Published online 15 September 2009 Nucleic Acids Research, 2010, Vol. 38, Database issue D633–D639 doi:10.1093/nar/gkp760 The Gene Wiki: community intelligence applied to human gene annotation Jon W. Huss III1, Pierre Lindenbaum2, Michael Martone3, Donabel Roberts4, Angel Pizarro5, Faramarz Valafar4, John B. Hogenesch5 and Andrew I. Su1,* 1Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121, USA, 2Department of Bioinformatics, CEPH/Fondation Jean-Dausset, Paris, France, 3Rush University Medical College, Chicago, IL 60612, 4San Diego State University, Bioinformatics and Medical Informatics Graduate Program, San Diego, CA 92182 and 5Department of Pharmacology, Institute for Translational Medicine and Therapeutics, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA Received August 14, 2009; Revised August 26, 2009; Accepted August 29, 2009 ABSTRACT illustrated by two simple analyses of links between PubMed and the Entrez Gene database. Annotating the function of all human genes is a The first analysis showed that while there are several critical, yet formidable, challenge. Current gene well-studied genes that have thousands of indexed annotation efforts focus on centralized curation citations in the literature, that degree of functional anno- resources, but it is increasingly clear that this tation falls off steeply (1). Almost 80% of Entrez Gene approach does not scale with the rapid growth of entries had five or fewer linked references in PubMed; the biomedical literature. The Gene Wiki utilizes an almost 50% had zero linked references (Figure 1A). alternative and complementary model based on the This pattern was even more pronounced when examining principle of community intelligence. Directly integra- links to the Gene Ontology (also shown in Figure 1A). ted within the online encyclopedia, Wikipedia, the Clearly, there remains much work to be done to func- goal of this effort is to build a gene-specific review tionally annotate the human genome and to com- prehensively catalog these findings in gene annotation article for every gene in the human genome, where databases. each article is collaboratively written, continuously A second analysis examined the rate at which PubMed updated and community reviewed. Previously, entries were being linked to Entrez Gene (Figure 1B). we described the creation of Gene Wiki ‘stubs’ Between 1970 and 2008, the number of publications for approximately 9000 human genes. Here, we added to PubMed grew at an annualized rate of 3.4%. describe ongoing systematic improvements to On examining that same time period, it was found that the these articles to increase their utility. Moreover, number of articles that are currently linked to at least one we retrospectively examine the community usage Entrez Gene entry ‘grew’ by 18% per year, but still <4% and improvement of the Gene Wiki, providing of all PubMed entries in recent years (and <1.5% overall) evidence of a critical mass of users and editors. are linked to Entrez Gene. Assuming that >4% of Gene Wiki articles are freely accessible within the PubMed-indexed articles have relevance to human gene function, this finding suggests that the rate limiting step Wikipedia web site, and additional links and infor- is not generating the data, but capturing the derived mation are available at http://en.wikipedia knowledge in gene annotation databases. .org/wiki/Portal:Gene_Wiki. Currently, the process of annotating gene function typ- ically entails large-scale efforts by the model organism community (2–4) and genome annotation centers (5). INTRODUCTION Formal annotation of gene function often utilizes con- The sequencing and analysis of the human genome have trolled vocabularies like Gene Ontology (6). While the largely elucidated the ‘parts list’ of the cellular machinery annotation process can be aided by the use of in the form of approximately 25 000 genes. However, computational tools, ultimately the assignment of gene the comprehensive annotation of gene function remains function is a manual process requiring the attention of a formidable challenge. The scale of the task ahead is one or more domain experts (7). This centralized model *To whom correspondence should be addressed. Tel: 858-812-1500; Fax: 858-812-1570; Email: [email protected] ß The Author(s) 2009. Published by Oxford University Press. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/ by-nc/2.5/uk/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. D634 Nucleic Acids Research, 2010, Vol. 38, Database issue A 10000 TP53 TNF PubMed links APOE GO Annotaons MTHFR 1000 HLA-DRB1 31672 genes (78%) have five or fewer IL6 ACE linked PubMed references TGFB1 100 EGFR Counts VEGFA 19709 genes (49%) have zero linked 10 PubMed references 40234 entries in Entrez Gene 1 0 10000 20000 30000 40000 Genes, sorted by decreasing counts B Figure 1. Analysis of links between the Entrez Gene and PubMed databases. (A) Examining the degree of gene annotation from the perspective of Entrez Gene, we found that while a few genes are very well annotated with links to PubMed references, the vast majority of genes have few or no linked references. (B) Examining links from the perspective of PubMed, we found that only a small fraction of published articles are linked to human genes. Taken together, these findings suggest that the traditional model of centralized curation is not scaling well with the rate of scientific research, and that complementary approaches based on community intelligence may be worth exploring. has been very successful in its goal to systematically involved in the annotation effort to scale up to the rate of advance gene annotation, creating essential tools and data generation’ (8). ontologies in the process. Thus, although leaders in the curation community have However, this model alone may not be sufficient to effi- successfully set up a robust pipeline and infrastructure, ciently and systematically annotate gene function. Many and although the individuals in the curation community leading voices in the gene annotation and model are clearly skilled in the annotation process, the amount of organism communities recently wrote a feature article in resources devoted to this important task may be simply Nature describing the current state and future of insufficient relative to the volume of biomedical data being biocuration (8). They noted the immense challenge to the generated. curator community (typically numbering in tens to Recently, several efforts have been published, which hundreds of people) to keep pace with the biomedical lit- attempt to harness the principle of ‘community intelli- erature (currently 18 million articles in PubMed, roughly gence’ (9–15). In particular, we introduced the Gene 750 000 new articles per year). Specifically, these curation Wiki (11), an effort to systematically annotate articles in experts suggest that merely preserving the existing the online encyclopedia, Wikipedia, for approximately models of gene annotation will lead to an increasing lag 9000 human genes. Articles were created or amended between curated data and biological knowledge, and that with content mined from structured gene annotation ‘sooner or later, the research community will need to be databases, including Entrez Gene, Ensembl, UniProt and Nucleic Acids Research, 2010, Vol. 38, Database issue D635 the Protein Data Bank (PDB). Although the emphasis of the Wikimedia Commons. To aid in browsing and the Gene Wiki is on describing human gene function, data searching, PDB images were also categorized according from model organisms is often contributed as appropriate. to their assignments in the Structural Classification of Here, we present an update describing the recent sys- Proteins (SCOP) database (19). The set of PDB structures tematic improvements to the Gene Wiki. Moreover, we can be browsed at http://commons.wikimedia.org/wiki report on a retrospective analysis of Gene Wiki usage /SCOP. and editing. Finally, we offer some concluding remarks The easy availability of thumbnail images for almost all on general progress and challenges facing efforts to PDB structures will encourage their incorporation into collaboratively engage the entire community of scientists. relevant Gene Wiki and Wikipedia articles. To begin this process, we added an image gallery of PDB thumbnails to every Gene Wiki page with solved structures. To maintain DATABASE CONTENT balance with the rest of the pages’ content, the image As described earlier (11), the initial Gene Wiki effort galleries were shown in an expandable window at the focused on creating or amending gene pages to include a bottom of each Gene Wiki page. In total, PDB image free-text summary, an ‘infobox’ with links to public galleries were added to 2852 Gene Wiki pages with databases, Gene Ontology annotations and when avail- a total of 16 018 links to PDB structures. For example, able, protein structure identifiers. These data were primar- the PDB gallery for MDM2 (http://en.wikipedia ily harvested from the Entrez Gene database (16). Since .org/wiki/Mdm2) shows PDB structures corresponding that publication, we have introduced several other system- to the unbound protein, as well as structures in complex atic improvements to the Gene Wiki. with its p53 peptide ligand and two small molecule inhibitors. Protein interactions On-demand web service Our previously