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Nucleic Acids ResNucleic Acids ResearchNucleic Acids Research0305-10481362-4962Oxford University Press 10.1093/nar/gkl37916845014ArticleA compilation of molecular biology web servers: 2006 update on the Bioinformatics Links Directory Fox Joanne A. McMillan Scott Ouellette B. F. Francis *UBC Bioinformatics Centre, University of British Columbia, Michael Smith Laboratories2185 East Mall, Vancouver, BC, Canada V6T 1Z4*To whom correspondence should be addressed. Tel: +1 604 822 3648; Fax:+1 604 608 4795; Email: francis@bioinformatics.ubc.ca01 7 2006 01 7 2006 14 7 2006 34 Web Server issue W3 W5 29 4 2006 02 5 2006 © 2006 The Author(s)2006This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License () which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

The Bioinformatics Links Directory is a public online resource that lists the servers published in this and all previously published Nucleic Acids Research Web Server issues together with other useful tools, databases and resources for bioinformatics and molecular biology research. This rich directory of tools and websites can be browsed and searched with all listed links freely accessible to the public. The 2006 update includes the 149 websites highlighted in the July 2006 issue of Nucleic Acids Research and brings the total number of servers listed in the Bioinformatics Links Directory to over 1000 links. To aid navigation through this growing resource, all link entries contain a brief synopsis, a citation list and are classified by function in descriptive biological categories. The most up-to-date version of this actively maintained listing of bioinformatics resources is available at the Bioinformatics Links Directory website, . A complete list of all links listed in this Nucleic Acids Research 2006 Web Server issue can be accessed online at . The 2006 update of the Bioinformatics Links Directory, which includes the Web Server list and summaries, is also available online at the Nucleic Acids Research website, .
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COMMENTARY
In this era of information and technology, modern scientists must take advantage of cutting-edge data analysis software packages, search the most up-to-date versions of biological databases and use the very latest research resources. As a first step, many researchers head to their favorite search engine on the internet to search for their service of choice only to become lost in a myriad of irrelevant links. For example, if you search for ‘bioinformatics servers’ using Google, you will face the daunting task of sorting through almost a million different websites. In an effort to provide clarity, Nucleic Acids Research has devoted several special issues to compiling molecular biology Web Servers (1) and Databases (2) helping researchers to quickly locate peer-reviewed tools and resources that directly apply to the changing bioinformatics landscape. Over the past 4 years, the NAR Web Server special issue has published a rich collection of over 500 different internet-based resources. This year, the 2006 Web Server issue highlights 149 bioinformatics and molecular biology servers that are all openly available to the world-wide research community. A complete listing of servers from the 2006 Web Server issue can be accessed online at  and in Supplementary Table 1. Together with the long standing Database issue (2), these special issues at Nucleic Acids Research represent a valuable directory of resources for the global life sciences research community.

The Bioinformatics Links Directory, , is a public resource that lists the servers published in this and previous issues of Nucleic Acids Research Web Server issues together with other useful tools, databases and resources for bioinformatics and molecular biology research (1). This directory contains entries of individually curated web resources and links actively collected by researchers at the UBC Bioinformatics Centre from their experiences conducting bioinformatics research, navigating the Internet and teaching bioinformatics. In 2005, Nucleic Acids Research partnered with the Bioinformatics Links Directory to ensure that all of the links from the Web Server special issues were listed. In the Bioinformatics Links Directory, each resource is highlighted by providing a brief summary for each link, functionally classifying links in descriptive functional categories, listing relevant PubMed citations and identifying links as servers from the Nucleic Acids Research Web Server issue. This compilation of web-based research tools currently contains links to over 1000 different servers and databases hosted in over 35 different countries. To aid navigation through this growing resource, links are grouped by biological subject areas (DNA, Protein, RNA, Other Molecules, Expression, Sequence Comparison, Model Organisms, Human Genome, Education, Literature and Computer Related) and are functionally classified into descriptive subcategories. Table 1 shows the number of web servers contained within each subcategory of the Bioinformatics Links Directory. Users can browse the biological categories or can search the Bioinformatics Links Directory directly with a keyword search.

The Bioinformatics Links Directory is a curated resource that is constantly being verified and updated. All links are automatically checked weekly to ensure that no broken links are presented. To help notify users of updates, syndication feeds are provided by a computer-readable file that summarizes any new information published on the Bioinformatics Links Directory website. The Bioinformatics Links Directory feeds use the popular RSS 1.0 (RDF Site Summary) format. By subscribing to the Bioinformatics Links Directory RSS feeds, you can automatically be notified of recent updates and new links added to any topic areas. To learn more about RSS feeds and how to use them on the UBC Bioinformatics website, please look at . The 2006 update of the Bioinformatics Links Directory can also be accessed online via the Web Server summaries link at the Nucleic Acids Research website, .

The scope of the research expertise presented in the 2006 Web Server special issue covers very large number of research applications. Servers from the 2006 NAR Web Server special issue are distributed into 58 of the 86 different functional subcategories contained within the Bioinformatics Links Directory. Figure 1 shows the trend of the number of servers published in the NAR Web Server issues (starting with the first Web Server issue in 2003) for five selected subject areas in the Bioinformatics Links Directory that represent some of the key subcategories in the directory. In 2006, we see an increase in the number of servers for the prediction and design of functional RNAs such as small-interfering RNAs (siRNA) and micro RNAs (miRNAs) target prediction (3). On the other hand, the number of servers for PCR-based primer design, classified under ‘DNA:Tools for the Bench’ has remained relatively steady. In addition to describing new tools, the NAR Web Server issue also contains publications describing updates and new developments for well established gold standards such as the Basic Local Alignment Search Tool (BLAST) (4). Another research area, which has seen a recent increase in the number of web servers, is the prediction and comparison of three-dimensional protein structural features. The ‘Protein: 3-D Structural Features’ subcategory of the Bioinformatics Links Directory lists a total of 53 different servers (18 from the 2006 Web Server issue). These servers offer a rich set of resources for investigating biomolecular structures, and as an example, can carry out tasks such as evaluating the structural features of potential binding regions in proteins (5).

The Bioinformatics Links Directory is an actively maintained community driven resource. Future developments to the Bioinformatics Links Directory include the implementation of advanced search options that will allow users to include the text from PubMed abstracts when searching for relevant links. We are also investigating the development of an ontology and/or meta-tags to aid in the functional classification of servers listed in this Bioinformatics Links Directory as well as others, as was recently suggested by Cannata and colleagues (6). We look forward to working with the community on this exciting development. Suggestions for additions, revisions or corrections to the Bioinformatics Links Directory are strongly encouraged. Please use the Suggest URL link found at , or email your suggestions directly to info@bioinformatics.ubc.ca.

Supplementary Material
[Web Server Summaries]
 The authors would like to acknowledge the efforts of Nucleic Acids Research and the researchers and developers worldwide who invest considerable efforts ensuring that their research is freely accessible and in the public domain. The authors would like to thank Nima Farenzeh and Misbah Naseer for logistical support and assistance in tracking the 2006 Web Server compilation list. The Bioinformatics Links Directory is a community resource built on this commitment to the spirit of open access. The authors would like to recognize all contributors listed on the Acknowledgements page of the Bioinformatics Links Directory, , for their valuable input and suggestions for improvements to the Bioinformatics Links Directory. The Open Access publication charge for this paper has been waived by Oxford University Press in recognition of the work on behalf of the journal.

Conflict of interest statement. None declared.

Figures and Tables
Figure 1 Number of NAR Web Servers from selected subcategories of the Bioinformatic s Links Directory. Over the past 4 years, Nucleic Acids Research has published a special issue every July of useful molecular biology and bioinformatics servers. The Bioinformatics Links Directory () contains a compilation of all of these web servers categorized by subject area. Shown here are the numbers of NAR web servers published from 2003–2006 for five selected subcategories of the Bioinformatics Links Directory: Protein: 3D Structural Features; Expression: Gene Regulation; DNA: Tools for the Bench; Sequence Comparison: Analysis of Aligned Sequences and RNA: Functional RNAs.

Table 1 Summary of the number of web servers listed in each subcategory of the Bioinformatics Links Directory

Name	URLa	
Computer Related	
    Bio-* programming tools	20	
    C/C++	3	
    Databases	2	
    Java	4	
    Linux/Unix	12	
    PERL	5	
    PHP	3	
    Statistics	9	
    Web development	6	
    Web services	6	
DNA	
    Annotations	38	
    Gene prediction	32	
    Mapping and assembly	14	
    Phylogeny reconstruction	37	
    Sequence feature detection	118	
    Sequence polymorphisms	32	
    Sequence retrieval and submission	26	
    Tools for the bench	55	
    Utilities	19	
Education	
    Bioinformatics related news sources	9	
    Community	19	
    Courses, programs and workshops	5	
    Directories and portals	15	
    General	15	
    Tutorials and directed learning resources	9	
Expression	
    cDNA, EST, SAGE	29	
    Gene regulation	96	
    Microarrays	75	
    Protein expression	8	
    Splicing	16	
Human genome	
    Annotations	31	
    Ethics	7	
    Genomics	4	
    Health and disease	14	
    Other resources	25	
    Sequence polymorphisms	25	
Literature	
    Goldmines	6	
    Open access resources	2	
    Search tools	10	
    Text mining	11	
Model organisms	
    Fish	11	
    Fly	16	
    General resources	23	
    Microbes	31	
    Mouse and rat	32	
    Other organisms	18	
    Other vertebrates	10	
    Plants	16	
    Worm	9	
    Yeast	15	
Other molecules	
    Carbohydrates	6	
    Small molecules	3	
Protein	
    2D Structure prediction	51	
    3D Structural features	53	
    3D Structure comparison	35	
    3D Structure prediction	48	
    3D Structure retrieval, viewing	45	
    Biochemical features	37	
    Do-it-all tools for protein	8	
    Domains and motifs	86	
    Function	35	
    Interactions, pathways, enzymes	66	
    Localization and targeting	30	
    Molecular dynamics and docking	19	
    Phylogeny reconstruction	36	
    Presentation and format	13	
    Protein expression	8	
    Proteomics	25	
    Sequence data	7	
    Sequence features	25	
    Sequence retrieval	27	
RNA	
    Functional RNAs	14	
    General Resources	10	
    Motifs	19	
    Sequence retrieval	11	
    Structure prediction, visualization and design	38	
Sequence comparison	
    Alignment editing and visualization	20	
    Analysis of aligned sequences	43	
    Comparative genomics	26	
    Multiple sequence alignments	38	
    Other alignment tools	11	
    Pairwise sequence alignments	22	
    Similarity searching	31	
aA complete listing of all URLs listed in the Nucleic Acids Research 2006 Web Server Issue can be accessed online at .
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REFERENCES
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