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Open Access Highly Accessed Methodology article

Learning genetic epistasis using Bayesian network scoring criteria

Xia Jiang1*, Richard E Neapolitan5, M Michael Barmada4 and Shyam Visweswaran123

Author Affiliations

1 Department of Biomedical Informatics, University of Pittsburgh, Pittsburgh, PA, USA

2 Intelligent Systems Program, University of Pittsburgh, Pittsburgh, PA, USA

3 Clinical and Translational Science Institute, University Pittsburgh, Pittsburgh, PA, USA

4 Department of Human Genetics, University of Pittsburgh, Pittsburgh, PA, USA

5 Department of Computer Science, Northeastern Illinois University, Chicago, IL, USA

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BMC Bioinformatics 2011, 12:89  doi:10.1186/1471-2105-12-89

Published: 31 March 2011

Abstract

Background

Gene-gene epistatic interactions likely play an important role in the genetic basis of many common diseases. Recently, machine-learning and data mining methods have been developed for learning epistatic relationships from data. A well-known combinatorial method that has been successfully applied for detecting epistasis is Multifactor Dimensionality Reduction (MDR). Jiang et al. created a combinatorial epistasis learning method called BNMBL to learn Bayesian network (BN) epistatic models. They compared BNMBL to MDR using simulated data sets. Each of these data sets was generated from a model that associates two SNPs with a disease and includes 18 unrelated SNPs. For each data set, BNMBL and MDR were used to score all 2-SNP models, and BNMBL learned significantly more correct models. In real data sets, we ordinarily do not know the number of SNPs that influence phenotype. BNMBL may not perform as well if we also scored models containing more than two SNPs. Furthermore, a number of other BN scoring criteria have been developed. They may detect epistatic interactions even better than BNMBL.

Although BNs are a promising tool for learning epistatic relationships from data, we cannot confidently use them in this domain until we determine which scoring criteria work best or even well when we try learning the correct model without knowledge of the number of SNPs in that model.

Results

We evaluated the performance of 22 BN scoring criteria using 28,000 simulated data sets and a real Alzheimer's GWAS data set. Our results were surprising in that the Bayesian scoring criterion with large values of a hyperparameter called α performed best. This score performed better than other BN scoring criteria and MDR at recall using simulated data sets, at detecting the hardest-to-detect models using simulated data sets, and at substantiating previous results using the real Alzheimer's data set.

Conclusions

We conclude that representing epistatic interactions using BN models and scoring them using a BN scoring criterion holds promise for identifying epistatic genetic variants in data. In particular, the Bayesian scoring criterion with large values of a hyperparameter α appears more promising than a number of alternatives.