High-precision high-coverage functional inference from integrated data sources

<p>Abstract</p> <p>Background</p> <p>Information obtained from diverse data sources can be combined in a principled manner using various machine learning methods to increase the reliability and range of knowledge about protein function. The result is a weighted functional linkage network (FLN) in which linked neighbors share at least one function with high probability. Precision is, however, low. Aiming to provide precise functional annotation for as many proteins as possible, we explore and propose a two-step framework for functional annotation (1) construction of a high-coverage and reliable FLN via machine learning techniques (2) development of a decision rule for the constructed FLN to optimize functional annotation.</p> <p>Results</p> <p>We first apply this framework to <it>Saccharomyces cerevisiae</it>. In the first step, we demonstrate that four commonly used machine learning methods, Linear SVM, Linear Discriminant Analysis, Naïve Bayes, and Neural Network, all combine heterogeneous data to produce reliable and high-coverage FLNs, in which the linkage weight more accurately estimates functional coupling of linked proteins than use individual data sources alone. In the second step, empirical tuning of an adjustable decision rule on the constructed FLN reveals that basing annotation on maximum edge weight results in the most precise annotation at high coverages. In particular at low coverage all rules evaluated perform comparably. At coverage above approximately 50%, however, they diverge rapidly. At full coverage, the maximum weight decision rule still has a precision of approximately 70%, whereas for other methods, precision ranges from a high of slightly more than 30%, down to 3%. In addition, a scoring scheme to estimate the precisions of individual predictions is also provided. Finally, tests of the robustness of the framework indicate that our framework can be successfully applied to less studied organisms.</p> <p>Conclusion</p> <p>We provide a general two-step function-annotation framework, and show that high coverage, high precision annotations can be achieved by constructing a high-coverage and reliable FLN via data integration followed by applying a maximum weight decision rule.</p

Bayesian networks for classification, clustering, and high-dimensional data visualisation

This thesis presents new developments for a particular class of Bayesian networks which are limited in the number of parent nodes that each node in the network can have. This restriction yields structures which have low complexity (number of edges), thus enabling the formulation of optimal learning algorithms for Bayesian networks from data. The new developments are focused on three topics: classification, clustering, and high-dimensional data visualisation (topographic map formation). For classification purposes, a new learning algorithm for Bayesian networks is introduced which generates simple Bayesian network classifiers. This approach creates a completely new class of networks which previously was limited mostly to two well known models, the naive Bayesian (NB) classifier and the Tree Augmented Naive Bayes (TAN) classifier. The proposed learning algorithm enhances the NB model by adding a Bayesian monitoring system. Therefore, the complexity of the resulting network is determined according to the input data yielding structures which model the data distribution in a more realistic way which improves the classification performance. Research on Bayesian networks for clustering has not been as popular as for classification tasks. A new unsupervised learning algorithm for three types of Bayesian network classifiers, which enables them to carry out clustering tasks, is introduced. The resulting models can perform cluster assignments in a probabilistic way using the posterior probability of a data point belonging to one of the clusters. A key characteristic of the proposed clustering models, which traditional clustering techniques do not have, is the ability to show the probabilistic dependencies amongst the variables for each cluster. This feature enables a better understanding of each cluster. The final part of this thesis introduces one of the first developments for Bayesian networks to perform topographic mapping. A new unsupervised learning algorithm for the NB model is presented which enables the projection of high-dimensional data into a two-dimensional space for visualisation purposes. The Bayesian network formalism of the model allows the learning algorithm to generate a density model of the input data and the presence of a cost function to monitor the convergence during the training process. These important features are limitations which other mapping techniques have and which have been overcome in this research