Background: Schizophrenia and autism are examples of polygenic diseases caused by a multitude of genetic variants, many of which are still poorly understood. Recently, both diseases have been associated with disrupted neuron motility and migration patterns, suggesting that aberrant cell motility is a phenotype for these neurological diseases. Results: We formulate the Polygenic Disease Phenotype Problem which seeks to identify candidate disease genes that may be associated with a phenotype such as cell motility. We present a machine learning approach to solve this problem for schizophrenia and autism genes within a brain-specific functional interaction network. Our method outperforms peer semi-supervised learning approaches, achieving better cross-validation accuracy across different sets of gold-standard positives. We identify top candidates for both schizophrenia and autism, and select six genes labeled as schizophrenia positives that are predicted to be associated with cell motility for follow-up experiments. Conclusions: Candidate genes predicted by our method suggest testable hypotheses about these genes-role in cell motility regulation, offering a framework for generating predictions for experimental validation.
CITATION STYLE
Bern, M., King, A., Applewhite, D. A., & Ritz, A. (2019). Network-based prediction of polygenic disease genes involved in cell motility. BMC Bioinformatics, 20. https://doi.org/10.1186/s12859-019-2834-1
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