Abstract
Nuclear receptors (NRs) form a family of ligand-activated transcription factors that regulate a wide variety of biological processes, such as homeostasis, reproduction, development, and metabolism. Human genome contains 48 genes encoding NRs. These receptors have become one of the most important targets for therapeutic drug development. According to their different action mechanisms or functions, NRs have been classified into seven subfamilies. With the avalanche of protein sequences generated in the postgenomic age, we are facing the following challenging problems. Given an uncharacterized protein sequence, how can we identify whether it is a nuclear receptor? If it is, what subfamily it belongs to? To address these problems, we developed a predictor called iNR-PhysChem in which the protein samples were expressed by a novel mode of pseudo amino acid composition (PseAAC) whose components were derived from a physical-chemical matrix via a series of auto-covariance and cross-covariance transformations. It was observed that the overall success rate achieved by iNR-PhysChem was over 98% in identifying NRs or non-NRs, and over 92% in identifying NRs among the following seven subfamilies: NR1thyroid hormone like, NR2HNF4-like, NR3estrogen like, NR4nerve growth factor IB-like, NR5fushi tarazu-F1 like, NR6germ cell nuclear factor like, and NR0knirps like. These rates were derived by the jackknife tests on a stringent benchmark dataset in which none of protein sequences included has pairwise sequence identity to any other in a same subset. As a user-friendly web-server, iNR-PhysChem is freely accessible to the public at either http://www.jci-bioinfo.cn/iNR-PhysChem or http://icpr.jci.edu.cn/bioinfo/iNR-PhysChem. Also a step-by-step guide is provided on how to use the web-server to get the desired results without the need to follow the complicated mathematics involved in developing the predictor. It is anticipated that iNR-PhysChem may become a useful high throughput tool for both basic research and drug design.
Highlights
Found within cells, nuclear receptors (NRs) are a class of proteins responsible for sensing steroid and thyroid hormones and certain other molecules
A unique property of NRs that distinguishes themselves from other classes of receptors is their ability to directly interact with and control the expression of genomic DNA, and they are classified as transcription factors [1,2]
Of the ten PC properties, the values for the first six can be directly obtained from the website http://www.csbio.sjtu.edu.cn/ bioinf/PseAAC/PseAAReadme.htm, a part of the web-server PseAAC established for computing pseudo amino acid compositions of proteins according to their sequences [63]
Summary
Nuclear receptors (NRs) are a class of proteins responsible for sensing steroid and thyroid hormones and certain other molecules. In 2009, Gao et al [14] reconstructed the benchmark dataset for NRs and introduced the pseudo amino acid composition (PseAAC) [15] to represent the protein samples in hope to improve the prediction quality.
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