Project H: Causal Modeling of Genetic Systems

Gary A Churchill (Jackson)


Mathematical modeling is a defining feature of systems biology. Of the many available approaches to modeling, graphical models are unique in their promise to reveal causal relationships and thus to predict response to perturbations based on the correlation structure of multivariate data. Directed graphical models can be inferred from genetic data using genotype as a causal anchor. The questions posed in this project are whether these genotype-driven graphical models can make valid predictions of phenotype and to what extent do the inferred graphical structures reflect the underlying network of biochemical reactions.

Center related publications

Modeling host genetic regulation of influenza pathogenesis in the collaborative cross
Ferris MT, Aylor DL, Bottomly D, Whitmore AC, Aicher LD, Bell TA, Bradel-Tretheway B, Bryan JT, Buus RJ, Gralinski LE, Haagmans BL, McMillan L, Miller DR, Rosenzweig E, Valdar W, Wang J, Churchill GA, Threadgill DW, McWeeney SK, Katze MG, Pardo-Manuel de Villena F, Baric RS, Heise MT.
PLoS Pathog. 2013 Feb;9(2):e1003196. doi: 10.1371/journal.ppat.1003196. PMCID: PMC3585141 [ Full Text ]

High-precision genetic mapping of behavioral traits in the diversity outbred mouse population
Logan RW, Robledo RF, Recla JM, Philip VM, Bubier JA, Jay JJ, Harwood C, Wilcox T, Gatti DM, Bult CJ, Churchill GA, Chesler EJ.
Genes Brain Behav. 2013 Feb 21. doi: 10.1111/gbb.12029.

Pla2g12b and Hpn Are Genes Identified by Mouse ENU Mutagenesis That Affect HDL Cholesterol
Aljakna A, Choi S, Savage H, Hageman Blair R, Gu T, Svenson KL, Churchill GA, Hibbs M, Korstanje R.
PLoS One. 2012;7(8):e43139. PMCID: PMC3422231 [ Full Text ]

What Can Causal Networks Tell Us about Metabolic Pathways?
Blair RH, Kliebenstein DJ, Churchill GA.
PLoS Comput Biol. 2012 Apr;8(4):e1002458. PMCID: PMC3320578 [ Full Text ] [ software ]

The Diversity Outbred Mouse Population
Churchill GA, Gatti DM, Munger SC, Svenson KL
Mamm Genome. 2012 Oct;23(9-10):713-8. doi: 10.1007/s00335-012-9414-2. PMCID: PMC3524832 [ datasets ]

Discovery of novel variants in genotyping arrays improves genotype retention and reduces ascertainment bias
Didion JP, Yang H, Sheppard K, Fu CP, McMillan L, Pardo-Manuel de Villena F, Churchill GA
BMC Genomics. 2012 Jan 19;13(1):34. PMCID: PMC3305361 [ Full Text ] [ software ] [ datasets 1 ] [ datasets 2 ]

Genetic Analysis of Hematologic Parameters in Incipient Lines of the Collaborative Cross
Kelada SNP, Aylor DL, Peck BCE, Ryan JF, Tavarez U, Buus RJ, Miller DR, Chesler EJ, Threadgill DW, Churchill GA, Pardo-Manuel de Villena F, Collins FS.
G3 (Bethesda). 2012 Feb;2(2):157-65. PMCID: PMC3284323 [ Full Text ] [ datasets ]

A General Bayesian Approach to Analyzing Diallel Crosses of Inbred Strains
Lenarcic AB, Svenson KL, Churchill GA, Valdar W.
Genetics. 2012 Feb;190(2):413-35. PMCID: PMC3276624 [ Full Text ] [ datasets ] [ software ]

Adaptive evolution and effective population size in wild house mice
Phifer-Rixey M, Bonhomme F, Boursot P, Churchill GA, Piálek J, Tucker P, Nachman M.
Mol Biol Evol. 2012 Oct;29(10):2949-55. PMCID: PMC3457769 [Available on 2013/10/1] [ datasets ]

High-Resolution Genetic Mapping Using the Mouse Diversity Outbred Population
Svenson KL, Gatti DM, Valdar W, Welsh CE, Cheng R, Chesler EJ, Palmer AA, McMillan L, Churchill GA.
Genetics. 2012 Feb;190(2):437-47. PMCID: PMC3276626 [ Full Text ] [ datasets ]

Genetic analysis of albuminuria in Collaborative Cross and multiple mouse intercross populations
Thaisz J, Tsaih SW, Feng M, Philip V, Zhang Y, Yanas L, Sheehan S, Xu L, Miller DR, Paigen B, Chesler EJ, Churchill GA, Dipetrillo KJ.
Am J Physiol Renal Physiol. 2012 Oct;303(7):F972-81. PMCID: PMC3469684 [Available on 2013/10/1]

Imputation of Single-Nucleotide Polymorphisms in Inbred Mice Using Local Phylogeny
Wang JR, Pardo-Manuel de Villena F, Lawson HA, Cheverud JM, Churchill GA, McMillan L.
Genetics. 2012 Feb;190(2):449-58. PMCID: PMC3276610 [ Full Text ] [ datasets ] [ software ]

Genome-Wide Association Mapping of Quantitative Traits in Outbred Mice
Zhang W, Korstanje R, Thaisz J, Staedtler F, Harttman N, Xu L, Feng M, Yanas L, Yang H, Valdar W, Churchill GA, DiPetrillo K.
G3 (Bethesda). 2012 Feb;2(2):167-74. PMCID: PMC3284324 [ Full Text ] [ datasets ]

Uncovering Genes and Regulatory Pathways Related to Urinary Albumin Excretion
Hageman RS, Leduc MS, Caputo CR, Tsaih SW, Churchill GA, Korstanje R.
J Am Soc Nephrol. 2011 Jan;22(1):73-81. PMCID: PMC3014036 [ Full Text ] [ datasets 1 ] [ datasets 2 ]



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Project H