Dataset Information

Predicting residue-residue contacts and helix-helix interactions in transmembrane proteins using an integrative feature-based random forest approach.

ABSTRACT: Integral membrane proteins constitute 25-30% of genomes and play crucial roles in many biological processes. However, less than 1% of membrane protein structures are in the Protein Data Bank. In this context, it is important to develop reliable computational methods for predicting the structures of membrane proteins. Here, we present the first application of random forest (RF) for residue-residue contact prediction in transmembrane proteins, which we term as TMhhcp. Rigorous cross-validation tests indicate that the built RF models provide a more favorable prediction performance compared with two state-of-the-art methods, i.e., TMHcon and MEMPACK. Using a strict leave-one-protein-out jackknifing procedure, they were capable of reaching the top L/5 prediction accuracies of 49.5% and 48.8% for two different residue contact definitions, respectively. The predicted residue contacts were further employed to predict interacting helical pairs and achieved the Matthew's correlation coefficients of 0.430 and 0.424, according to two different residue contact definitions, respectively. To facilitate the academic community, the TMhhcp server has been made freely accessible at http://protein.cau.edu.cn/tmhhcp.

SUBMITTER: Wang XF

PROVIDER: S-EPMC3203928 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Predicting residue-residue contacts and helix-helix interactions in transmembrane proteins using an integrative feature-based random forest approach.

Wang Xiao-Feng XF Chen Zhen Z Wang Chuan C Yan Ren-Xiang RX Zhang Ziding Z Song Jiangning J

PloS one 20111028 10

Integral membrane proteins constitute 25-30% of genomes and play crucial roles in many biological processes. However, less than 1% of membrane protein structures are in the Protein Data Bank. In this context, it is important to develop reliable computational methods for predicting the structures of membrane proteins. Here, we present the first application of random forest (RF) for residue-residue contact prediction in transmembrane proteins, which we term as TMhhcp. Rigorous cross-validation tes ...[more]

PMID: 22046350

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Project description:BackgroundThe ability to predict which pairs of amino acid residues in a protein are in contact with each other offers many advantages for various areas of research that focus on proteins. For example, contact prediction can be used to reduce the computational complexity of predicting the structure of proteins and even to help identify functionally important regions of proteins. These predictions are becoming especially important given the relatively low number of experimentally determined protein structures compared to the amount of available protein sequence data.ResultsHere we have developed and benchmarked a set of machine learning methods for performing residue-residue contact prediction, including random forests, direct-coupling analysis, support vector machines, and deep networks (stacked denoising autoencoders). These methods are able to predict contacting residue pairs given only the amino acid sequence of a protein. According to our own evaluations performed at a resolution of +/- two residues, the predictors we trained with the random forest algorithm were our top performing methods with average top 10 prediction accuracy scores of 85.13% (short range), 74.49% (medium range), and 54.49% (long range). Our ensemble models (stacked denoising autoencoders combined with support vector machines) were our best performing deep network predictors and achieved top 10 prediction accuracy scores of 75.51% (short range), 60.26% (medium range), and 43.85% (long range) using the same evaluation. These tests were blindly performed on targets from the CASP11 dataset; and the results suggested that our models achieved comparable performance to contact predictors developed by groups that participated in CASP11.ConclusionsDue to the challenging nature of contact prediction, it is beneficial to develop and benchmark a variety of different prediction methods. Our work has produced useful tools with a simple interface that can provide contact predictions to users without requiring a lengthy installation process. In addition to this, we have released our C++ implementation of the direct-coupling analysis method as a standalone software package. Both this tool and our RFcon web server are freely available to the public at http://dna.cs.miami.edu/RFcon /.

Project description:The study of protein-protein interactions (PPIs) can be very important for the understanding of biological cellular functions. However, detecting PPIs in the laboratories are both time-consuming and expensive. For this reason, there has been much recent effort to develop techniques for computational prediction of PPIs as this can complement laboratory procedures and provide an inexpensive way of predicting the most likely set of interactions at the entire proteome scale. Although much progress has already been achieved in this direction, the problem is still far from being solved. More effective approaches are still required to overcome the limitations of the current ones. In this study, a novel Multi-scale Local Descriptor (MLD) feature representation scheme is proposed to extract features from a protein sequence. This scheme can capture multi-scale local information by varying the length of protein-sequence segments. Based on the MLD, an ensemble learning method, the Random Forest (RF) method, is used as classifier. The MLD feature representation scheme facilitates the mining of interaction information from multi-scale continuous amino acid segments, making it easier to capture multiple overlapping continuous binding patterns within a protein sequence. When the proposed method is tested with the PPI data of Saccharomyces cerevisiae, it achieves a prediction accuracy of 94.72% with 94.34% sensitivity at the precision of 98.91%. Extensive experiments are performed to compare our method with existing sequence-based method. Experimental results show that the performance of our predictor is better than several other state-of-the-art predictors also with the H. pylori dataset. The reason why such good results are achieved can largely be credited to the learning capabilities of the RF model and the novel MLD feature representation scheme. The experiment results show that the proposed approach can be very promising for predicting PPIs and can be a useful tool for future proteomic studies.

Dataset Information

Predicting residue-residue contacts and helix-helix interactions in transmembrane proteins using an integrative feature-based random forest approach.

Publications

Predicting residue-residue contacts and helix-helix interactions in transmembrane proteins using an integrative feature-based random forest approach.

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