There exist a large number of rare genetic diseases in humans. Our knowledge of the specific gene variants whose presence in the genome of a person predisposes them towards developing a disease, called gene associations, is incomplete. Computational tools which can predict genes which may be associated with a rare disease have great utility in healthcare. However, a majority of existing prediction algorithms require a set of already known "seed genes'' to further discover novel associations for a disease. This drawback becomes more serious for rare genetic diseases, since a large proportion do not have any known gene associations. In this work, we develop an approach for disease-gene association prediction that overcomes the reliance on seed genes. Our approach uses the similarity of the observable biological characteristics of diseases (i.e., phenotypes) along with a global map of direct and indirect human protein interactions, to transfer associations from diseases whose gene associations have been discovered to diseases with no known gene associations. We formulate disease-gene association prediction over a multimodal network of diseases and genes, and develop an approach based on graph convolutional networks. We show how our model design considerations impact prediction performance. We demonstrate that our approach outperforms simpler graph machine learning and traditional machine learning approaches, as well as a competitive network propagation based approach for the task of predicting disease-gene associations. / Master of Science / There exist a large number of rare genetic diseases in humans. Our knowledge of the specific gene variants whose presence in the genome of a person predisposes them towards developing a disease, called gene associations, is incomplete. Computational tools which can predict genes which may be associated with a rare disease have great utility in healthcare. However, a majority of existing prediction algorithms require a set of already known "seed genes'' to further discover novel associations for a disease. This drawback becomes more serious for rare genetic diseases, since a large proportion do not have any known gene associations. In this work, we develop an approach for disease-gene association prediction that overcomes the reliance on seed genes. Our approach uses the similarity of the observable biological characteristics of diseases (i.e. disease phenotypes) along with a global map of direct and indirect human protein interactions, to transfer gene associations from diseases whose gene associations have been discovered, to diseases with no known associations. We implement an approach based on the field of graph machine learning, namely graph convolutional networks, to predict the genes associated with rare genetic diseases. We show how our predictor performs, compared to other approaches, and analyze some of the choices made in the design of the predictor, along with some properties of the outputs of our predictor.
| Identifer | oai:union.ndltd.org:VTETD/oai:vtechworks.lib.vt.edu:10919/109179 |
| Date | 11 September 2020 |
| Creators | Sahasrabudhe, Dhruva Shrikrishna |
| Contributors | Computer Science, Murali, T. M., Karpatne, Anuj, Huang, Bert |
| Publisher | Virginia Tech |
| Source Sets | Virginia Tech Theses and Dissertation |
| Detected Language | English |
| Type | Thesis |
| Format | ETD, application/pdf |
| Rights | In Copyright, http://rightsstatements.org/vocab/InC/1.0/ |
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