Topological and organizational properties of the products of house-keeping and tissue-specific genes in protein-protein interaction networks

Wen-Hsien Lin,Wei-Chung Liu,Ming-Jing Hwang

doi:10.1186/1752-0509-3-32

Abstract

BackgroundHuman cells of various tissue types differ greatly in morphology despite having the same set of genetic information. Some genes are expressed in all cell types to perform house-keeping functions, while some are selectively expressed to perform tissue-specific functions. In this study, we wished to elucidate how proteins encoded by human house-keeping genes and tissue-specific genes are organized in human protein-protein interaction networks. We constructed protein-protein interaction networks for different tissue types using two gene expression datasets and one protein-protein interaction database. We then calculated three network indices of topological importance, the degree, closeness, and betweenness centralities, to measure the network position of proteins encoded by house-keeping and tissue-specific genes, and quantified their local connectivity structure.ResultsCompared to a random selection of proteins, house-keeping gene-encoded proteins tended to have a greater number of directly interacting neighbors and occupy network positions in several shortest paths of interaction between protein pairs, whereas tissue-specific gene-encoded proteins did not. In addition, house-keeping gene-encoded proteins tended to connect with other house-keeping gene-encoded proteins in all tissue types, whereas tissue-specific gene-encoded proteins also tended to connect with other tissue-specific gene-encoded proteins, but only in approximately half of the tissue types examined.ConclusionOur analysis showed that house-keeping gene-encoded proteins tend to occupy important network positions, while those encoded by tissue-specific genes do not. The biological implications of our findings were discussed and we proposed a hypothesis regarding how cells organize their protein tools in protein-protein interaction networks. Our results led us to speculate that house-keeping gene-encoded proteins might form a core in human protein-protein interaction networks, while clusters of tissue-specific gene-encoded proteins are attached to the core at more peripheral positions of the networks.

Highlights

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information
We mapped the genes expressed to the Human Protein Reference Database (HPRD) [27] and identified the corresponding proteins in order to construct a tissue-specific protein-protein interaction (PPI) network
The proportion of total number of nodes in the largest network fragment varied from 0.901 to 0.975 among different PPI networks for the HuGE Index dataset and from 0.831 to 0.970 for the Expressed Sequence Tag (EST)-Serial Analysis of Gene Expression (SAGE) dataset; the extent of connectivity of every PPI network constructed in this study is high

Summary

Introduction

Human cells of various tissue types differ greatly in morphology despite having the same set of genetic information. In the post-genomic era, the step in modern molecular biology is to understand how gene products, or proteins, interact to perform cellular functions [2]. Using microarray-based [6] and tag-based [7,8] techniques, gene expression patterns in different tissue types can be quantified, and the identification of house-keeping and tissue-specific genes is possible with modern statistical analysis [4,9]. Little is known about how the protein products of house-keeping and tissue-specific genes are organized or embedded within the protein-protein interaction (PPI) networks that give rise to the observed similarities and differences in morphology between cells.

Methods

Results

Discussion

Conclusion