A Multimodal Graph Convolutional Approach to Predict Genes Associated with Rare Genetic Diseases

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.

Name thesis:degree_name

Master of Science

Level thesis:degree_level

masters

Discipline thesis:degree_discipline

Computer Science and Applications

Department dc:contributor.department

Computer Science

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2020

Author dc:creator

• Sahasrabudhe, Dhruva Shrikrishna

Chair dc:contributor.committeechair

• Murali, T. M.

Committee members dc:contributor.committeemember

• Karpatne, Anuj
• Huang, Bert

• Graph Machine Learning
• Disease Gene Prediction
• Graph Convolutional Networks
• Link Prediction
• Multimodal Networks

Statement dc:rights

• In Copyright

Licence dc:rights.uri

• http://rightsstatements.org/vocab/InC/1.0/

Dc Identifier Other

vt_gsexam:27383

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/109179