Probabilistic Graphical Models and Algorithms for

Abstract

In this thesis I present research in two fields: machine learning and computational biology.

First, I develop new machine learning methods for graphical models that can be applied to protein problems. Then I apply graphical model algorithms to protein problems, obtaining improvements in protein structure prediction and protein structure alignment. First,in the machine learning work, I focus on a special kind of graphical model---conditional random fields (CRFs). Here, I present a new semi-supervised training procedure for CRFs that can be used to train sequence segmentors and labellers from a combination of labeled and unlabeled training data. Such learning algorithms can be applied to protein and gene name entity recognition problems. This work provides one of the first semi-supervised discriminative training methods for structured classification.

Second, in my computational biology work, I focus mainly on protein problems. In particular, I first propose a tree decomposition method for solving the protein structure prediction and protein structure alignment problems. In so doing, I reveal why tree decomposition is a good method for many protein problems. Then, I propose a computational framework for detection of similar structures of a target protein with sparse NMR data, which can help to predict protein structure using experimental data.

Finally, I propose a new machine learning approach---LS_Boost---to solve the protein fold recognition problem, which is one of the key steps in protein structure prediction. After a thorough comparison, the algorithm is proved to be both more accurate and more efficient than traditional z-Score method and other machine learning methods.