Motivation: Binary datasets represent a compact and simple way to store data about the relationships between a group of objects and their possible properties. In the last few years, different biclustering algorithms have been specially developed to be applied to binary datasets. Several approaches based on matrix factorization, suffix trees or divide-and-conquer techniques have been proposed to extract useful biclusters from binary data, and these approaches provide information about the distribution of patterns and intrinsic correlations. Results: A novel approach to extracting biclusters from binary datasets, BiBit, is introduced here. The results obtained from different experiments with synthetic data reveal the excellent performance and the robustness of BiBit to density and size of input data. Also, BiBit is applied to a central nervous system embryonic tumor gene expression dataset to test the quality of the results. A novel gene expression preprocessing methodology, based on expression level layers, and the selective search performed by BiBit, based on a very fast bit-pattern processing technique, provide very satisfactory results in quality and computational cost. The power of biclustering in finding genes involved simultaneously in different cancer processes is also shown. Finally, a comparison with Bimax, one of the most cited binary biclustering algorithms, shows that BiBit is faster while providing essentially the same results. Availability: The source and binary codes, the datasets used in the experiments and the results can be found at: http://www.upo.es/eps/bigs/BiBit.html Contact:dsrodbae@upo.es Supplementary information: Supplementary data are available at Bioinformatics online.

Establishing an association between variables is always of interest in genomic studies. Generation of DNA microarray gene expression data introduces a variety of data analysis issues not encountered in traditional molecular biology or medicine. Frequent pattern mining (FPM) has been applied successfully in business and scientific data for discovering interesting association patterns, and is becoming a promising strategy in microarray gene expression analysis. We review the most relevant FPM strategies, as well as surrounding main issues when devising efficient and practical methods for gene association analysis (GAA). We observed that, so far, scalability achieved by efficient methods does not imply biological soundness of the discovered association patterns, and vice versa. Ideally, GAA should employ a balanced mining model taking into account best practices employed by methods reviewed in this survey. Integrative approaches, in which biological knowledge plays an important role within the mining process, are becoming more reliable.

Gene networks have arisen as a promising tool in the comprehensive modeling and analysis of complex diseases. Particularly in viral infections, the understanding of the host-pathogen mechanisms, and the immune response to these, is considered a major goal for the rational design of appropriate therapies. For this reason, the use of gene networks may well encourage therapy-associated research in the context of the coronavirus pandemic, orchestrating experimental scrutiny and reducing costs. In this work, gene co-expression networks were reconstructed from RNA-Seq expression data with the aim of analyzing the time-resolved effects of gene Ly6E in the immune response against the coronavirus responsible for murine hepatitis (MHV). Through the integration of differential expression analyses and reconstructed networks exploration, significant differences in the immune response to virus were observed in Ly6E ${}^{\Delta HSC}$ compared to wild type animals. Results show that Ly6E ablation at hematopoietic stem cells (HSCs) leads to a progressive impaired immune response in both liver and spleen. Specifically, depletion of the normal leukocyte mediated immunity and chemokine signaling is observed in the liver of Ly6E ${}^{\Delta HSC}$ mice. On the other hand, the immune response in the spleen, which seemed to be mediated by an intense chromatin activity in the normal situation, is replaced by ECM remodeling in Ly6E ${}^{\Delta HSC}$ mice. These findings, which require further experimental characterization, could be extrapolated to other coronaviruses and motivate the efforts towards novel antiviral approaches.

In the last few years, gene networks have become one of most important tools to model biological processes. Among other utilities, these networks visually show biological relationships between genes. However, due to the large amount of the currently generated genetic data, their size has grown to the point of being unmanageable. To solve this problem, it is possible to use computational approaches, such as heuristics-based methods, to analyze and optimize gene network’s structure by pruning irrelevant relationships. In this paper we present a new method, called GeSOp, to optimize large gene network structures. The method is able to perform a considerably prune of the irrelevant relationships comprising the input network. To do so, the method is based on a greedy heuristic to obtain the most relevant subnetwork. The performance of our method was tested by means of two experiments on gene networks obtained from different organisms. The first experiment shows how GeSOp is able not only to carry out a significant reduction in the size of the network, but also to maintain the biological information ratio. In the second experiment, the ability to improve the biological indicators of the network is checked. Hence, the results presented show that GeSOp is a reliable method to optimize and improve the structure of large gene networks.

Gene networks have become a powerful tool in the comprehensive analysis of gene expression. Due to the increasing amount of available data, computational methods for networks generation must deal with the so-called curse of dimensionality in the quest for the reliability of the obtained results. In this context, ensemble strategies have significantly improved the precision of results by combining different measures or methods. On the other hand, structure optimization techniques are also important in the reduction of the size of the networks, not only improving their topology but also keeping a positive prediction ratio. In this work, we present Ensemble and Greedy networks (EnGNet), a novel two-step method for gene networks inference. First, EnGNet uses an ensemble strategy for co-expression networks generation. Second, a greedy algorithm optimizes both the size and the topological features of the network. Not only do achieved results show that this method is able to obtain reliable networks, but also that it significantly improves topological features. Moreover, the usefulness of the method is proven by an application to a human dataset on post-traumatic stress disorder, revealing an innate immunity-mediated response to this pathology. These results are indicative of the method’s potential in the field of biomarkers discovery and characterization.