Prediction of deleterious mutations in coding regions of mammals with transfer learning

Abstract

The genomes of mammals contain thousands of deleterious mutations. It is important to be able to recognize them with high precision. In conservation biology, the small size of fragmented populations results in accumulation of damaging variants. Preserving animals with less damaged genomes could optimize conservation efforts. In breeding of farm animals, trade-offs between farm performance versus general fitness might be better avoided if deleterious mutations are well classified. In humans, the problem of such a precise classification has been successfully solved, in large part due to large databases of disease-causing mutations. However, this kind of information is very limited for other mammals. Here, we propose to better use information available on human mutations to enable classification of damaging mutations in other mammalian species. Specifically, we apply transfer learning—machine learning methods—improving small dataset for solving a focal problem (recognizing damaging mutations in our companion and farm animals) due to the use of much large datasets available for solving a related problem (recognizing damaging mutations in humans). We validate our tools using mouse and dog annotated datasets and obtain significantly better results in companion to the SIFT classifier. Then, we apply them to predict deleterious mutations in cattle genomewide dataset.