Probabilistic Graphical Models and Algorithms for

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

Identification of functionally related enzymes by learning-to-rank methods

Enzyme sequences and structures are routinely used in the biological sciences as queries to search for functionally related enzymes in online databases. To this end, one usually departs from some notion of similarity, comparing two enzymes by looking for correspondences in their sequences, structures or surfaces. For a given query, the search operation results in a ranking of the enzymes in the database, from very similar to dissimilar enzymes, while information about the biological function of annotated database enzymes is ignored. In this work we show that rankings of that kind can be substantially improved by applying kernel-based learning algorithms. This approach enables the detection of statistical dependencies between similarities of the active cleft and the biological function of annotated enzymes. This is in contrast to search-based approaches, which do not take annotated training data into account. Similarity measures based on the active cleft are known to outperform sequence-based or structure-based measures under certain conditions. We consider the Enzyme Commission (EC) classification hierarchy for obtaining annotated enzymes during the training phase. The results of a set of sizeable experiments indicate a consistent and significant improvement for a set of similarity measures that exploit information about small cavities in the surface of enzymes

Applicability of semi-supervised learning assumptions for gene ontology terms prediction

Gene Ontology (GO) is one of the most important resources in bioinformatics, aiming to provide a unified framework for the biological annotation of genes and proteins across all species. Predicting GO terms is an essential task for bioinformatics, but the number of available labelled proteins is in several cases insufficient for training reliable machine learning classifiers. Semi-supervised learning methods arise as a powerful solution that explodes the information contained in unlabelled data in order to improve the estimations of traditional supervised approaches. However, semi-supervised learning methods have to make strong assumptions about the nature of the training data and thus, the performance of the predictor is highly dependent on these assumptions. This paper presents an analysis of the applicability of semi-supervised learning assumptions over the specific task of GO terms prediction, focused on providing judgment elements that allow choosing the most suitable tools for specific GO terms. The results show that semi-supervised approaches significantly outperform the traditional supervised methods and that the highest performances are reached when applying the cluster assumption. Besides, it is experimentally demonstrated that cluster and manifold assumptions are complimentary to each other and an analysis of which GO terms can be more prone to be correctly predicted with each assumption, is provided.Postprint (published version

Transforming Graph Representations for Statistical Relational Learning

Relational data representations have become an increasingly important topic due to the recent proliferation of network datasets (e.g., social, biological, information networks) and a corresponding increase in the application of statistical relational learning (SRL) algorithms to these domains. In this article, we examine a range of representation issues for graph-based relational data. Since the choice of relational data representation for the nodes, links, and features can dramatically affect the capabilities of SRL algorithms, we survey approaches and opportunities for relational representation transformation designed to improve the performance of these algorithms. This leads us to introduce an intuitive taxonomy for data representation transformations in relational domains that incorporates link transformation and node transformation as symmetric representation tasks. In particular, the transformation tasks for both nodes and links include (i) predicting their existence, (ii) predicting their label or type, (iii) estimating their weight or importance, and (iv) systematically constructing their relevant features. We motivate our taxonomy through detailed examples and use it to survey and compare competing approaches for each of these tasks. We also discuss general conditions for transforming links, nodes, and features. Finally, we highlight challenges that remain to be addressed

Mean-Field Theory of Meta-Learning

We discuss here the mean-field theory for a cellular automata model of meta-learning. The meta-learning is the process of combining outcomes of individual learning procedures in order to determine the final decision with higher accuracy than any single learning method. Our method is constructed from an ensemble of interacting, learning agents, that acquire and process incoming information using various types, or different versions of machine learning algorithms. The abstract learning space, where all agents are located, is constructed here using a fully connected model that couples all agents with random strength values. The cellular automata network simulates the higher level integration of information acquired from the independent learning trials. The final classification of incoming input data is therefore defined as the stationary state of the meta-learning system using simple majority rule, yet the minority clusters that share opposite classification outcome can be observed in the system. Therefore, the probability of selecting proper class for a given input data, can be estimated even without the prior knowledge of its affiliation. The fuzzy logic can be easily introduced into the system, even if learning agents are build from simple binary classification machine learning algorithms by calculating the percentage of agreeing agents.Comment: 23 page

Kernel methods in genomics and computational biology

Support vector machines and kernel methods are increasingly popular in genomics and computational biology, due to their good performance in real-world applications and strong modularity that makes them suitable to a wide range of problems, from the classification of tumors to the automatic annotation of proteins. Their ability to work in high dimension, to process non-vectorial data, and the natural framework they provide to integrate heterogeneous data are particularly relevant to various problems arising in computational biology. In this chapter we survey some of the most prominent applications published so far, highlighting the particular developments in kernel methods triggered by problems in biology, and mention a few promising research directions likely to expand in the future