RefNetBuilder: a platform for construction of integrated reference gene regulatory networks from expressed sequence tags

Ying Li,Edward J Perkins,Nan Wang,Ping Gong,Chaoyang Zhang

doi:10.1186/1471-2105-12-s10-s20

Abstract

BackgroundGene Regulatory Networks (GRNs) provide integrated views of gene interactions that control biological processes. Many public databases contain biological interactions extracted from experimentally validated literature reports, but most furnish only information for a few genetic model organisms. In order to provide a bioinformatic tool for researchers who work with non-model organisms, we developed RefNetBuilder, a new platform that allows construction of putative reference pathways or GRNs from expressed sequence tags (ESTs).ResultsRefNetBuilder was designed to have the flexibility to extract and archive pathway or GRN information from public databases such as the Kyoto Encyclopedia of Genes and Genomes (KEGG). It features sequence alignment tools such as BLAST to allow mapping ESTs to pathways and GRNs in model organisms. A scoring algorithm was incorporated to rank and select the best match for each query EST. We validated RefNetBuilder using DNA sequences of Caenorhabditis elegans, a model organism having manually curated KEGG pathways. Using the earthworm Eisenia fetida as an example, we demonstrated the functionalities and features of RefNetBuilder.ConclusionsThe RefNetBuilder provides a standalone application for building reference GRNs for non-model organisms on a number of operating system platforms with standard desktop computer hardware. As a new bioinformatic tool aimed for constructing putative GRNs for non-model organisms that have only ESTs available, RefNetBuilder is especially useful to explore pathway- or network-related information in these organisms.

Highlights

Gene Regulatory Networks (GRNs) provide integrated views of gene interactions that control biological processes
We first tested the accuracy of RefNetBuilder by reassigning KEGG Orthology (KO) identifiers to the Caenorhabditis elegans genes queried against seven other model species curated in the Kyoto Encyclopedia of Genes and Genomes (KEGG) GENES database
After processing through RefNetBuilder, 9,187 of these expressed sequence tags (ESTs) were assigned to 3,134 unique KO identifier number (KOID) that were mapped to 267 pathways out of the entire 317 KEGG pathways

Summary

Introduction

Gene Regulatory Networks (GRNs) provide integrated views of gene interactions that control biological processes. BioNetBuilder [10,11] and NetMatch [12] are Cytoscape [13] plug-ins for retrieving, integrating, visualization and analysis of known biological networks These programs cannot be applied to species that have no or limited genetic interaction information. Other tools such as BlastPath [14] and OmicViZ [15], Cytoscape plug-ins, allow network mapping across species based on sequence homology They only map a query species to its closely related model organisms; and have limitations in the number of query genes / proteins. To the best of our knowledge, no tools are currently available that provide an integrated environment for building GRNs for less-studied non-model organisms from incomplete genomic or EST sequencing data This motivates us to develop Reference Network Builder or RefNetBuilder, a cyber-based platform that constructs homologous reference GRNs, to fill this gap

Methods

Results

Conclusion