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Bioinformatics Advance Access published online on June 22, 2007
Bioinformatics, doi:10.1093/bioinformatics/btm317
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© The Author (2007). Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

Evaporative cooling feature selection for genotypic data involving interactions

B. A. McKinney a,*, D. M. Reif b, B. C. White c, J. E. Crowe, Jr. d and J. H. Moore c

aDepartment of Genetics, University of Alabama School of Medicine, Birmingham, AL 35294
bNational Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, NC 27711
cComputational Genetics Laboratory, Department of Genetics, Dartmouth Medical School, Lebanon, NH 03756
dProgram in Vaccine Sciences, Departments of Microbiology and Immunology, and Pediatrics, Vanderbilt University Medical Center, Nashville, TN 37232

*to whom correspondence should be addressed. Dr. Brett McKinney, E-mail: bmckinney{at}genetics.uab.edu


  Abstract

Motivation: The development of genome-wide capabilities for genotyping has led to the practical problem of identifying the minimum subset of genetic variants relevant to the classification of a phenotype. This challenge is especially difficult in the presence of attribute interactions, noise, and small sample size.

Methods: Analogous to the physical mechanism of evaporation, we introduce an evaporative cooling (EC) feature selection algorithm that seeks to obtain a subset of attributes with the optimum information temperature (i.e., the least noise). EC uses an attribute quality measure analogous to thermodynamic free energy that combines Relief-F and mutual information to evaporate (i.e., remove) noise features, leaving behind a subset of attributes that contain DNA sequence variations associated with a given phenotype.

Methods: EC is able to identify functional sequence variations that involve interactions (epistasis) between other sequence variations that influence their association with the phenotype. This ability is demonstrated on simulated genotypic data with attribute interactions and on real genotypic data from individuals who experienced adverse events following smallpox vaccination. The EC formalism allows us to combine information entropy, energy and temperature into a single information free energy attribute quality measure that balances interaction and main effects.

Availability: Open source software, written in Java, is freely available upon request.

Associate Editor: Prof. Keith Crandall

Received on May 2, 2007; revised on May 2, 2007; accepted on June 6, 2007

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