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Keith Shockley, Ph.D.

Biostatistics & Computational Biology Branch

Keith R. Shockley, Ph.D.
Keith R. Shockley, Ph.D.
Staff Scientist
Tel (919) 541-3033
P.O. Box 12233
Mail Drop A3-03
Research Triangle Park, NC 27709

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Research Summary

Keith Shockley, Ph.D., conducts research at the interface of environmental science and data science. He also serves as a bioinformatician for the National Toxicology Program (NTP) and an adjunct member of the Biomolecular Screening Branch. His central goal is to develop and apply computational approaches to analyze high dimensional data sets generated from quantitative high throughput screening (qHTS), functional genomics and other complex biological systems used to study environmental health.

Shockley’s methodological research focuses on the construction of novel ways to detect actives and minimize false negatives in toxicity testing and environmental genomics. A major aim of this work is to build computational frameworks to determine the toxicological relevance of a chemical in qHTS experiments that take into account different variance structures that often accompany such data. In addition, he pursues suitable statistical methods to resolve differences arising from multifactorial study designs used in toxicogenomics investigations.

Shockley also collaborates with NIEHS researchers in efforts to advance toxicity testing and better understand biological response to environmental stress. He analyzes and interprets data generated within the Tox21 program and contributes to the design and analysis of environmental health studies conducted within the institute. This work entails the identification of putative toxicants from in vitro screening experiments and the assessment of gene expression responses associated with spontaneous and chemical-induced carcinogenesis. In addition, he implements suitable bioinformatics approaches for functional genomics evaluations and helps to develop new data analysis pipelines for DNTP studies.

Selected Publications by Research Area

Computational Methods

  1. Shockley KR. Estimating potency in high-throughput screening experiments by maximizing the rate of change in weighted Shannon entropy. Scientific Reports 2016 6:27897.
  2. Shockley KR. Quantitative high-throughput screening data analysis: challenges and recent advances. Drug Discovery Today 2015 20(3):296-300. [Abstract]
  3. Shockley KR. Using weighted entropy to rank chemicals in quantitative high-throughput screening experiments. Journal of Biomolecular Screening 2014 19(3):344-353. [Abstract]
  4. Ray M, Shockley K, Kissling G. Minimizing systematic errors in quantitative high throughput screening data using standardization, background subtraction, and non-parametric regression. Journal of Experimental Secondary Science 2014 3(2).
  5. Shockley KR. A three-stage algorithm to make toxicologically relevant activity calls from quantitative high throughput screening data. Environmental Health Perspectives 2012 120(8):1107-15. [Abstract]
  6. Li, R., WernTsaih, S., Shockley, K., Stylianou, I. M., Wergedal, J., Paigen, B. & Churchill, G. A. (2006). Structural model analysis of multiple quantitative traits. PLoS Genetics. 2: e114. [Abstract]  

In Vitro Screening

  1. Boyd WA, Smith MV, Co CA, Pirone JR, Rice JR, Shockley KR, Freedman JH. Developmental effects of the ToxCast™ Phase I and II chemicals in Caenorhabditis elegans and corresponding responses in zebrafish, rats, and rabbits. Environmental Health Perspectives 2016 124(5):586-593. [Abstract]
  2. Pei Y, Peng J, Behl M, Sipes NS, Shockley KR, Rao MS, Tice RR, Zeng X. Comparative neurotoxicity screening in human iPSC-derived neural stem cells, neurons and astrocytes. Brain Research 2016 1638(Pt A):57-73. [Abstract]
  3. Chen S, Hsieh JH, Huang R, Sakamuru S , Hsin LY, Xia M, Shockley KR, Auerbach S, Kanaya N, Lu H, Svoboda D, Witt KL, Merrick BA, Teng CT, Tice RR. Cell-based high-throughput screening for aromatase inhibitors in the Tox21 10K library. Toxicological Sciences 2015 147(2):446-457. [Abstract]
  4. Huang R, Sakamuru S, Martin MT, Reif DM, Judson RS, Houck KA, Casey W, Hsieh JH, Shockley KR, Ceger P, Fostel J, Witt KL, Tong W, Rotroff DM, Zhao T, Shinn P, Simeonov A, Dix DJ, Austin CP, Kavlock RJ, Tice RR, Xia M. Profiling of the Tox21 10K compound library for agonists and antagonists of the estrogen receptor alpha signaling pathway. Scientific Reports 2014 4():5664-. [Abstract]
  5. Teng CT, Goodwin B, Shockley K, Xia M, Huang R, Norris J, Merrick BA, Jetten AM, Austin CP, Tice RR. Bisphenol A affects androgen receptor function via multiple mechanisms. Chemico-biological interactions 2013; 203(3): 556-564. [Abstract]


  1. Dunnick JK, Merrick BA, Brix A, Morgan DL, Gerrish K, Flake G, Foley J and Shockley K. Molecular changes in the nasal cavity after N,N-Dimethyl-p-toluidine exposure. Toxicologic Pathology 2016 (In Press, 2016).
  2. Hayes SA, Pandiri AR, Ton TV, Hong HH, Clayton NP, Shockley KR, Peddada SD, Gerrish K, Wyde M, Sills RC, Hoenerhoff MJ. Renal cell carcinomas in vinylidene chloride-exposed male B6C3F1 mice are characterized by oxidative stress and TP53 pathway dysregulation. Toxicologic Pathology 2016 44(1): 71-87. [Abstract]
  3. Bhusari S, Pandiri AR, Nagai H, Wang Y, Foley J, Hong HH, Ton TV, DeVito M, Shockley KR, Peddada SD, Gerrish KE, Malarkey DE, Hooth MJ, Sills RC, Hoenerhoff MJ. Genomic profiling reveals unique molecular alterations in hepatoblastomas and adjacent hepatocellular carcinomas in B6C3F1 Mice. Toxicological Pathology 2015 43(8): 1114-1126.
  4. Blackshear PE, Pandiri AR, Nagai H, Bhusari S, Hong L, Ton TV, Clayton NP, Wyde M, Shockley KR, Peddada SD, Gerrish KE, Sills RC, Hoenerhoff MJ. Gene expression of mesothelioma in vinylidene chloride-exposed F344/N rats reveal immune dysfunction, tissue damage, and inflammation pathways. 2015 Toxicologic Patholology 43(2): 171-185. [Abstract]
  5. Blackshear PE, Pandiri AR, Ton TV, Clayton NP, Shockley KR, Peddada SD, Gerrish KE, Sills RC, Hoenerhoff MJ. Spontaneous mesotheliomas in F344/N rats are characterized by dysregulation of cellular growth and immune function pathways. Toxicological Pathology 42(5):863-876. [Abstract]
  6. Hoenerhoff, M.J., Pandiri, A.R., Snyder, S.A., Hong, H.H.L., Ton, T.V., Peddada, S., Shockley, K., Witt, K., Chan, P., Rider, C.V., Kooistra, L., Nyska, A., Sills, R.C. (2013). Hepatocellular carcinomas in B6C3F1 mice treated with Ginkgo biloba extract for two years differ from spontaneous liver tumors in cancer gene mutations and genomic pathways. Toxicologic Pathology 41(6):826-841. [Abstract]
  7. Pandiri AR, Sill RC, Ziglioli V, Ton TV, Hong HH, Lahousse SA, Gerrish KE, Auerbach SS, Shockley KR, Bushel PR, Peddada SD, Hoenerhoff MJ. (2012). Differential Transcriptomic Analysis of Spontaneous Lung Tumors in B6C3F1 Mice: Comparison to Human Non-Small Cell Lung Cancer. Toxicologic Pathology 40(8): 1141-1159.
  8. Dunnick JK , Brix A, Cunny H, Vallant M , Shockley KR. Characterization of polybrominated diphenyl ether toxicity in Wistar Han rats and use of liver microarray data for predicting disease susceptibilities. Toxicologic Pathology 2012 40(1):93-106. [Abstract]
  9. Hoenerhoff, M.J., Pandiri, A.P., Lahousse, S.A., Hong, H.H., Ton, T.V., Masinde, T., Auerbach, S., Gerrish, K., Bushel, P.R., Shockley, K.R., Peddada, S.D. Sills, R.C. (2011). Global gene profiling of spontaneous hepatocellular carcinoma in B6C3F1 mice: similarities in the molecular landscape with human liver cancer. Toxicologic pathology, 39:678-699. [Abstract]

Genetics and Complex Traits Analysis

  1. French JE, Gatti DM, Morgan DL, Kissling GE, Shockley KR, Knudsen GA, Shepard KG, Price HC, King D, Witt KL, Pedersen LC, Munger SC, Svenson KL, Churchill GA. Diversity outbred mice identify population-based exposure thresholds and genetic factors that influence benzene-induced genotoxicity. Environmental Health Perspectives 2015 123(3): 237-245.
  2. Shockley KR, Witmer D, Burgess-Herbert SL, Paigen B, Churchill GA. Effects of atherogenic diet on hepatic gene expression across mouse strains. Physiological Genomics 2009 39(3):172-182.
  3. Ackert-Bicknell, C. L., Shockley, K. R., Horton, L. G., Lecka-Czernik, B., Churchill, G. A. & Rosen, C. J. Strain specific effects of Rosiglitazone on bone mass, body composition and serum IGF-1. Endocrinology 2009; 150:1330-1340. [Abstract]
  4. Stylianou IM, Affourtit JP, Shockley KR, Abdi FA, Sanjeev B, Rollins J, Churchill GA, Paigen BA. Applying Gene Expression, Proteomics and SNP Analysis for complex trait gene identification. Genetics 2008 178(3):1795-1805. [Abstract]
  5. Cui X, Affoutit J, Shockley KR, Woo Y, Churchill GA. Inheritance patterns of transcript levels in F1 hybrid mice. Genetics 2006 174(2):627-637. [Abstract]  
  6. Shockley, K. R., Churchill, G.A. Gene expression analysis of mouse chromosome substitution strains. Mammalian Genome. 2006 17: 598-614. [Abstract]

Other Genomics Studies

  1. George-Raizen JB, Shockley KR, Trojanowski NF, Lamb AL, Raizen DM. Dynamically-expressed prion-like proteins form a cuticle in the pharynx of Caenorhabditis elegans. Biology Open 2014 3(11):1139-1149. [Abstract]
  2. Arnardottir ES, Nikonova EV, Shockley KR, Podtelezhnikov AA, Anafi RC, Tanis KQ, Maislin G, Stone DJ, Renger JJ, Winrow CJ, Pack AI. Blood-gene expression reveals reduced circadian rhythmicity in individuals resistant to sleep deprivation. Sleep 2014 37(10):1589-1600.
  3. Anafi RC, Pellegrino R, Shockley KR, Romer M, Tufik S, Pack AI. (2013). Sleep is not just for the brain: Transcriptional responses to sleep in peripheral tissues. BMC Genomics 2013 14: 362.
  4. Shockley, K. R., Lazarenko, O. P., Czernik, P. J., Rosen, C. J., Churchill, G. A. & Lecka-Czernik, B. (2009). PPARgamma2 nuclear receptor controls multiple regulatory pathways of osteoblast differentiation from marrow mesenchymal stem cells. Journal of Cellular Biochemistry. 106: 232-246. [Abstract]  
  5. Shockley, K. R., Rosen, C. J., Churchill, G. A. & Lecka-Czernik, B. (2007). PPARgamma2 regulates a molecular signature of marrow mesenchymal stem cells. PPAR Research 2007:81219. [Abstract]  
  6. Shockley, K. R., Churchill, G.A. Gene expression analysis of mouse chromosome substitution strains. Mammalian Genome. 2006 17: 598-614. [Abstract]  
  7. Shockley KR, Scott KL, Pysz MA, Conners SB, Johnson MR, Montero CI, Wolfinger RD, Kelly RM. Genome-wide transcriptional variation within and between steady states for continuous growth of the hyperthermophile Thermotoga Maritima. Applied and Environmental Microbiology 2005 71(9):5572-5576.
  8. Shockley KR, Ward DE, Chhabra SR, Conners SB, Montero CI, Kelly RM. Heat shock response by the hyperthermophilic archaeon Pyrococcus furiosus. Applied and Environmental Microbiology 2003 69(4):2365-2371.

Supplementary Material

    1. WES example code(2KB)

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