Statistical epistasis networks reduce the computational complexity of searching three-locus genetic models

In this paper we show how building a network based on pairwise epistatic relationships can reduce the computational complexity of search for three-locus interactions. This was presented by my postdoc, Ting Hu, at the 2013 Pacific Symposium on Biocomputing.

Hu T, Andrew AS, Karagas MR, Moore JH. Statistical epistasis networks reduce the computational complexity of searching three-locus genetic models. Pac Symp Biocomput. 2013:397-408. [PubMed]

Abstract

The rapid development of sequencing technologies makes thousands to millions of genetic attributes available for testing associations with various biological traits. Searching this enormous high-dimensional data space imposes a great computational challenge in genome-wide association studies. We introduce a network-based approach to supervise the search for three-locus models of disease susceptibility. Such statistical epistasis networks (SEN) are built using strong pairwise epistatic interactions and provide a global interaction map to search for higher-order interactions by prioritizing genetic attributes clustered together in the networks. Applying this approach to a population-based bladder cancer dataset, we found a high susceptibility three-way model of genetic variations in DNA repair and immune regulation pathways, which holds great potential for studying the etiology of bladder cancer with further biological validations. We demonstrate that our SEN-supervised search is able to find a small subset of three-locus models with significantly high associations at a substantially reduced computational cost.