Dataset Information

Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks.

ABSTRACT: Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN approach by predicting in vitro activities and in vivo functions in the proline racemase superfamily (PRS; InterPro IPR008794). The predictions were verified by measuring in vitro activities for 51 proteins in 12 families in the PRS that represent ?85% of the sequences; in vitro activities of pathway enzymes, carbon/nitrogen source phenotypes, and/or transcriptomic studies confirmed the predicted pathways. The synergistic use of sequence similarity networks3 and GNNs will facilitate the discovery of the components of novel, uncharacterized metabolic pathways in sequenced genomes.

SUBMITTER: Zhao S

PROVIDER: S-EPMC4113996 | biostudies-literature | 2014 Jun

REPOSITORIES: biostudies-literature

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Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks.

Zhao Suwen S Sakai Ayano A Zhang Xinshuai X Vetting Matthew W MW Kumar Ritesh R Hillerich Brandan B San Francisco Brian B Solbiati Jose J Steves Adam A Brown Shoshana S Akiva Eyal E Barber Alan A Seidel Ronald D RD Babbitt Patricia C PC Almo Steven C SC Gerlt John A JA Jacobson Matthew P MP

eLife 20140630

Metabolic pathways in eubacteria and archaea often are encoded by operons and/or gene clusters (genome neighborhoods) that provide important clues for assignment of both enzyme functions and metabolic pathways. We describe a bioinformatic approach (genome neighborhood network; GNN) that enables large scale prediction of the in vitro enzymatic activities and in vivo physiological functions (metabolic pathways) of uncharacterized enzymes in protein families. We demonstrate the utility of the GNN a ...[more]

PMID: 24980702

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Project description:BackgroundStudies have shown that miRNAs are functionally associated with the development of many human diseases, but the roles of miRNAs in diseases and their underlying molecular mechanisms have not been fully understood. The research on miRNA-disease interaction has received more and more attention. Compared with the complexity and high cost of biological experiments, computational methods can rapidly and efficiently predict the potential miRNA-disease interaction and can be used as a beneficial supplement to experimental methods.ResultsIn this paper, we proposed a novel computational model of kernel neighborhood similarity and multi-network bidirectional propagation (KNMBP) for miRNA-disease interaction prediction, especially for new miRNAs and new diseases. First, we integrated multiple data sources of diseases and miRNAs, respectively, to construct a novel disease semantic similarity network and miRNA functional similarity network. Secondly, based on the modified miRNA-disease interactions, we use the kernel neighborhood similarity algorithm to calculate the disease kernel neighborhood similarity and the miRNA kernel neighborhood similarity. Finally, we utilize bidirectional propagation algorithm to predict the miRNA-disease interaction scores based on the integrated disease similarity network and miRNA similarity network. As a result, the AUC value of 5-fold cross validation for all interactions by KNMBP is 0.93126 based on the commonly used dataset, and the AUC values for all interactions, for all miRNAs, for all disease is 0.93795、0.86363、0.86937 based on another dataset extracted by ourselves, which are higher than other state-of-the-art methods. In addition, our model has good parameter robustness. The case study further demonstrated the predictive performance of the model for novel miRNA-disease interactions.ConclusionsOur KNMBP algorithm efficiently integrates multiple omics data from miRNAs and diseases to stably and efficiently predict potential miRNA-disease interactions. It is anticipated that KNMBP would be a useful tool in biomedical research.

Dataset Information

Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks.

Publications

Prediction and characterization of enzymatic activities guided by sequence similarity and genome neighborhood networks.

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