EGenBio: A Data Management System for Evolutionary Genomics and Biodiversity

  • Laila A Nahum1, 2,

    Affiliated with

    • Matthew T Reynolds1,

      Affiliated with

      • Zhengyuan O Wang1,

        Affiliated with

        • Jeremiah J Faith3,

          Affiliated with

          • Rahul Jonna4,

            Affiliated with

            • Zhi J Jiang1,

              Affiliated with

              • Thomas J Meyer1 and

                Affiliated with

                • David D Pollock1, 5Email author

                  Affiliated with

                  BMC Bioinformatics20067(Suppl 2):S7

                  DOI: 10.1186/1471-2105-7-S2-S7

                  Published: 26 September 2006

                  Abstract

                  Background

                  Evolutionary genomics requires management and filtering of large numbers of diverse genomic sequences for accurate analysis and inference on evolutionary processes of genomic and functional change. We developedEvolutionaryGenomics andBiodiversity (EGenBio;http://​egenbio.​lsu.​edu) to begin to address this.

                  Description

                  EGenBiois a system for manipulation and filtering of large numbers of sequences, integrating curated sequence alignments and phylogenetic trees, managing evolutionary analyses, and visualizing their output.EGenBiois organized into three conceptual divisions,Evolution,Genomics, andBiodiversity. TheGenomicsdivision includes tools for selecting pre-aligned sequences from different genes and species, and for modifying and filtering these alignments for further analysis. Species searches are handled through queries that can be modified based on a tree-based navigation system and saved. TheBiodiversitydivision contains tools for analyzing individual sequences or sequence alignments, whereas theEvolutiondivision contains tools involving phylogenetic trees. Alignments are annotated with analytical results and modification history using ourPRAEDformat. A miscellaneousToolssection andHelpframework are also available.EGenBiowas developed around our comparative genomic research and a prototype database of mtDNA genomes. It utilizes MySQL-relational databases and dynamic page generation, and calls numerous custom programs.

                  Conclusion

                  EGenBiowas designed to serve as a platform for tools and resources to ease combined analysis in evolution, genomics, and biodiversity.

                  Background

                  Large-scale genomic technologies have generated an extraordinary amount of data in the past few decades. Consequently, a huge effort has been made toward creating biological databases and systems to organize, analyze, and share information with the world-wide community[14]. The application of genomic technologies to molecular evolution has opened new frontiers in the interdisciplinary field of evolutionary genomics, and this has given rise to a great potential to elucidate complex questions in biology[2, 5]. Understanding of evolutionary processes is critical, since they determine the sequence, structure, and function of macromolecules, and ultimately shape the higher-level biological complexity of organisms.

                  Genomic biodiversity has been defined as dense sampling of molecular data from diverse taxonomic groups for large genomic regions or complete genomes[6], and inferences concerning evolutionary processes are greatly improved by adopting combined molecular and computational approaches that include a large amount of genomic biodiversity[69]. We have found that the study of evolutionary genomics in the context of a dense sampling of species gives rise to many unique data processing problems, and so have developed theEvolutionaryGenomics andBiodiversity (EGenBio) project as a web-based system to simplify large-scale evolutionary data management.

                  The central aim ofEGenBiois to provide integrated analysis and visualization of raw sequence data, alignments, and phylogenetic trees, to rapidly curate and annotate that data, and to filter that data based on these annotations for further analysis of specific genomic contexts. It is designed to be robust to change and easily extensible to other datasets and other analytical programs. To accomplish this,EGenBiohas web-based interfaces designed to: (1) access computational tools for phylogenetic and evolutionary analyses; (2) facilitate the construction of large-scale sequence and alignment datasets across diverse taxa; and (3) provide a framework for comparative analysis of diverse genes and genomes.EGenBiomay also serve to promote the utility of increases in the scale of genomic biodiversity.

                  Overview

                  The three conceptual divisions ofEGenBio(Evolution,Genomics, andBiodiversity) serve to organize web-based access to the primary custom-built tools (Figure1, Table1). TheGenomicsdivision provides access to pre-aligned sequence databases, and serves as a means of flexibly selecting genes and species/genomes of interest and producing a concatenated and annotated alignment for use in further analysis. The data is stored in a MySQL database and accessed "on the fly". Our prototype database contains complete vertebrate mitochondrial genomes that are mostly obtained from NCBI RefSeq annotations[10], but also contains "pre-submission" genomes provided by other investigators. Private access to "pre-submission" genomes allows users to pre-integrate their data with publicly available data for analysis in the primary genome publication, and is available on request. Complex searches can be stored, and registered users can create a personal list of searches that are retained in memory. Alignments for protein-coding genes are based on their amino acid sequences using ClustalW[11], but either amino acid or nucleotide alignments can be selected. TheBiodiversitydivision is a collection of tools for analysis of alignments or sets of sequences (Table1). These tools do not require a phylogenetic tree. Examples include lists of sequences available, database summaries, graphical representation of gene order information, and summary information on selected or uploaded alignments. This section also includes tools to aid experimental analysis of evolutionary genomics predictions, such as generating primers that represent all possible permutations of a set of sequences, or generating degenerate primers that reflect a sample from a posterior probability prediction of a particular ancestral sequence. TheEvolutiondivision includes tools (Table1) that incorporate or extract information from phylogenetic trees and that translate from accession numbers to human-readable labels for sequences (e.g., genus species designations, or common names of organisms). This division also includes access to programs for processing and visualization of alignment filters (described below), coevolutionary analysis[12, 13], and saturation mutagenesis analysis[14].
                  http://static-content.springer.com/image/art%3A10.1186%2F1471-2105-7-S2-S7/MediaObjects/12859_2006_Article_1301_Fig1_HTML.jpg
                  Figure 1

                  Organization of EGenBio.EGenBiois accessed through a splash page that links to the three main divisions,Evolution,Genomics, andBiodiversity(A). Each division has its own access page to the tools that are organized in that division. For example, theGenomicsdivision page is shown in (B). The division of each page is clearly marked to allow quick movement among divisions and to theToolssection and mirroredHelppages.

                  Table 1

                  Custom tools* currently in the main divisions ofEGenBio

                  Division

                  Tool Name

                  Tool Description

                  Genomics

                  SearchSequence

                  Search the mtDNA genome database for DNA or protein sequences

                  Genomics

                  SearchAlignment

                  Search the mtDNA genome database for sequence alignments

                  Genomics

                  SearchHuSequence

                  Search the human mtDNA database for DNA or protein sequences

                  Genomics

                  SearchHuAlignment

                  Search the human mtDNA database for sequence alignments

                  Evolution

                  TranslateTree

                  Translate labels of a tree file

                  Evolution

                  FilterViz

                  Visualize filters associated with alignments

                  Evolution

                  TreeReader

                  Extract tree clusters along with information on branch lengths

                  Evolution

                  SaturationTool

                  Visualize results from saturation mutagenesis MCMC analysis

                  Evolution

                  LnLCorr

                  Detect coevolution among residues using LRTs and trees

                  Biodiversity

                  SpeciesList

                  List species currently inEGenBio

                  Biodiversity

                  SpeciesSearch

                  Search species by taxonomic group or NCBI genome identifier

                  Biodiversity

                  LocusOrder

                  Display mitochondrial gene order for specified taxa

                  Biodiversity

                  DatabaseSummary

                  Provide information about theEGenBiodatabases

                  Biodiversity

                  PrimerPermuter

                  Generate permutations for use in primer design

                  Biodiversity

                  PrimerAlternatives

                  Produce degenerate primers that reflect amino acid variation

                  *All tools listed are original toEGenBio, except that alignments are based on ClustalW [11].

                  In addition to the three main sections,EGenBiocontains aToolssection that serves as a repository for small stand-alone tools that may also exist as components of other pages, or which serve other simple purposes. TheHelplink leads not to a separate section, but rather to what we will call a separate "framework". The structure of theHelpframework mirrors the main framework exactly, but instead of linking to actual tools,Helppages link to detailed descriptions and documentation for each page. Invisible to most users, a hiddenDesignframework allows for rapid editing and movement of page and site structure information from design to laboratory testing stages, and finally to public access.

                  Discussion and Conclusion

                  EGenBiois a web-based system for analysis in evolutionary genomics and biodiversity. It provides tools and resources for quickly creating, modifying, and analyzing large alignment datasets in ways that we have found useful in our own computer-based and experimental evolutionary genomics research. Our prototype database of complete vertebrate mitochondrial genomes represents the densest complete set of genes currently available from closely related organisms. It can be accessed flexibly according to comma-separated queries or a phylogenetic tree navigation system.EGenBiois designed to be easily extensible to use with other protein complexes and other analytical programs. Our goal is to incorporate and utilize as many existing programs as possible, and to develop only "added value" programs. In the current public version, all tools are novel to our system except that alignments are created using ClustalW[11]. ThePRAEDalignment annotation system based on data filters allows alignments to be modified easily according to user interest in annotation features, and allows for the results of analyses to be returned as further annotations on the alignments. Since it is derived from theNEXUSformat, it is easy to add batch commands to direct analyses using many common phylogenetic analysis programs. ThePRAEDformat and data filters are a unique feature of theEGenBiosystem.

                  Future modules under development inEGenBioinclude the creation of additional data filters, incorporation of more genes for analysis of functional divergence, development of further visualization tools for statistical analyses of evolutionary dynamics, and automated procedures for analysis using existing programs and tools. We also welcome feedback from the scientific community on areas of general need for integrated evolutionary genomics tools.EGenBiois publicly available and can be accessed athttp://​egenbio.​lsu.​edu/​ via anonymous login. User accounts that allow users to save search parameters and results are provided upon request. Incorporation and private access to pre-publication data can also be accommodated upon request. Replication of theEGenBiosystem would require a Linux-based operating system capable of running Perl, Perl-GD, R, PHP, MySQL, and an Apache web server. It would also require installation of numerous custom scripts in addition to ClustalW.

                  Abbreviations

                  LRT: 

                  Likelihood ratio test

                  MCMC: 

                  Markov chain Monte Carlo

                  mtDNA: 

                  mitochondrial DNA

                  NCBI: 

                  National Center for Biotechnology Information

                  PRAED

                  PRagmaticAnalysis ofEvolutionaryData.

                  Declarations

                  Acknowledgements

                  This work was partly funded by the National Institutes of Health (R22/R33 Innovation and Development grant to David Pollock), the National Science Foundation (CBM2/EPSCOR), and the State of Louisiana (Biological Computation and Visualization Center, Governor's Biotechnology Initiative, and startup funds to David Pollock). We also anonymously thank other current and former members in the Pollock laboratory for assisting in the development and testing of various tools, and thank Chad Jarreau, Jonathan Bonin, Jonny Roberts Jr., Patricia Ledwig, Stephen McCullough, Sujatha Muralidharan, and Yonatan Platt for contributing to theBiodiversityimage collection.

                  Authors’ Affiliations

                  (1)
                  Department of Biological Sciences, Biological Computation and Visualization Center, Louisiana State University
                  (2)
                  Marine Biological Laboratory, Josephine Bay Paul Center
                  (3)
                  Bioinformatics Program, Boston University
                  (4)
                  Arizona State Department, Division of Developmental Disabilities,  
                  (5)
                  Department of Biochemistry and Molecular Genetics, University of Colorado School of Medicine

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                  Copyright

                  © Nahum et al. 2006

                  This article is published under license to BioMed Central Ltd. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://​creativecommons.​org/​licenses/​by/​2.​0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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