Dataset Information

Incorporating evolutionary information and functional domains for identifying RNA splicing factors in humans.

ABSTRACT: Regulation of pre-mRNA splicing is achieved through the interaction of RNA sequence elements and a variety of RNA-splicing related proteins (splicing factors). The splicing machinery in humans is not yet fully elucidated, partly because splicing factors in humans have not been exhaustively identified. Furthermore, experimental methods for splicing factor identification are time-consuming and lab-intensive. Although many computational methods have been proposed for the identification of RNA-binding proteins, there exists no development that focuses on the identification of RNA-splicing related proteins so far. Therefore, we are motivated to design a method that focuses on the identification of human splicing factors using experimentally verified splicing factors. The investigation of amino acid composition reveals that there are remarkable differences between splicing factors and non-splicing proteins. A support vector machine (SVM) is utilized to construct a predictive model, and the five-fold cross-validation evaluation indicates that the SVM model trained with amino acid composition could provide a promising accuracy (80.22%). Another basic feature, amino acid dipeptide composition, is also examined to yield a similar predictive performance to amino acid composition. In addition, this work presents that the incorporation of evolutionary information and domain information could improve the predictive performance. The constructed models have been demonstrated to effectively classify (73.65% accuracy) an independent data set of human splicing factors. The result of independent testing indicates that in silico identification could be a feasible means of conducting preliminary analyses of splicing factors and significantly reducing the number of potential targets that require further in vivo or in vitro confirmation.

SUBMITTER: Hsu JB

PROVIDER: S-EPMC3217973 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Incorporating evolutionary information and functional domains for identifying RNA splicing factors in humans.

Hsu Justin Bo-Kai JB Bretaña Neil Arvin NA Lee Tzong-Yi TY Huang Hsien-Da HD

PloS one 20111116 11

Regulation of pre-mRNA splicing is achieved through the interaction of RNA sequence elements and a variety of RNA-splicing related proteins (splicing factors). The splicing machinery in humans is not yet fully elucidated, partly because splicing factors in humans have not been exhaustively identified. Furthermore, experimental methods for splicing factor identification are time-consuming and lab-intensive. Although many computational methods have been proposed for the identification of RNA-bindi ...[more]

PMID: 22110674

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Project description:Antifreeze proteins are important antifreeze materials that have been widely used in industry, including in cryopreservation, de-icing, and food storage applications. However, the quantity of some commercially produced antifreeze proteins is insufficient for large-scale industrial applications. Further, many antifreeze proteins have properties such as cytotoxicity, severely hindering their applications. Understanding the mechanisms underlying the protein-ice interactions and identifying novel antifreeze proteins are, therefore, urgently needed. In this study, to uncover the mechanisms underlying protein-ice interactions and provide an efficient and accurate tool for identifying antifreeze proteins, we assessed various evolutionary features based on position-specific scoring matrices (PSSMs) and evaluated their importance for discriminating of antifreeze and non-antifreeze proteins. We then parsimoniously selected seven key features with the highest importance. We found that the selected features showed opposite tendencies (regarding the conservation of certain amino acids) between antifreeze and non-antifreeze proteins. Five out of the seven features had relatively high contributions to the discrimination of antifreeze and non-antifreeze proteins, as revealed by a principal component analysis, i.e., the conservation of the replacement of Cys, Trp, and Gly in antifreeze proteins by Ala, Met, and Ala, respectively, in the related proteins, and the conservation of the replacement of Arg in non-antifreeze proteins by Ser and Arg in the related proteins. Based on the seven parsimoniously selected key features, we established a classifier using support vector machine, which outperformed the state-of-the-art tools. These results suggest that understanding evolutionary information is crucial to designing accurate automated methods for discriminating antifreeze and non-antifreeze proteins. Our classifier, therefore, is an efficient tool for annotating new proteins with antifreeze functions based on sequence information and can facilitate their application in industry.

Dataset Information

Incorporating evolutionary information and functional domains for identifying RNA splicing factors in humans.

Publications

Incorporating evolutionary information and functional domains for identifying RNA splicing factors in humans.

Similar Datasets

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