ON APPLICATIONS OF STATISTICAL LEARNING TO BIOPHYSICS

In this dissertation, we develop statistical and machine learning methods for problems in biological systems and processes. In particular, we are interested in two problems–predicting structural properties for membrane proteins and clustering genes based on microarray experiments. In the membrane protein problem, we introduce a compact representation for amino acids, and build a neural network predictor based on it to identify transmembrane domains for membrane proteins. Membrane proteins are divided into two classes based on the secondary structure of the parts spanning the bilayer lipids: alpha-helical and beta-barrel membrane proteins. We further build a support regression model to predict the lipid exposed levels for the amino acids within the transmembrane domains in alpha-helical membrane proteins. We also develop methods to predict pore-forming residues for beta-barrel membrane proteins. In the other problem, we apply a context-specific Bayesian clustering model to cluster genes based on their expression levels and cDNA copy numbers. This dissertation is organized as follows. Chapter 1 introduces the most relevant biology and statistical and machine learning methods. Chapters 2 and 3 focus on prediction of transmembrane domains for the alpha-helix and the beta-barrel, respectively. Chapter 4 discusses the prediction of relative lipid accessibility, a different structural property for membrane proteins. The final chapter addresses the gene clustering approach.