Human gene regulatory networks (GRN) can be difficult to interpret due to a tangle of edges interconnecting thousands of genes. We constructed a general human GRN from extensive transcription factor and microRNA target data obtained from public databases. In a subnetwork of this GRN that is active during estrogen stimulation of MCF-7 breast cancer cells, we benchmarked automated algorithms for identifying core regulatory genes (transcription factors and microRNAs). Among these algorithms, we identified K-core decomposition, pagerank and betweenness centrality algorithms as the most effective for discovering core regulatory genes in the network evaluated based on previously known roles of these genes in MCF-7 biology as well as in their ability to explain the up or down expression status of up to 70% of the remaining genes. Finally, we validated the use of K-core algorithm for organizing the GRN in an easier to interpret layered hierarchy where more influential regulatory genes percolate towards the inner layers. The integrated human gene and miRNA network and software used in this study are provided as supplementary materials (S1 Data) accompanying this manuscript.

BACKGROUND: Dynamic aspects of gene regulatory networks are typically investigated by measuring system variables at multiple time points. Current state-of-the-art computational approaches for reconstructing gene networks directly build on such data, making a strong assumption that the system evolves in a synchronous fashion at fixed points in time. However, nowadays omics data are being generated with increasing time course granularity. Thus, modellers now have the possibility to represent the system as evolving in continuous time and to improve the models' expressiveness. RESULTS: Continuous time Bayesian networks are proposed as a new approach for gene network reconstruction from time course expression data. Their performance was compared to two state-of-the-art methods: dynamic Bayesian networks and Granger causality analysis. On simulated data, the methods comparison was carried out for networks of increasing size, for measurements taken at different time granularity densities and for measurements unevenly spaced over time. Continuous time Bayesian networks outperformed the other methods in terms of the accuracy of regulatory interactions learnt from data for all network sizes. Furthermore, their performance degraded smoothly as the size of the network increased. Continuous time Bayesian networks were significantly better than dynamic Bayesian networks for all time granularities tested and better than Granger causality for dense time series. Both continuous time Bayesian networks and Granger causality performed robustly for unevenly spaced time series, with no significant loss of performance compared to the evenly spaced case, while the same did not hold true for dynamic Bayesian networks. The comparison included the IRMA experimental datasets which confirmed the effectiveness of the proposed method. Continuous time Bayesian networks were then applied to elucidate the regulatory mechanisms controlling murine T helper 17 (Th17) cell differentiation and were found to be effective in discovering well-known regulatory mechanisms, as well as new plausible biological insights. CONCLUSIONS: Continuous time Bayesian networks were effective on networks of both small and large size and were particularly feasible when the measurements were not evenly distributed over time. Reconstruction of the murine Th17 cell differentiation network using continuous time Bayesian networks revealed several autocrine loops, suggesting that Th17 cells may be auto regulating their own differentiation process.

Character recognition in scene images is an extremely challenging task. Although several techniques are reported performing well, they pertain to English only. This paper focuses on Devanagari character recognition from scene images. Devanagari script is very popular language and has very typical characteristics different from other scripts, particularly English. Combination of basic Devanagari consonants and vowels in multi-variegated ways can yield as many as 100s of characters. Building a classifier to recognize all these classes will be a difficult task. To alleviate this problem, a novel part-based model technique is proposed. 40 basic classes were identified from the Devanagari script for the same purpose. The technique was proposed so as to classify an instance of one these classes in any given test sample. Procuring a large dataset for training is not feasible in the case of scene images. To simultaneously solve this problem, we developed our technique that can use either the machine printed or the handwritten dataset for training. We present our results on the publicly available dataset (DSIW2K) containing images of street scenes taken in New Delhi, India.

MOTIVATION: Discovery of nucleotide motifs that are localized with respect to a certain biological landmark is important in several appli-cations, such as in regulatory sequences flanking the transcription start site, in the neighborhood of known transcription factor binding sites, and in transcription factor binding regions discovered by massively parallel sequencing (ChIP-Seq). RESULTS: We report an algorithm called LocalMotif to discover such localized motifs. The algorithm is based on a novel scoring function, called spatial confinement score, which can determine the exact interval of localization of a motif. This score is combined with other existing scoring measures including over-representation and relative entropy to determine the overall prominence of the motif. The approach successfully discovers biologically relevant motifs and their intervals of localization in scenarios where the motifs cannot be discovered by general motif finding tools. It is especially useful for discovering multiple co-localized motifs in a set of regulatory sequences, such as those identified by ChIP-Seq. AVAILABILITY AND IMPLEMENTATION: The LocalMotif software is available at http://www.comp.nus.edu.sg/~bioinfo/LocalMotif.

In silico motif finding algorithms are often used for discovering protein-DNA binding sites in a set of regulatory sequences. Current algorithms mainly address motif discovery in short sequences. Analyzing long sequences can be quite challenging not only due to increasing time and memory requirements of the algorithm, but also decreasing accuracy. However, in case the motif is localized in a short interval of the long sequences relative to an anchor point, it is tenable to detect it easily by restricting the search to that interval. But the region of localization of the motif is not known a priori. This paper reports an algorithm called LocalMotif to detect localized motifs in long regulatory sequences. A novel score function predicts the region of localization of the motif. This score is combined with other scoring measures including Z-score and relative entropy to detect the motif. The algorithm is optimized for fast processing of long regulatory sequences. Tests on simulated and real datasets confirm that LocalMotif accurately determines the region of localization of motifs and automatically discovers the biologically relevant motifs, which can be detected by other motif finding algorithms only when the search is restricted to the relevant interval