Integrative and Systems Genetics
Behavioral Bioinformatics
Genome-Phenome Integration

Dr. Chesler's research emphasizes the integration of genomic and phenomic resources. Her current research emphasizes ontological discovery from the extraction of sets of genes and phenotypes from large empirical data sets. These efforts include the production and characterization of the Collaborative Cross and studies involving the BXD Recombinant Inbred Lines. Dr. Chesler and colleagues integrate statistical and combinatoric approaches to systems genetic analysis. Her previous research explored two important issues pertaining to the widespread use of standard inbred mouse strains for this purpose. She has previously established several algorithmic, statistical and population based hurdles to the use of common inbred strains as a genetic mapping panel (Chesler et al 2001, Mhyre et al, 2005). She has also examined issues in combining data from genetic projects across labs, extracting specific factors responsible for genetic interactions with the laboratory environment using a computational analysis of a large data archive featuring observations of a single behavioral measurement acquired thousands of times in the laboratory of one investigator (Chesler et al, 2002a,b).

Her post-doctoral research in the laboratory of Dr. Robert Williams was with the large collaborative Gene Network project (Chesler et al, 2004), which successfully incorporates data from basepair to behavior. Using the BXD recombinant inbred strains as a mapping panel, this group has used oligonucleotide microarrays as a phenotype to determine the genetic regulation of gene expression. Because the mapping panel has been available for over 20 years, Dr. Chesler has been able to incorporate hundreds of legacy phenotypes into this free, public internet resource (Chesler et al, 2003). In addition to the assembly of this database, Dr. Chesler has designed many of the analytic features on the site including tools for multivariate analysis, trait clustering of gene expression and systems level phenotypes in QTL maps and graph visualization. She is currently involved in scaling these tools for high-dimensional data in a collaborative effort with computer scientists at University of Tennessee, Knoxville.

• Chesler EJ. Book review. Genes Brain Behav. 2006 Mar;5(2):207. No abstract available. PMID: 16507012
• Kempermann G, Chesler EJ, Lu L, Williams RW, Gage FH. Natural variation and genetic covariance in adult hippocampal neurogenesis. Proc Natl Acad Sci U S A. 2006 Jan 17;103(3):780-5. Epub 2006 Jan 9. PMID: 16407118
• Li H, Chen H, Bao L, Manly KF, Chesler EJ, Lu L, Wang J, Zhou M, Williams RW, Cui Y. Integrative genetic analysis of transcription modules: towards filling the gap between genetic loci and inherited traits. Hum Mol Genet. 2006 Feb 1;15(3):481-92. Epub 2005 Dec 21. PMID: 16371421
• Vazquez-Chona FR, Khan AN, Chan CK, Moore AN, Dash PK, Hernandez MR, Lu L, Chesler EJ, Manly KF, Williams RW, Geisert EE Jr. Genetic networks controlling retinal injury. Mol Vis. 2005 Nov 4;11:958-70. PMID: 16288200
• Bennett B, Carosone-Link PJ, Lu L, Chesler EJ, Johnson TE. Genetics of body weight in the LXS recombinant inbred mouse strains. Mamm Genome. 2005 Oct;16(10):764-74. Epub 2005 Oct 29. PMID: 16261418
• Matthews DB, Bhave SV, Belknap JK, Brittingham C, Chesler EJ, Hitzemann RJ, Hoffmann PL, Lu L, McWeeney S, Miles MF, Tabakoff B, Williams RW. Complex genetics of interactions of alcohol and CNS function and behavior. Alcohol Clin Exp Res. 2005 Sep;29(9):1706-19. PMID: 16205371

• Vazquez-Chona FR, Khan AN, Chan CK, Moore AN, Dash PK, Hernandez MR, Lu L, Chesler EJ, Manly KF, Williams RW, and Geisert EE Jr. (2005). Genetic networks controlling retinal injury. Mol Vis. 11: 958-70.
• Bennett B, Carosone-Link PJ, Lu L, Chesler EJ, Johnson TE. (2005). Genetics of body weight in the LXS recombinant inbred mouse strains. Mamm Genome. 16(10): 764-74.
• Matthews DB, Bhave SV, Belknap JK, Brittingham C, Chesler EJ, Hitzemann RJ, Hoffmann PL, Lu L, McWeeney S, Miles MF, Tabakoff B, and Williams RW. (2005). Complex genetics of interactions of alcohol and CNS function and behavior. Alcohol Clin Exp Res. 29(9): 1706-19.
• Mogil JS, Miermeister F, Seifert F, Strasburg K, Zimmermann K, Reinhold H, Austin JS, Bernardini N, Chesler EJ, Hofmann HA, Hordo C, Messlinger K, Nemmani KV, Rankin AL, Ritchie J, Siegling A, Smith SB, Sotocinal S, Vater A, Lehto SG, Klussmann S, Quirion R, Michaelis M, Devor M, and Reeh PW. (2005). Variable sensitivity to noxious heat is mediated by differential expression of the CGRP gene. Proc Natl Acad Sci. 102(36): 12938-43.
• Welton AR, Chesler EJ, Sturkie C, Jackson AU, Hirsch GN, and Spindler KR. (2005). Identification of quantitative trait loci for susceptibility to mouse adenovirus type 1. J Virol. 79(17): 11517-22.
• Baldwin NE, Chesler EJ, Kirov S, Langston MA, Snoddy JR, Williams RW, and Zhang B. (2005). Computational, integrative, and comparative methods for the elucidation of genetic coexpression networks. J Biomed Biotechnol. 2005(2): 172-80.
• Chesler, EJ, Lu L, Shou S, Qu Y, Gu J, Wang J, Hsu HC, Mountz JD, Baldwin N, Langston MA, Threadgill DW, Manly KF, a nd Williams RW. (2005). Complex trait analysis of gene expression uncovers polygenic and pleiotropic networks that modulate nervous system function. Nature Genetics. 37(3): 233-42.
• Mhyre T, Chesler EJ, Thiruchelvam M, Lungu C, Dory Slectra D, Fry J, and Richfield EK. (2005). Heritability, correlations, and in silico mapping of locomotor behavior and neurochemistry in inbred strains of mice. Genes, Brain, Behavior. 4(4): 209-28.
• Chesler, EJ, Lu L, Wang J, Williams RW, and Manly KF. (2004). WebQTL: rapid exploratory analysis of gene expression and genetic networks for brain and behavior. Nature Neuroscience. 7(5): 485-486.
• Chesler, EJ and Langston MA. (2005). Combinational genetic regulatory network analysis tools for high throughput transcriptomic data. First Annual RECOMB Satellite Workshop on Systems Biology and the Second Annual RECOMB Satellite Workshop on Regulatory Genomics