Abstract
BackgroundUnderstanding the constituent domains of oncogenes, their origins and their fusions may shed new light about the initiation and the development of cancers.ResultsWe have developed a computational pipeline for identification of functional domains of human genes, prediction of the origins of these domains and their major fusion events during evolution through integration of existing and new tools of our own. An application of the pipeline to 124 well-characterized human oncogenes has led to the identification of a collection of domains and domain pairs that occur substantially more frequently in oncogenes than in human genes on average. Most of these enriched domains and domain pairs are related to tyrosine kinase activities. In addition, our analyses indicate that a substantial portion of the domain-fusion events of oncogenes took place in metazoans during evolution.ConclusionWe expect that the computational pipeline for domain identification, domain origin and domain fusion prediction will prove to be useful for studying other groups of genes.
Highlights
Understanding the constituent domains of oncogenes, their origins and their fusions may shed new light about the initiation and the development of cancers
Using the computational procedures outlined in Material and Methods, we have carried out a detailed analysis of oncogene domains and co-occurring domains for their origins and functional analysis
In order to further analyze the statistical difference between the domain origin distribution of oncogenes versus that of the other genes, we have compared our results with Lipika et al [15], which presented an analysis on the origins of the conserved domains in the whole human proteome
Summary
Understanding the constituent domains of oncogenes, their origins and their fusions may shed new light about the initiation and the development of cancers. An oncogene is a modified gene that promotes unregulated proliferation of cells, increasing the chance that a normal cell develops into a tumor cell, possibly resulting in cancer [1]. Numerous oncogenes have been identified and classified into different groups based on their cellular functions. Protein domains are compact and semi-independent units of a protein, each of which may consist of one or more contiguous segments of a peptide chain and have its own biological function [3]. They are generally viewed as the basic unit of protein function and evolution. Various sequence- and structure-based methods have been developed for the identification of protein domains [4,5,6], and several domain databases, such as DALI [7], PFAM [8], SMART [9] and Prodom [10], have been established
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