Artificial Immune Systems for Epistasis Analysis in Human Genetics

摘要

Modern genotyping techniques have allowed the field of human genetics to generate vast amounts of data, but analysis methodologies have not been able to keep pace with this increase. In order to allow personal genomics to play a vital role in modern health care, analysis methods capable of discovering high order interactions that contribute to an individual's risk of disease must be developed. An artificial immune system (AIS) is a method which maps well to this problem and has a number of appealing properties. By considering many attributes simultaneously, it may be able to effectively and efficiently detect epistasis, that is non-additive gene-gene interactions. This situation of interacting genes is currently very difficult to detect without biological insight or statistical heuristics. Even with these approaches, at low heritability (i.e. where there is only a small genetic signal), these approaches have trouble distinguishing genetic signal from noise. The AIS also has a compact solution representation which can be rapidly evaluated. Finally the AIS approach, by iteratively developing an antibody which ignores irrelevant genotypes, may be better able to differentiate signal from noise than machine learning approaches like ReliefF which struggle at small heritabilities. Here we develop a basic AIS and evaluate it on very low heritability datasets. We find that the basic AIS is not robust to parameter settings but that, at some parameter settings, it performs very effectively. We use the settings where the strategy succeeds to suggest a path towards a robust AIS for human genetics. Developing an AIS which succeeds across many parameter settings will be critical to prepare this method for widespread use.