Abstract

BackgroundThe nucleus, a highly organized organelle, plays important role in cellular homeostasis. The nuclear proteins are crucial for chromosomal maintenance/segregation, gene expression, RNA processing/export, and many other processes. Several methods have been developed for predicting the nuclear proteins in the past. The aim of the present study is to develop a new method for predicting nuclear proteins with higher accuracy.ResultsAll modules were trained and tested on a non-redundant dataset and evaluated using five-fold cross-validation technique. Firstly, Support Vector Machines (SVM) based modules have been developed using amino acid and dipeptide compositions and achieved a Mathews correlation coefficient (MCC) of 0.59 and 0.61 respectively. Secondly, we have developed SVM modules using split amino acid compositions (SAAC) and achieved the maximum MCC of 0.66. Thirdly, a hidden Markov model (HMM) based module/profile was developed for searching exclusively nuclear and non-nuclear domains in a protein. Finally, a hybrid module was developed by combining SVM module and HMM profile and achieved a MCC of 0.87 with an accuracy of 94.61%. This method performs better than the existing methods when evaluated on blind/independent datasets. Our method estimated 31.51%, 21.89%, 26.31%, 25.72% and 24.95% of the proteins as nuclear proteins in Saccharomyces cerevisiae, Caenorhabditis elegans, Drosophila melanogaster, mouse and human proteomes respectively. Based on the above modules, we have developed a web server NpPred for predicting nuclear proteins .ConclusionThis study describes a highly accurate method for predicting nuclear proteins. SVM module has been developed for the first time using SAAC for predicting nuclear proteins, where amino acid composition of N-terminus and the remaining protein were computed separately. In addition, our study is a first documentation where exclusively nuclear and non-nuclear domains have been identified and used for predicting nuclear proteins. The performance of the method improved further by combining both approaches together.

Highlights

  • The nucleus, a highly organized organelle, plays important role in cellular homeostasis

  • When the protein sequences were splitted into four parts of equal length, with split amino acid compositions (SAAC) we found a Mathews correlation coefficient (MCC) of 0.63 which was similar to that obtained after dividing the proteins into two or three parts of equal length

  • In case a protein contains no domains Support Vector Machines (SVM) module was used for prediction

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Summary

Introduction

The nucleus, a highly organized organelle, plays important role in cellular homeostasis. Several methods have been developed for predicting the nuclear proteins in the past. The aim of the present study is to develop a new method for predicting nuclear proteins with higher accuracy. The genome of the large number of organisms has been completely sequenced or in the final stage of completion due to the advancement in the technology. The functional annotation of proteomes is one of the major challenges in the post genomic era as the numbers of protein with known sequences are growing at exponential rate. Similarity search is one of the most commonly-used techniques for assigning the function of a newly sequenced protein. It fails if query/new protein does not have sequence similarity with a protein whose function is known

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