MOTIVATION: Functional genomics data provides a rich source of information that can be used in the annotation of the thousands of genes of unknown function found in most sequenced genomes. However, previous gene function prediction programs are mostly produced for relatively well-annotated organisms that often have a large amount of functional genomics data. Here, we present a novel method for predicting gene function that uses clustering of genes by semantic similarity, a naïve Bayes classifier and 'enrichment analysis' to predict gene function for a genome that is less well annotated but does has a severe effect on human health, that of the malaria parasite Plasmodium falciparum. RESULTS: Predictions for the molecular function, biological process and cellular component of P.falciparum genes were created from eight different datasets with a combined prediction also being produced. The high-confidence predictions produced by the combined prediction were compared to those produced by a simple K-nearest neighbour classifier approach and were shown to improve accuracy and coverage. Finally, two case studies are described, which investigate two biological processes in more detail, that of translation initiation and invasion of the host cell. AVAILABILITY: Predictions produced are available at http://www.bioinformatics.leeds.ac.uk/∼bio5pmrt/PAGODA.

MOTIVATION: A number of methods have been reported that predict protein-protein interactions (PPIs) with high accuracy using only simple sequence-based features such as amino acid 3mer content. This is surprising, given that many protein interactions have high specificity that depends on detailed atomic recognition between physiochemically complementary surfaces. Are the reported high accuracies realistic? RESULTS: We find that the reported accuracies of the predictions are significantly over-estimated, and strongly dependent on the structure of the training and testing datasets used. The choice of which protein pairs are deemed as non-interactions in the training data has a variable impact on the accuracy estimates, and the accuracies can be artificially inflated by a bias towards dominant samples in the positive data which result from the presence of hub proteins in the protein interaction network. To address this bias, we propose a positive set-specific method to create a 'balanced' negative set maintaining the degree distribution for each protein, leading to the conclusion that simple sequence-based features contain insufficient information to be useful for predicting PPIs, but that protein domain-based features have some predictive value. AVAILABILITY: Our method, named 'BRS-nonint', is available at http://www.bioinformatics.leeds.ac.uk/BRS-nonint/. All the datasets used in this study are derived from publicly available data, and are available at http://www.bioinformatics.leeds.ac.uk/BRS-nonint/PPI_RandomBalance.html CONTACT: [email protected]; [email protected].

MOTIVATION: To predict which of the vast number of human single nucleotide polymorphisms (SNPs) are deleterious to gene function or likely to be disease associated is an important problem, and many methods have been reported in the literature. All methods require data sets of mutations classified as 'deleterious' or 'neutral' for training and/or validation. While different workers have used different data sets there has been no study of which is best. Here, the three most commonly used data sets are analysed. We examine their contents and relate this to classifiers, with the aims of revealing the strengths and pitfalls of each data set, and recommending a best approach for future studies. RESULTS: The data sets examined are shown to be substantially different in content, particularly with regard to amino acid substitutions, reflecting the different ways in which they are derived. This leads to differences in classifiers and reveals some serious pitfalls of some data sets, making them less than ideal for non-synonymous SNP prediction. AVAILABILITY: Software is available on request from the authors.

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BACKGROUND: A number of methods that use both protein structural and evolutionary information are available to predict the functional consequences of missense mutations. However, many of these methods break down if either one of the two types of data are missing. Furthermore, there is a lack of rigorous assessment of how important the different factors are to prediction. RESULTS: Here we use Bayesian networks to predict whether or not a missense mutation will affect the function of the protein. Bayesian networks provide a concise representation for inferring models from data, and are known to generalise well to new data. More importantly, they can handle the noisy, incomplete and uncertain nature of biological data. Our Bayesian network achieved comparable performance with previous machine learning methods. The predictive performance of learned model structures was no better than a naïve Bayes classifier. However, analysis of the posterior distribution of model structures allows biologically meaningful interpretation of relationships between the input variables. CONCLUSION: The ability of the Bayesian network to make predictions when only structural or evolutionary data was observed allowed us to conclude that structural information is a significantly better predictor of the functional consequences of a missense mutation than evolutionary information, for the dataset used. Analysis of the posterior distribution of model structures revealed that the top three strongest connections with the class node all involved structural nodes. With this in mind, we derived a simplified Bayesian network that used just these three structural descriptors, with comparable performance to that of an all node network.

Tracking sports players over a large playing area is a challenging problem. The players move quickly, and have large variations in their silhouettes. This paper presents a framework for multi-object tracking, using a CONDENSATION based approach. Each player being tracked is independently fitted to a model, and the sampling probability for the group of samples is calculated as a function of the fitness score of each player. This function rewards consistently good scores, but punishes a group of some very good and some very bad fitness scores. Ground plane information is used throughout, and the predictive stage of the algorithm is improved to incorporate estimates of position from Kalman filters. This helps group the estimated positions of each player, and to aid in tracking through occlusions.