Gene functional similarity search tool (GFSST)

Peisen Zhang,Jinghui Zhang,James J Russo,Huitao Sheng,Brian Osborne,Kenneth Buetow

doi:10.1186/1471-2105-7-135

Abstract

BackgroundWith the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood. Increasing amounts of data about genes, gene products and their functions have been stored in databases. To facilitate selection of candidate genes for gene-disease research, genetic association studies, biomarker and drug target selection, and animal models of human diseases, it is essential to have search engines that can retrieve genes by their functions from proteome databases. In recent years, the development of Gene Ontology (GO) has established structured, controlled vocabularies describing gene functions, which makes it possible to develop novel tools to search genes by functional similarity.ResultsBy using a statistical model to measure the functional similarity of genes based on the Gene Ontology directed acyclic graph, we developed a novel Gene Functional Similarity Search Tool (GFSST) to identify genes with related functions from annotated proteome databases. This search engine lets users design their search targets by gene functions.ConclusionAn implementation of GFSST which works on the UniProt (Universal Protein Resource) for the human and mouse proteomes is available at GFSST Web Server. GFSST provides functions not only for similar gene retrieval but also for gene search by one or more GO terms. This represents a powerful new approach for selecting similar genes and gene products from proteome databases according to their functions.

Highlights

With the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood
Using different similarity measures and search methodologies, we have developed a search engine: Gene Functional Similarity Search Tool (GFSST), to identify candidate genes based on their functional similarities
We have developed a GFSST search engine for human and mouse proteomes

Summary

Introduction

With the completion of the genome sequences of human, mouse, and other species and the advent of high throughput functional genomic research technologies such as biomicroarray chips, more and more genes and their products have been discovered and their functions have begun to be understood. The tumor suppressor gene BRCA1 suppresses cell growth and participates in transcription-coupled DNA damage repair. Mutations in BRCA1 increase the risk of early onset breast cancer as well as ovarian and prostate cancer [[1,2], and [3]]. Genes with functions similar to BRCA1 can be considered additional candidate genetic risk factors for breast, ovarian, prostate, or other cancers. One common approach to identify functionally similar genes is to find genes that share significant sequence homology. Functional similarity does not always require sequence similarity Both P53 [4] and BRCA1 [5] function as tumor suppressor genes. Similar to BRCA1, mutations in P53 have been found in breast cancer patients [6]. A sequence similarity search tool, such as BLAST [7], is unable to reveal their functional similarity

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