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The "curse of dimensionality" brings new challenges to the feature selection (FS) problem, especially in bioinformatics filed. In this paper, we propose a hybrid Two-Stage Teaching-Learning-Based Optimization (TS-TLBO) algorithm to improve the performance of bioinformatics data classification. In the selection reduction stage, potentially informative features, as well as noisy features, are selected to effectively reduce the search space. In the following comparative self-learning stage, the teacher and the worst student with self-learning evolve together based on the duality of the FS problems to enhance the exploitation capabilities. In addition, an opposition-based learning strategy is utilized to generate initial solutions to rapidly improve the quality of the solutions. We further develop a self-adaptive mutation mechanism to improve the search performance by dynamically adjusting the mutation rate according to the teacher's convergence ability. Moreover, we integrate a differential evolutionary method with TLBO to boost the exploration ability of our algorithm. We conduct comparative experiments on 31 public data sets with different data dimensions, including 7 bioinformatics datasets, and evaluate our TS-TLBO algorithm compared with 11 related methods. The experimental results show that the TS-TLBO algorithm obtains a good feature subset with better classification performance, and indicates its generality to the FS problems.

The rapid development of gene ontology (GO) and huge amount of biomedical data annotated by GO terms necessitate computation of semantic similarity of GO terms and, in turn, measurement of functional similarity of genes based on their annotations. In this paper we propose a novel and efficient method to measure the semantic similarity of GO terms. The proposed method addresses the limitations in existing GO term similarity measurement techniques; it computes the semantic content of a GO term by considering the information content of all of its ancestor terms in the graph. The aggregate information content (AIC) of all ancestor terms of a GO term implicitly reflects the GO term's location in the GO graph and also represents how human beings use this GO term and all its ancestor terms to annotate genes. We show that semantic similarity of GO terms obtained by our method closely matches the human perception. Extensive experimental studies show that this novel method also outperforms all existing methods in terms of the correlation with gene expression data. We have developed web services for measuring semantic similarity of GO terms and functional similarity of genes using the proposed AIC method and other popular methods. These web services are available at http://bioinformatics.clemson.edu/G-SESAME.

RNA interference via exogenous small interference RNAs (siRNA) is a powerful tool in gene function study and disease treatment. Designing efficient and specific siRNA on target gene remains the key issue in RNAi. Although various in silico models have been proposed for rational siRNA design, most of them focus on the efficiencies of selected siRNAs, while limited effort has been made to improve their specificities targeted on specific mRNAs, which is related to reducing off-target effects (OTEs) in RNAi. In our study, we propose for the first time that the enhancement of target specificity of siRNA design can be achieved computationally by domain transfer in heterogeneous data sources from different siRNA targets. A transfer learning based method i.e., heterogeneous regression (HEGS) is presented for target-specific siRNA efficacy modeling and feature selection. Based on the model, (1) the target regression model can be built by extracting information from related data in other targets/experiments, thus increasing the target specificity in siRNA design with the help of information from siRNAs binding to other homologous genes, and (2) the potential features correlated to the current siRNA design can be identified even when there is lack of experimental validated siRNA affinity data on this target. In summary, our findings present useful instructions for a better target-specific siRNA design, with potential applications in genome-wide high-throughput screening of effective siRNA, and will provide further insights on the mechanism of RNAi.

Motivation: Although controlled biochemical or biological vocabularies, such as Gene Ontology (GO) (http://www.geneontology.org), address the need for consistent descriptions of genes in different data sources, there is still no effective method to determine the functional similarities of genes based on gene annotation information from heterogeneous data sources., Results: To address this critical need, we proposed a novel method to encode a GO term's semantics (biological meanings) into a numeric value by aggregating the semantic contributions of their ancestor terms (including this specific term) in the GO graph and, in turn, designed an algorithm to measure the semantic similarity of GO terms. Based on the semantic similarities of GO terms used for gene annotation, we designed a new algorithm to measure the functional similarity of genes. The results of using our algorithm to measure the functional similarities of genes in pathways retrieved from the saccharomyces genome database (SGD), and the outcomes of clustering these genes based on the similarity values obtained by our algorithm are shown to be consistent with human perspectives. Furthermore, we developed a set of online tools for gene similarity measurement and knowledge discovery., Availability: The online tools are available at: http://bioinformatics.clemson.edu/G-SESAME., Supplementary Information: http://bioinformatics.clemson.edu/Publication/Supplement/gsp.htm.