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Machine Learning & Data Mining

Clinical Decision Support

Genomics of

Complex Diseases

Human Behavior Analysis

Jinbo Bi Computer Science and Engineering Department

University of ConnecticutEmail: jinbo@engr.uconn.edu

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Genetics of Complex Diseases

Complex phenotypes

Mixture of

heterogeneous subtypes

Causes

Genetic heterogeneity,

gene-environment

difficult to correlate

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Our project: Identify phenotypic subtypes and subtype-dependent genetic variants

Variance

analysis

Variance

analysis

Predictive

modeling

Association analysis

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Subtyping Method Helps  SNP ID Gene

P-value

CD diagnosis Subtype 4 Subtype 5

AA

rs5988072 HTR2C 8.04E-06** a 2.42E-04 5.89E-05* a

rs11143429 ALDH1A1 3.35E-04 a 2.34E-03 1.53E-03

rs11939815 CLOCK 4.00E-043.87E-05**

a2.52E-02

rs991738 GLRA1 5.72E-04 3.02E-04 a 3.59E-02

rs3805155 CLOCK 6.05E-04 1.11E-04 a 3.17E-02

rs13116194 CLOCK 7.57E-04 2.11E-04 a 3.18E-02

rs6850524 CLOCK 1.37E-03 2.01E-04 a 3.42E-02

rs3761248 OXT 3.27E-03 5.19E-03 3.04E-04 a

EA rs363256 SLC18A2 7.68E-03 2.27E-04 a 2.86E-02

Based on 9,436 subjects, 68 clinical features and 130 candidate genes ( 1,400 SNPs)

Subtype 4 – Heavy cocaine use, infrequent intravenous injection groupSubtype 5 – Early-onset, heavy cocaine use, high comorbidity group

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References Genomewide association study of opioid dependence and related traits: multiple associations mapped to calcium and potassium pathways. Joel Gelernter, Henry R. Kranzler, Richard Sherva, Ryan Koesterer, Jiangwen Sun, Jinbo Bi, Laura Almasy, Hongyu Zhao, Lindsay A. Farrer. In revision of PLoS Genetics, 2013.

Comparing the Utility of Homogeneous Subtypes of Cocaine Use and Related Behaviors with DSM-IV Cocaine Dependence as Traits for Association Analysis. Jinbo Bi, Joel Gelernter, Jiangwen Sun and Henry R. Kranzler. To appear in American Journal of Medical Genetics (Part B), 2013.

Improved methods to identify stable, highly heritable subtypes of opioid use and related behaviors. Jiangwen Sun, Jinbo Bi, Grace Chan, David Oslin, Lindsay Farrer, Joel Gelernter and Henry R. Kranzler. Addictive Behavior, 2012.

Multi-view Co-modeling to Improve Genetic Association of Complex Disease Phenotypes. Jiangwen Sun, Jinbo Bi and Henry R. Kranzler. To appear in IEEE Journal of Biomedical and Health Informatics, 2013.

Multi-view Biclustering for Genotype-Phenotype Association Studies of Complex Diseases. Jiangwen Sun, Jinbo Bi and Henry R. Kranzler. Submitted to IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2013.

A Multi-Objective Program for Quantitative Subtyping of Clinically Relevant Phenotypes. Jiangwen Sun, Jinbo Bi and Henry R. Kranzler. IEEE International Conference on Bioinformatics and Biomedicine (BIBM), 2012.