Development and Application of Network Algorithms for Prediction of Gene Function and Response to Viral Infection and Chemicals

The complex molecular machinery of the cell controls its response to various signals and environmental conditions. A natural approach to study these molecular mechanisms and cellular processes is with protein interaction networks. Due to the complexity of these networks, sophisticated computational techniques are required to extract biological insights from them. In this thesis, I develop and apply network-based algorithms for three different challenges. 1. I develop a novel, highly-scalable algorithm for network-based label prediction methods that enables the integration of functional annotations and interaction networks across many species in order to predict the functions of genes in newly-sequenced bacteria. 2. To overcome the limitations of experimental approaches to find human proteins and processes that are hijacked by SARS-CoV-2, I adapt network propagation approaches for predicting human interactors of the virus. 3. Large-scale experimental techniques to screen chemicals for toxicity have tested their effects on many individual proteins. I integrate human protein-protein interactions with this data to gain insights into the molecular networks those chemicals affect. For each of these research problems, I perform comprehensive evaluations and downstream analyses to demonstrate both the accuracy of our approaches and their utility in obtaining a broader understanding of the molecular systems in question.

Name thesis:degree_name

Doctor of Philosophy

Level thesis:degree_level

doctoral

Discipline thesis:degree_discipline

Genetics, Bioinformatics, and Computational Biology

Department dc:contributor.department

Genetics, Bioinformatics, and Computational Biology

Grantor dc:publisher

Virginia Tech

Year dc:date.issued

2020

Author dc:creator

• Law, Jeffrey Norman

Chair dc:contributor.committeechair

• Murali, T. M.

Committee members dc:contributor.committeemember

• Rajagopalan, Padmavathy
• Heath, Lenwood S.
• Kale, Shiv Dutt

• Network Propagation
• Gene Function Prediction
• SARS-CoV-2
• Cellular Signaling

Statement dc:rights

• In Copyright

Licence dc:rights.uri

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

Dc Identifier Other

vt_gsexam:28071

OAI identifier oai:identifier

oai:vtechworks.lib.vt.edu:10919/110406