Graph-based Regularization in Machine Learning: Discovering Driver Modules in Biological Networks

Author

Xi GaoFollow

DOI

https://doi.org/10.25772/2943-T286

Defense Date

2015

Document Type

Dissertation

Degree Name

Doctor of Philosophy

Department

Computer Science

First Advisor

Tomasz Arodz

Abstract

Curiosity of human nature drives us to explore the origins of what makes each of us different. From ancient legends and mythology, Mendel's law, Punnett square to modern genetic research, we carry on this old but eternal question. Thanks to technological revolution, today's scientists try to answer this question using easily measurable gene expression and other profiling data. However, the exploration can easily get lost in the data of growing volume, dimension, noise and complexity. This dissertation is aimed at developing new machine learning methods that take data from different classes as input, augment them with knowledge of feature relationships, and train classification models that serve two goals: 1) class prediction for previously unseen samples; 2) knowledge discovery of the underlying causes of class differences. Application of our methods in genetic studies can help scientist take advantage of existing biological networks, generate diagnosis with higher accuracy, and discover the driver networks behind the differences. We proposed three new graph-based regularization algorithms. Graph Connectivity Constrained AdaBoost algorithm combines a connectivity module, a deletion function, and a model retraining procedure with the AdaBoost classifier. Graph-regularized Linear Programming Support Vector Machine integrates penalty term based on submodular graph cut function into linear classifier's objective function. Proximal Graph LogisticBoost adds lasso and graph-based penalties into logistic risk function of an ensemble classifier. Results of tests of our models on simulated biological datasets show that the proposed methods are able to produce accurate, sparse classifiers, and can help discover true genetic differences between phenotypes.

Rights

© The Author

Is Part Of

VCU University Archives

Is Part Of

VCU Theses and Dissertations

Date of Submission

8-1-2015