Most functional magnetic resonance imaging studies rely on estimates of hierarchically organized functional brain networks whose segregation and integration reflect the cognitive and behavioral changes in humans. However, most existing methods for estimating the community structure of networks from both individual and group-level analysis methods do not account for the variability between subjects. In this paper, we develop a new multilayer community detection method based on Bayesian latent block model (LBM). The method can robustly detect the community structure of weighted functional networks with an unknown number of communities at both individual and group levels and retain the variability of the individual networks. For validation, we propose a new community structure-based multivariate Gaussian generative model to simulate synthetic signal. Our simulation study shows that the community memberships estimated by hierarchical Bayesian inference are consistent with the predefined node labels in the generative model. The method is also tested via split-half reproducibility using working memory task fMRI data of 100 unrelated healthy subjects from the Human Connectome Project. Analyses using both synthetic and real data show that our proposed method is more accurate and reliable compared with the commonly used (multilayer) modularity models. The code of this work is available at: https://github.com/LingbinBian/CommuDetectLBM.

BACKGROUND: Many problems in bioinformatics involve classification based on features such as sequence, structure or morphology. Given multiple classifiers, two crucial questions arise: how does their performance compare, and how can they best be combined to produce a better classifier? A classifier can be evaluated in terms of sensitivity and specificity using benchmark, or gold standard, data, that is, data for which the true classification is known. However, a gold standard is not always available. Here we demonstrate that a Bayesian model for comparing medical diagnostics without a gold standard can be successfully applied in the bioinformatics domain, to genomic scale data sets. We present a new implementation, which unlike previous implementations is applicable to any number of classifiers. We apply this model, for the first time, to the problem of finding the globally optimal logical combination of classifiers. RESULTS: We compared three classifiers of protein subcellular localisation, and evaluated our estimates of sensitivity and specificity against estimates obtained using a gold standard. The method overestimated sensitivity and specificity with only a small discrepancy, and correctly ranked the classifiers. Diagnostic tests for swine flu were then compared on a small data set. Lastly, classifiers for a genome-wide association study of macular degeneration with 541094 SNPs were analysed. In all cases, run times were feasible, and results precise. The optimal logical combination of classifiers was also determined for all three data sets. Code and data are available from http://bioinformatics.monash.edu.au/downloads/. CONCLUSIONS: The examples demonstrate the methods are suitable for both small and large data sets, applicable to the wide range of bioinformatics classification problems, and robust to dependence between classifiers. In all three test cases, the globally optimal logical combination of the classifiers was found to be their union, according to three out of four ranking criteria. We propose as a general rule of thumb that the union of classifiers will be close to optimal.

MOTIVATION: The analysis of multiple sequence alignments is allowing researchers to glean valuable insights into evolution, as well as identify genomic regions that may be functional, or discover novel classes of functional elements. Understanding the distribution of conservation levels that constitutes the evolutionary landscape is crucial to distinguishing functional regions from non-functional. Recent evidence suggests that a binary classification of evolutionary rates is inappropriate for this purpose and finds only highly conserved functional elements. Given that the distribution of evolutionary rates is multi-modal, determining the number of modes is of paramount concern. Through simulation, we evaluate the performance of a number of information criterion approaches derived from MCMC simulations in determining the dimension of a model. RESULTS: We utilize a deviance information criterion (DIC) approximation that is more robust than the approximations from other information criteria, and show our information criteria approximations do not produce superfluous modes when estimating conservation distributions under a variety of circumstances. We analyse the distribution of conservation for a multiple alignment comprising four primate species and mouse, and repeat this on two additional multiple alignments of similar species. We find evidence of six distinct classes of evolutionary rates that appear to be robust to the species used. AVAILABILITY: Source code and data are available at http://dl.dropbox.com/u/477240/changept.zip.

Due to advancements in computational ability, enhanced technology and a reduction in the price of genotyping, more data are being generated for understanding genetic associations with diseases and disorders. However, with the availability of large data sets comes the inherent challenges of new methods of statistical analysis and modeling. Considering a complex phenotype may be the effect of a combination of multiple loci, various statistical methods have been developed for identifying genetic epistasis effects. Among these methods, logic regression (LR) is an intriguing approach incorporating tree-like structures. Various methods have built on the original LR to improve different aspects of the model. In this study, we review four variations of LR, namely Logic Feature Selection, Monte Carlo Logic Regression, Genetic Programming for Association Studies, and Modified Logic Regression-Gene Expression Programming, and investigate the performance of each method using simulated and real genotype data. We contrast these with another tree-like approach, namely Random Forests, and a Bayesian logistic regression with stochastic search variable selection.

Metaheuristics such as Estimation of Distribution Algorithms and the Cross-Entropy method use probabilistic modelling and inference to generate candidate solutions in optimization problems. The model fitting task in this class of algorithms has largely been carried out to date based on maximum likelihood. An alternative approach that is prevalent in statistics and machine learning is to use Bayesian inference. In this paper, we provide a framework for the application of Bayesian inference techniques in probabilistic model-based optimization. Based on this framework, a simple continuous Bayesian Estimation of Distribution Algorithm is described. We evaluate and compare this algorithm experimentally with its maximum likelihood equivalent, UMDAGc.

MOTIVATION: Despite many successes of conventional DNA sequencing methods, some DNAs remain difficult or impossible to sequence. Unsequenceable regions occur in the genomes of many biologically important organisms, including the human genome. Such regions range in length from tens to millions of bases, and may contain valuable information such as the sequences of important genes. The authors have recently developed a technique that renders a wide range of problematic DNAs amenable to sequencing. The technique is known as sequence analysis via mutagenesis (SAM). This paper presents a number of algorithms for analysing and interpreting data generated by this technique. RESULTS: The essential idea of SAM is to infer the target sequence using the sequences of mutants derived from the target. We describe three algorithms used in this process. The first algorithm predicts the number of mutants that will be required to infer the target sequence with a desired level of accuracy. The second algorithm infers the target sequence itself, using the mutant sequences. The third algorithm assigns quality values to each inferred base. The algorithms are illustrated using mutant sequences generated in the laboratory.

MOTIVATION: A consensus sequence for a family of related sequences is, as the name suggests, a sequence that captures the features common to most members of the family. Consensus sequences are important in various DNA sequencing applications and are a convenient way to characterize a family of molecules. RESULTS: This paper describes a new algorithm for finding a consensus sequence, using the popular optimization method known as simulated annealing. Unlike the conventional approach of finding a consensus sequence by first forming a multiple sequence alignment, this algorithm searches for a sequence that minimises the sum of pairwise distances to each of the input sequences. The resulting consensus sequence can then be used to induce a multiple sequence alignment. The time required by the algorithm scales linearly with the number of input sequences and quadratically with the length of the consensus sequence. We present results demonstrating the high quality of the consensus sequences and alignments produced by the new algorithm. For comparison, we also present similar results obtained using ClustalW. The new algorithm outperforms ClustalW in many cases.