For a large research institution and a broad research discipline such as the life sciences, it is a highly important and very challenging task to capture each researcher's expertise, and to match researchers by expertise to assist in identifying inter-disciplinary collaboration opportunities and in making informed policy decisions. The challenges are multi-dimensional, stemming from the needs to (a) provide thorough coverage of the breadth and depth of the disciplinary areas, (b) develop accurate representation of researcher's expertise, and (c) process large volumes of data efficiently. Medical Subject Headings (MeSH), a comprehensive taxonomy for the life sciences, has been widely used for indexing MEDLINE publications. In this paper, we present a novel framework for capturing and matching research expertise based on knowledge encoded in MeSH. Specifically, (1) we design a novel and effective hybrid MeSH classification algorithm by combining state-of-the-art methods, and (2) using MeSH terms aggregated from a researcher's publications, we design a researcher matching algorithm based on semantic similarity that takes into consideration the structure of the MeSH taxonomy.

BACKGROUND: The over consumption of fossil fuels has led to growing concerns over climate change and global warming. Increasing research activities have been carried out towards alternative viable biofuel sources. Of several different biofuel platforms, cyanobacteria possess great potential, for their ability to accumulate biomass tens of times faster than traditional oilseed crops. The cyanobacterium Cyanothece sp. ATCC 51142 has recently attracted lots of research interest as a model organism for such research. Cyanothece can perform efficiently both photosynthesis and nitrogen fixation within the same cell, and has been recently shown to produce biohydrogen--a byproduct of nitrogen fixation--at very high rates of several folds higher than previously described hydrogen-producing photosynthetic microbes. Since the key enzyme for nitrogen fixation is very sensitive to oxygen produced by photosynthesis, Cyanothece employs a sophisticated temporal separation scheme, where nitrogen fixation occurs at night and photosynthesis at day. At the core of this temporal separation scheme is a robust clocking mechanism, which so far has not been thoroughly studied. Understanding how this circadian clock interacts with and harmonizes global transcription of key cellular processes is one of the keys to realize the inherent potential of this organism. RESULTS: In this paper, we employ several state of the art bioinformatics techniques for studying the core circadian clock in Cyanothece sp. ATCC 51142, and its interactions with other key cellular processes. We employ comparative genomics techniques to map the circadian clock genes and genetic interactions from another cyanobacterial species, namely Synechococcus elongatus PCC 7942, of which the circadian clock has been much more thoroughly investigated. Using time series gene expression data for Cyanothece, we employ gene regulatory network reconstruction techniques to learn this network de novo, and compare the reconstructed network against the interactions currently reported in the literature. Next, we build a computational model of the interactions between the core clock and other cellular processes, and show how this model can predict the behaviour of the system under changing environmental conditions. The constructed models significantly advance our understanding of the Cyanothece circadian clock functional mechanisms.

Learning optimal Bayesian networks (BN) from data is NP-hard in general. Nevertheless, certain BN classes with additional topological constraints, such as the dynamic BN (DBN) models, widely applied in specific fields such as systems biology, can be efficiently learned in polynomial time. Such algorithms have been developed for the Bayesian-Dirichlet (BD), Minimum Description Length (MDL), and Mutual Information Test (MIT) scoring metrics. The BD-based algorithm admits a large polynomial bound, hence it is impractical for even modestly sized networks. The MDL-and MIT-based algorithms admit much smaller bounds, but require a very restrictive assumption that all variables have the same cardinality, thus significantly limiting their applicability. In this paper, we first propose an improvement to the MDL-and MIT-based algorithms, dropping the equicardinality constraint, thus significantly enhancing their generality. We also explore local Markov blanket based algorithms for constructing BN in the context of DBN, and show an interesting result: under the faithfulness assumption, the mutual information test based local Markov blanket algorithms yield the same network as learned by the global optimization MIT-based algorithm. Experimental validation on small and large scale genetic networks demonstrates the effectiveness of our proposed approaches.

BACKGROUND: Dynamic Bayesian network (DBN) is among the mainstream approaches for modeling various biological networks, including the gene regulatory network (GRN). Most current methods for learning DBN employ either local search such as hill-climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing, which are only able to locate sub-optimal solutions. Further, current DBN applications have essentially been limited to small sized networks. RESULTS: To overcome the above difficulties, we introduce here a deterministic global optimization based DBN approach for reverse engineering genetic networks from time course gene expression data. For such DBN models that consist only of inter time slice arcs, we show that there exists a polynomial time algorithm for learning the globally optimal network structure. The proposed approach, named GlobalMIT+, employs the recently proposed information theoretic scoring metric named mutual information test (MIT). GlobalMIT+ is able to learn high-order time delayed genetic interactions, which are common to most biological systems. Evaluation of the approach using both synthetic and real data sets, including a 733 cyanobacterial gene expression data set, shows significantly improved performance over other techniques. CONCLUSIONS: Our studies demonstrate that deterministic global optimization approaches can infer large scale genetic networks.

MOTIVATION: Dynamic Bayesian networks (DBN) are widely applied in modeling various biological networks including the gene regulatory network (GRN). Due to the NP-hard nature of learning static Bayesian network structure, most methods for learning DBN also employ either local search such as hill climbing, or a meta stochastic global optimization framework such as genetic algorithm or simulated annealing. RESULTS: This article presents GlobalMIT, a toolbox for learning the globally optimal DBN structure from gene expression data. We propose using a recently introduced information theoretic-based scoring metric named mutual information test (MIT). With MIT, the task of learning the globally optimal DBN is efficiently achieved in polynomial time. AVAILABILITY: The toolbox, implemented in Matlab and C++, is available at http://code.google.com/p/globalmit. CONTACT: [email protected]; [email protected] SUPPLEMENTARY INFORMATION: Supplementary data is available at Bioinformatics online.

Most of gene regulatory network (GRN) studies are based on crisp and parametric algorithms, despite inherent fuzzy nature of gene co-regulation. This paper presents adaptive fuzzy evolutionary GRN Reconstruction (AFEGRN) framework for modeling GRNs. The AFEGRN automatically determines model parameters, such as, number of clusters for fuzzy c-means using fuzzy-PBM index and estimation of Gaussian distribution algorithm. The proposed strategy was tested for breast cancer and normal GRNs. The results conformed to biological knowledge and showed that most of cancer related GRN changes were caused by differentially expressed genes. This demonstrates effectiveness of AFEGRN to model any GRN.

Correct classification and prediction of tumor cells is essential for successful diagnosis and reliable future treatment. However, it is very challenging to distinguish between tumor classes using microarray with thousands of gene expressions. Removing irrelevant genes is very helpful for us to learn the relationship between genes and tumors. In this paper we have used two methods: multivariate permutation test (MPT) and significant analysis of microarray (SAM) to select significant genes for feature selection. Using those selected features, we applied support vector machine, (SVM) with polynomial, radial and linear kernels, to predict the class of testing data. Our result shows that all the samples are classified correctly. We have achieved 100% accuracy in classification among all the samples with polynomial kernel of SVM while Liner kernel shows no misclassification among BRCA1-BRCA2 and BRCA1-sporadic.