Skip to main content
Grant Details

Grant Number: 5P01CA196569-03 Interpret this number
Primary Investigator: Thomas, Duncan
Organization: University Of Southern California
Project Title: Statistical Methods for Integrative Genomics in Cancer
Fiscal Year: 2018
Back to top


Abstract

?DESCRIPTION (provided by applicant): We aim to develop novel statistical methods to address some of the major problems facing cancer genetic epidemiologists in the "post-GWAS" era and to illustrate their use for discovery of novel biology in various colorectal cancer (CRC) studies. These methods leverage prior biological knowledge to inform integrative genomics analyses (Project 1), use phylogenetic information to infer gene function as inputs to our epidemiologic modeling projects (Project 2), model the role of the microbiome and the exposome in cancer risk (Project 3), and exploit intra-tumor heterogeneity to learn about somatic tumor evolution and how this process is modified by the internal environment (Project 4). These four projects will be supported by an administrative core and three shared resource cores on functional annotation, high performance computing, and software development. The entire program is motivated by an overall objective of providing tools for evaluating the impact of potential preventive or therapeutic interventions based on modifiable risk factors. Specifically, the aims of the overall program are (1) to develop statistical analysis methods to integrate multiple types of omics data that describe both constitutional and acquired genomic variation as well as measures of the external and internal environment into comprehensive risk prediction models, leveraging external information; (2) to apply these methods to various studies of CRC etiology and prognosis to uncover novel associations and to develop predictive models that would have translational significance for possible primary, secondary, and tertiary interventions; and (3) to establish an infrastructure (administrative, bioinformatic, computational, software) to support the various research projects and facilitate making our methods accessible to the broader scientific community. This will be achieved by a combination of theoretical developments, simulation studies closely keyed to real data projects, applications to several studies of CRC, and distribution of software for use by outside investigators. Beyond applications to colorectal cancer, our methods will be broadly applicable to other cancer types and many other chronic diseases.

Back to top


Publications

Epigenetic Heterogeneity in Human Colorectal Tumors Reveals Preferential Conservation And Evidence of Immune Surveillance.
Authors: Ryser M.D. , Yu M. , Grady W. , Siegmund K. , Shibata D. .
Source: Scientific Reports, 2018-11-23 00:00:00.0; 8(1), p. 17292.
EPub date: 2018-11-23 00:00:00.0.
PMID: 30470817
Related Citations

Using Bayes model averaging to leverage both gene main effects and G?×? E interactions to identify genomic regions in genome-wide association studies.
Authors: Moss L.C. , Gauderman W.J. , Lewinger J.P. , Conti D.V. .
Source: Genetic Epidemiology, 2018-11-19 00:00:00.0; , .
EPub date: 2018-11-19 00:00:00.0.
PMID: 30456811
Related Citations

Data integration by multi-tuning parameter elastic net regression.
Authors: Liu J. , Liang G. , Siegmund K.D. , Lewinger J.P. .
Source: Bmc Bioinformatics, 2018-10-10 00:00:00.0; 19(1), p. 369.
EPub date: 2018-10-10 00:00:00.0.
PMID: 30305021
Related Citations

Somatic cell evolution: how to improve with age.
Authors: Shibata D. .
Source: The Journal Of Pathology, 2018-09-23 00:00:00.0; , .
EPub date: 2018-09-23 00:00:00.0.
PMID: 30246391
Related Citations

Spatial mutation patterns as markers of early colorectal tumor cell mobility.
Authors: Ryser M.D. , Min B.H. , Siegmund K.D. , Shibata D. .
Source: Proceedings Of The National Academy Of Sciences Of The United States Of America, 2018-05-29 00:00:00.0; 115(22), p. 5774-5779.
EPub date: 2018-05-14 00:00:00.0.
PMID: 29760052
Related Citations

Targeted sequencing of established and candidate colorectal cancer genes in the Colon Cancer Family Registry Cohort.
Authors: Raskin L. , Guo Y. , Du L. , Clendenning M. , Rosty C. , Colon Cancer Family Registry (CCFR) , Lindor N.M. , Gruber S.B. , Buchanan D.D. .
Source: Oncotarget, 2017-11-07 00:00:00.0; 8(55), p. 93450-93463.
EPub date: 2017-06-21 00:00:00.0.
PMID: 29212164
Related Citations

Lessons Learned From Past Gene-Environment Interaction Successes.
Authors: Ritz B.R. , Chatterjee N. , Garcia-Closas M. , Gauderman W.J. , Pierce B.L. , Kraft P. , Tanner C.M. , Mechanic L.E. , McAllister K. .
Source: American Journal Of Epidemiology, 2017-10-01 00:00:00.0; 186(7), p. 778-786.
PMID: 28978190
Related Citations

Incorporation of Biological Knowledge Into the Study of Gene-Environment Interactions.
Authors: Ritchie M.D. , Davis J.R. , Aschard H. , Battle A. , Conti D. , Du M. , Eskin E. , Fallin M.D. , Hsu L. , Kraft P. , et al. .
Source: American Journal Of Epidemiology, 2017-10-01 00:00:00.0; 186(7), p. 771-777.
PMID: 28978191
Related Citations

Update on the State of the Science for Analytical Methods for Gene-Environment Interactions.
Authors: Gauderman W.J. , Mukherjee B. , Aschard H. , Hsu L. , Lewinger J.P. , Patel C.J. , Witte J.S. , Amos C. , Tai C.G. , Conti D. , et al. .
Source: American Journal Of Epidemiology, 2017-10-01 00:00:00.0; 186(7), p. 762-770.
PMID: 28978192
Related Citations

Current Challenges and New Opportunities for Gene-Environment Interaction Studies of Complex Diseases.
Authors: McAllister K. , Mechanic L.E. , Amos C. , Aschard H. , Blair I.A. , Chatterjee N. , Conti D. , Gauderman W.J. , Hsu L. , Hutter C.M. , et al. .
Source: American Journal Of Epidemiology, 2017-10-01 00:00:00.0; 186(7), p. 753-761.
PMID: 28978193
Related Citations

Opportunities and Challenges for Environmental Exposure Assessment in Population-Based Studies.
Authors: Patel C.J. , Kerr J. , Thomas D.C. , Mukherjee B. , Ritz B. , Chatterjee N. , Jankowska M.M. , Madan J. , Karagas M.R. , McAllister K.A. , et al. .
Source: Cancer Epidemiology, Biomarkers & Prevention : A Publication Of The American Association For Cancer Research, Cosponsored By The American Society Of Preventive Oncology, 2017-07-14 00:00:00.0; , .
EPub date: 2017-07-14 00:00:00.0.
PMID: 28710076
Related Citations

Estimating the Effect of Targeted Screening Strategies: An Application to Colonoscopy and Colorectal Cancer.
Authors: Thomas D.C. .
Source: Epidemiology (cambridge, Mass.), 2017 Jul; 28(4), p. 470-478.
PMID: 28368944
Related Citations

Multiancestry Study of Gene-Lifestyle Interactions for Cardiovascular Traits in 610 475 Individuals From 124 Cohorts: Design and Rationale.
Authors: Rao D.C. , Sung Y.J. , Winkler T.W. , Schwander K. , Borecki I. , Cupples L.A. , Gauderman W.J. , Rice K. , Munroe P.B. , Psaty B.M. , et al. .
Source: Circulation. Cardiovascular Genetics, 2017 Jun; 10(3), .
PMID: 28620071
Related Citations

Genome-Wide Interaction Analysis of Air Pollution Exposure and Childhood Asthma with Functional Follow-up.
Authors: Gref A. , Merid S.K. , Gruzieva O. , Ballereau S. , Becker A. , Bellander T. , Bergström A. , Bossé Y. , Bottai M. , Chan-Yeung M. , et al. .
Source: American Journal Of Respiratory And Critical Care Medicine, 2017-05-15 00:00:00.0; 195(10), p. 1373-1383.
PMID: 27901618
Related Citations

Inclusion Of Biological Knowledge In A Bayesian Shrinkage Model For Joint Estimation Of Snp Effects
Authors: Pereira M. , Thompson J.R. , Weichenberger C.X. , Thomas D.C. , Minelli C. .
Source: Genetic Epidemiology, 2017-04-10 00:00:00.0; , .
PMID: 28393391
Related Citations

What Does "Precision Medicine" Have to Say About Prevention?
Authors: Thomas D.C. .
Source: Epidemiology (cambridge, Mass.), 2017-03-29 00:00:00.0; , .
EPub date: 2017-03-29 00:00:00.0.
PMID: 28368942
Related Citations

Informatics and Data Analytics to Support Exposome-Based Discovery for Public Health.
Authors: Manrai A.K. , Cui Y. , Bushel P.R. , Hall M. , Karakitsios S. , Mattingly C.J. , Ritchie M. , Schmitt C. , Sarigiannis D.A. , Thomas D.C. , et al. .
Source: Annual Review Of Public Health, 2017-03-20 00:00:00.0; 38, p. 279-294.
EPub date: 2016-12-23 00:00:00.0.
PMID: 28068484
Related Citations

Cross-Species Transcriptome Profiling Identifies New Alveolar Epithelial Type I Cell-Specific Genes.
Authors: Marconett C.N. , Zhou B. , Sunohara M. , Pouldar T.M. , Wang H. , Liu Y. , Rieger M.E. , Tran E. , Flodby P. , Siegmund K.D. , et al. .
Source: American Journal Of Respiratory Cell And Molecular Biology, 2017 Mar; 56(3), p. 310-321.
PMID: 27749084
Related Citations

Improving needle biopsy accuracy in small renal mass using tumor-specific DNA methylation markers.
Authors: Chopra S. , Liu J. , Alemozaffar M. , Nichols P.W. , Aron M. , Weisenberger D.J. , Collings C.K. , Syan S. , Hu B. , Desai M. , et al. .
Source: Oncotarget, 2017-01-17 00:00:00.0; 8(3), p. 5439-5448.
PMID: 27690297
Related Citations

Gene Expression Profiling in Blood Provides Reproducible Molecular Insights into Asthma Control.
Authors: Croteau-Chonka D.C. , Qiu W. , Martinez F.D. , Strunk R.C. , Lemanske R.F. , Liu A.H. , Gilliland F.D. , Millstein J. , Gauderman W.J. , Ober C. , et al. .
Source: American Journal Of Respiratory And Critical Care Medicine, 2017-01-15 00:00:00.0; 195(2), p. 179-188.
PMID: 27494826
Related Citations

Expansion of the Gene Ontology knowledgebase and resources.
Authors: The Gene Ontology Consortium .
Source: Nucleic Acids Research, 2017-01-04 00:00:00.0; 45(D1), p. D331-D338.
EPub date: 2017-01-04 00:00:00.0.
PMID: 27899567
Related Citations

PANTHER version 11: expanded annotation data from Gene Ontology and Reactome pathways, and data analysis tool enhancements.
Authors: Mi H. , Huang X. , Muruganujan A. , Tang H. , Mills C. , Kang D. , Thomas P.D. .
Source: Nucleic Acids Research, 2017-01-04 00:00:00.0; 45(D1), p. D183-D189.
EPub date: 2017-01-04 00:00:00.0.
PMID: 27899595
Related Citations

The Gene Ontology and the Meaning of Biological Function.
Authors: Thomas P.D. .
Source: Methods In Molecular Biology (clifton, N.j.), 2017; 1446, p. 15-24.
PMID: 27812932
Related Citations

An evaluation of processing methods for HumanMethylation450 BeadChip data.
Authors: Liu J. , Siegmund K.D. .
Source: Bmc Genomics, 2016-06-22 00:00:00.0; 17, p. 469.
EPub date: 2016-06-22 00:00:00.0.
PMID: 27334613
Related Citations

Identification of DNA Methylation-Independent Epigenetic Events Underlying Clear Cell Renal Cell Carcinoma.
Authors: Becket E. , Chopra S. , Duymich C.E. , Lin J.J. , You J.S. , Pandiyan K. , Nichols P.W. , Siegmund K.D. , Charlet J. , Weisenberger D.J. , et al. .
Source: Cancer Research, 2016-04-01 00:00:00.0; 76(7), p. 1954-64.
EPub date: 2016-04-01 00:00:00.0.
PMID: 26759245
Related Citations

Increased yield of actionable mutations using multi-gene panels to assess hereditary cancer susceptibility in an ethnically diverse clinical cohort.
Authors: Ricker C. , Culver J.O. , Lowstuter K. , Sturgeon D. , Sturgeon J.D. , Chanock C.R. , Gauderman W.J. , McDonnell K.J. , Idos G.E. , Gruber S.B. .
Source: Cancer Genetics, 2016 Apr; 209(4), p. 130-7.
PMID: 26908360
Related Citations

At least two well-spaced samples are needed to genotype a solid tumor.
Authors: Siegmund K. , Shibata D. .
Source: Bmc Cancer, 2016-03-25 00:00:00.0; 16, p. 250.
EPub date: 2016-03-25 00:00:00.0.
PMID: 27015839
Related Citations

GWASeq: targeted re-sequencing follow up to GWAS.
Authors: Salomon M.P. , Li W.L. , Edlund C.K. , Morrison J. , Fortini B.K. , Win A.K. , Conti D.V. , Thomas D.C. , Duggan D. , Buchanan D.D. , et al. .
Source: Bmc Genomics, 2016-03-03 00:00:00.0; 17, p. 176.
EPub date: 2016-03-03 00:00:00.0.
PMID: 26940994
Related Citations

Adaptive Set-Based Methods for Association Testing.
Authors: Su Y.C. , Gauderman W.J. , Berhane K. , Lewinger J.P. .
Source: Genetic Epidemiology, 2016 Feb; 40(2), p. 113-22.
PMID: 26707371
Related Citations

Detecting Gene-Environment Interactions for a Quantitative Trait in a Genome-Wide Association Study.
Authors: Zhang P. , Lewinger J.P. , Conti D. , Morrison J.L. , Gauderman W.J. .
Source: Genetic Epidemiology, 2016 07; 40(5), p. 394-403.
PMID: 27230133
Related Citations

An Empirical Comparison of Joint and Stratified Frameworks for Studying G × E Interactions: Systolic Blood Pressure and Smoking in the CHARGE Gene-Lifestyle Interactions Working Group.
Authors: Sung Y.J. , Winkler T.W. , Manning A.K. , Aschard H. , Gudnason V. , Harris T.B. , Smith A.V. , Boerwinkle E. , Brown M.R. , Morrison A.C. , et al. .
Source: Genetic Epidemiology, 2016 07; 40(5), p. 404-15.
PMID: 27230302
Related Citations

Large-scale inference of gene function through phylogenetic annotation of Gene Ontology terms: case study of the apoptosis and autophagy cellular processes.
Authors: Feuermann M. , Gaudet P. , Mi H. , Lewis S.E. , Thomas P.D. .
Source: Database : The Journal Of Biological Databases And Curation, 2016; 2016, .
PMID: 28025345
Related Citations




Back to Top