSum)
Fostel JM, Burgoon L, Zwickl C, Lord P, Corton JC, Bushel PR, Cunningham M, Fan L, Edwards SW, Hester S, Stevens J, Tong W, Waters M, Yang C, Tennant R. Toward a checklist for exchange and interpretation of data from a toxicology study. Toxicol Sci. 2007 Sep;99(1):26-34. Epub 2007 Apr 17.
Bushel PR, Wolfinger RD, Gibson G. Simultaneous clustering of gene expression data with clinical chemistry and pathological evaluations reveals phenotypic prototypes. BMC Syst Biol. 2007 Feb 23;1:15. [Abstract](http://www.ncbi.nlm.nih.gov/sites/entrez?db=pubmed&cmd=search&term=Simultaneous%20clustering%20of%20gene%20expression%20data%20with%20clinical%20chemistry%20and%20pathological%20evaluations%20reveals%20phenotypic%20prototypes)
Zhou T, Chou J, Mullen TE, Elkon R, Zhou Y, Simpson DA, Bushel PR, Paules RS, Lobenhofer EK, Hurban P, Kaufmann WK. Identification of primary transcriptional regulation of cell cycle-regulated genes upon DNA damage. Cell Cycle. 2007 Apr 15;6(8):972-81. Epub 2007 Apr 19.
Xirasagar S, Gustafson SF, Huang CC, Pan Q, Fostel J, Boyer P, Merrick BA, Tomer KB, Chan DD, Yost KJ 3rd, Choi D, Xiao N, Stasiewicz S, Bushel P, Waters MD. Chemical effects in biological systems (CEBS) object model for toxicology data, SysTox-OM: design and application. Bioinformatics. 2006 Apr 1;22(7):874-82. Epub 2006 Jan 12. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16410321)
Innes CL, Heinloth AN, Flores KG, Sieber SO, Deming PB, Bushel PR, Kaufmann WK, Paules RS. ATM requirement in gene expression responses to ionizing radiation in human lymphoblasts and fibroblasts. Mol Cancer Res. 2006 Mar;4(3):197-207. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16547157)
Zhou T, Chou JW, Simpson DA, Zhou Y, Mullen TE, Medeiros M, Bushel PR, Paules RS, Yang X, Hurban P, Lobenhofer EK, Kaufmann WK. Profiles of global gene expression in ionizing-radiation-damaged human diploid fibroblasts reveal synchronization behind the G1 checkpoint in a G0-like state of quiescence. EHP. 2006 Apr;114(4):553-9. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16581545)
Fostel J, Choi D, Zwickl C, Morrison N, Rashid A, Hasan A, Bao W, Richard A, Tong W, Bushel PR, Brown R, Bruno M, Cunningham ML, Dix D, Eastin W, Frade C, Garcia A, Heinloth A, Irwin R, Madenspacher J, Merrick BA, Papoian T, Paules R, Rocca-Serra P, Sansone AS, Stevens J, Tomer K, Yang C, Waters M. Chemical effects in biological systems--data dictionary (CEBS-DD): a compendium of terms for the capture and integration of biological study design description, conventional phenotypes, and 'omics data. Toxicol Sci. 2005 Dec;88(2):585-601. Epub 2005 Sep 8. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16150882)
Bammler T, Beyer RP, Bhattacharya S, Boorman GA, Boyles A, Bradford BU, Bumgarner RE, Bushel PR, Chaturvedi K, Choi D, Cunningham ML, Deng S, Dressman HK, Fannin RD, Farin FM, Freedman JH, Fry RC, Harper A, Humble MC, Hurban P, Kavanagh TJ, Kaufmann WK, Kerr KF, Jing L, Lapidus JA, Lasarev MR, Li J, Li YJ,Lobenhofer EK, Lu X, Malek RL, Milton S, Nagalla SR, O'malley JP, Palmer VS, Pattee P, Paules RS, Perou CM, Phillips K, Qin LX, Qiu Y, Quigley SD, Rodland M, Rusyn I, Samson LD, Schwartz DA, Shi Y, Shin JL, Sieber SO, Slifer S, Speer MC, Spencer PS, Sproles DI, Swenberg JA, Suk WA, Sullivan RC, Tian R, Tennant RW, Todd SA, Tucker CJ, Van Houten B, Weis BK, Xuan S, Zarbl H; Members of the Toxicogenomics Research Consortium. Standardizing global gene expression analysis between laboratories and across platforms. Nat Methods. 2005 May;2(5):351-6. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15846362)
Chou JW, Paules RS., Bushel PR. Systematic Variation Normalization in Microarray Data to Get Gene Expression Comparison Unbiased. JBCB 3, 225-41, 2005. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15852502)
Leung E, Bushel PR. PAGE: phase-shifted analysis of gene expression. Bioinformatics. 2006 Feb 1;22(3):367-8. Epub 2005 Dec 1. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=16322047)
Bushel PR. Toxicogenomics: Principles and Applications, Chapter5 - Databases for Toxicogenomics. Editors: Hisham K. Hamadeh and Cynthia A. Afshari, John Wiley and Sons, Inc. 2004.
Mattes WB, Pettit SD, Sansone S, Bushel PR, Waters MD. Database Development in Toxicogenomics: Issues and Efforts. EHP 112(4) 495-505, 2004. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15033600)
Qin LX, Kerr KF, Contributing Members of the Toxicogenomics Research Consortium.
Empirical evaluation of data transformations and ranking statistics for microarray analysis. Nucleic Acids Res. 32(18):5471-5479, 2004. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=15479783)
Xue R., Li, J, Streveler DJ. Microarray Gene Expression Profile Data Mining Model for Clinical Cancer Research Proceeding of the 37th Hawaii International Conference on System Sciences, 2004.
Bushel PR, Hamadeh HK, Bennett L, Green J, Albeson A, Misener S, Afshari CA, Paules RS. Computational Selection of Distinct Class- and Subclass- Specific Gene Expression Signatures. Journal of Biomedical Informatics 35: 160-170, 2003. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12669979)
Heinloth AN, Shackelford RE, Innes CL, Bennett L, Li L, Amin RP, Sieber SO, Flores KG, Bushel PR, Paules RS. Abstract Identification of distinct and common gene expression changes after oxidative stress and gamma and ultraviolet radiation. Molecular Carcinogenesis, 37(2): 65-82, 2003. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12766906)
Heinloth AN, Shackelford RE, Innes CL, Bennett L, Li L, Amin RP, Sieber SO, Flores KG, Bushel PR, Paules RS. ATM-dependent and -independent gene expression changes in response to oxidative stress, gamma irradiation, and UV irradiation. Radiation Research 160, 273-290, 2003. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12926986)
Kerr MK, Afshari C, Bennett L, Bushel P, Martinez J, Walker N, Churchill GA. Statistical Analysis of a Gene Expression Microarray Experiment. Statistica Sinica 12(1): 203-217, 2002.
Hamadeh HK, Bushel PR, Jayadev J, Martin K, DiSorbo O, Sieber S, Bennett L, Tennant R, Stoll R, Barrett JC, Blanchard K, Paules RS, Afshari CA. Prediction of Compound Signature Using High Density Gene Expression Profiling. Toxicological Sciences, 67: 232-240, 2002. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=12011482)
Bushel PR, Hamadeh H, Bennett L, Sieber S, Martin K, Nuwaysir EF, Hayes K, Reynolds K, Paules R, Afshari CA.MAPS: A MicroArray Project System for Gene Expression Experiment Information and Data Validation. Bioinformatics 17(6): 564-565, 2001. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11395436)
Wolfinger RD, Gibson G, Wolfinger ED, Bennett L, Hamadeh H, Bushel P, Afshari C, Paules RS. Assessing gene significance from cDNA microarray expression data via mixed models. Journal of Computational Biology 8(6): 625-637, 2001. [Abstract](http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=pubmed&dopt=Abstract&list_uids=11747616)
P.O. Box 12233
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