Searching for uses and users in Gene Ontology research



Despite millions of dollars in investment over the past decade in the creation and maintenance of the Gene Ontology (GO), little is known about how (or even if) its intended end users -biomedical researchers - actually employ the ontology and its related databases and interfaces in their work. This project is a preliminary investigation of what evidence exists in the literature of specific uses of GO by researchers, and of use cases proposed for researchers by system designers. This work will help inform future in-depth studies of the specific information needs and research questions that researchers might use GO and other similar knowledge structures to address. It also provides to library and information science researchers and practitioners some insight into the quantity, sources, and breadth of publications about GO that exist.

The Gene Ontology is intended as a means of cross-organism integration of knowledge of the molecular functions, biological processes, and subcellular localization of gene products (Gene Ontology Consortium, 2008a). Much of basic biomedical research is performed on organisms that serve as surrogates for humans, due to their relative biological simplicity and the inappropriateness of direct experimentation on humans. GO integrates knowledge about gene function, process, and location across such so-called “model” organisms as the fruitfly Drosophila melanogaster, the mouse Mus musculus, and budding yeast Saccharomyces cerevisiae.

While dozens of ontologies and other controlled vocabularies for biomedical research, clinical medical informatics, and general science are under development (Smith, et al., 2007), and many different systems and applications have been developed to employ these vocabularies, there is often a knowledge gap between ontology developers, maintainers, and system designers on the one hand, and the target audience of end users (Rubin, Shah & Noy, 2008). Ontology developers and curators in biomedical informatics are frequently subject matter experts, holding the same academic credentials as the putative end users, and often have similar backgrounds and laboratory experience. Although developers may have a user perspective in mind, they are often in the position of trying to promote adoption and use of such systems to practicing researchers (see, e.g., Rhee, Dickerson & Xu, 2006).

Rubin, Shah & Noy (2008) classify biomedical ontology use into six functional types: search and query of heterogeneous biomedical data, data exchange among applications, information integration, natural language processing, representation of encyclopedic knowledge, and computer reasoning with data (76). While abstract examples of uses of ontologies in these areas are discussed, specific cases are not.

To better understand actual use, this exploratory literature-based study investigated the existence of user studies of biomedical scientists' use of the Gene Ontology; experimental articles that cite the use of GO; GO infrastructure and -application articles that describe user needs assessment; and articles that provide GO use cases.


Numbers of GO-related articles were tabulated from searches in several bibliographic databases (PubMed/MEDLINE, EMBASE, BIOSIS, ISI Web of Science, Scopus, the ACM Digital Library, IEEE Xplore, and Library and Information Science Abstracts). Since MEDLINE primarily contains bioscience articles, the other bibliographic databases were searched to ensure user-focused studies from disciplines under-represented in PubMed (such as library and information science, sociology, ethnography, and social studies of science [SSS] / science and technology studies [STS]) were not overlooked. Search strategies for PubMed and the ACM Digital Library were created (Fig. 1) to locate articles related to uses of GO.

Figure 1.

PubMed and ACM Digital Library search strategies for user-focused GO articles

A manual examination of the GO Bibliography (Gene Ontology Consortium, 2008b), a database of GO-related articles maintained on the GO site, was used to supplement the bibliographic database searches. The GO Bibliography categorizes papers into 19 types, including 8 that explicitly refer to types of ‘use’ (Table 1). The full bibliographic records for all citations from each of the eight ‘use’ categories were retrieved from PubMed. These were loaded into a purpose-built MySQL database and the intersection of the eight sets was computed in order to identify articles duplicated across categories. Articles were characterized by publication year, journal name, and author affiliation.

Table 1. GO Bibliography ‘use’ categories and article quantities
Source: (2008-02-26)
Use of GO in gene expression studies857
Use of GO in clinical applications485
Use of GO in biological databases164
Use of GO in proteomics studies125
Use of GO in network modeling and analysis122
Use of GO in comparative genomics and evolutionary analysis109
Use of GO in data or text mining98
Use of GO to support predictions59


Literature characterization

Table 2 presents the article quantities retrieved from the GO Bibliography and searches of the bibliographic databases, using both keyword searches on ‘gene ontology’ and the more focused search strategies from Figure 1. Very few articles were found when queries included terms related to use and users.

Table 2. Quantities of GO-related articles by source, as of 2008-02-26
  • *

    Some articles are classified in multiple categories, so summing category totals yields 3,108.

GO Bibliography (distinct articles across all categories*)1,824
- Distinct articles across all ‘use’ categories1,342
PubMed/MEDLINEgene ontology1,408
-in titlegene ontology[ti]171
-in title & abstractgene ontology[tiab]1,237
-using search strategy #1See Fig. 1145
-using search strategy #2See Fig. 194
ScopusTITLE-ABS-KEY (“gene ontology”)1,556
ISI Web of ScienceTopic = (“gene ontology”) | Title = (“gene ontology”)1,528
EMBASEgene ontology1,308
BIOSISgene ontology1,234
ACM Digital Librarygene ontology (“gene ontology”) & (“use case”)338 5
 (“gene ontology”) & (“use case”)5
IEEE Xploregene ontology119
Library and Information Science Abstracts (LISA)gene ontology3

The total number of articles across all GO Bibliography ‘use’ categories is 2,019, but due to the classification of some articles into multiple categories, and duplicated references in some lists, there are 1,342 distinct articles. Table 3 shows the distribution of distinct use-focused articles by publication year. Year-over-year growth has been significant, more than doubling every year in the early years, and slowing to 26% from 2006 to 2007 (still more than 1 new article per day). Table 4 shows the distribution of distinct use-focused articles by the top 10 (of a total of 404) journals, which account for 56% of the total number of articles, following a classic power law probability distribution. The top ten journals are a mix of biological science journals and bioinformatics and computational biology journals.

Table 3. Articles by publication year
Publication yearArticles
  • *

    As of 2008-02-26

Table 4. Articles by journal (top 10 of 104)
Nucleic Acids Research133
BMC Bioinformatics127
PLoS Genetics93
PLoS Computational Biology64
BMC Genomics61
Physiological Genomics45
PLoS Biology42
Genome Biology41

Details of use cases

Many GO papers assert the usefulness of GO and other ontologies for data integration across organisms, information retrieval, and knowledge discovery, but do not provide more precise needs and uses of end-user researchers. Specific use cases within a small number of the articles were identified and examined.

Sahoo, et al (in press) use an example of the complex problem of integrating information about the genetic components of nicotine dependence to illustrate the need for ontologies in the creation of semantically integrated information resources. They provide three specific research questions a scientist might be interested in if pursuing this topic: “Which genes participate in a large number of pathways? Which genes (or gene products) interact with each other? Which genes are expressed in the brain?” (4) More detail is provided on each of the questions as the features of the system are described.

The “use case development” section in Shegogue & Zheng (2005) describes the use of class, responsibility, and collaboration (CRC) cards to gather requirements information which was then used to create a detailed document describing the main and alternate steps in a model. While it provides details of a biological process of interest, this is not a narrative scenario that describes a biological problem, question, or information need.

The “use cases” presented in Shah, et al. (2005) and Blake and Bult (2006) are examples of possible tasks and queries that a user might perform (e.g., a “known item” search using an accession number for a biological object such as a sequence), but specific motivations for these types of tasks, or the underlying biological significance or user relevance, are not discussed. Shah et al. do describe a use case where their system can be used to compile a list of reagents for use in identifying orthologous human genes that exist in model organisms, which “represent essential genes which are candidates for human disease agents” (11). Blake and Bult note that examination of ontological annotations in databases “can be extremely useful for experimental biologists making crucial decisions as to allocation of research resources for further characterization of specific genes (317)”.



The fact that few of the articles explicitly mention users or use cases indicates that little has been published on the information needs and practices of biomedical researchers. However, since many of the articles were published in biology-focused journals, it is possible that a substantial proportion of the articles could in fact be examples of researchers using GO to address biological problems, or the nature of the biological questions could be implicit in the design of the project being reported. More work is needed to explore the nature of these papers, and to assess the differences in the types of problems and questions explored in the underlying projects.

Future Work

Both bibliographic and human subject research are needed to understand more about the information needs and user motivations for the use of GO. A fuller characterization of the literature identified above should be carried out to categorize types of uses, identify specific use cases, and segment the document sets into articles produced by ontology developers, system developers, and end-users.

The knowledge gained from the bibliographic research can be employed in studies of potential and actual end-user scientists' motivations for using (and not using) GO in their work. Some researchers are relying upon GO annotations to validate computationally-derived predictions of biological activity (e.g., Kaminker, et al, 2007), which suggests that the perceived information quality (Nicolaou & McKnight, 2006) of GO is high. However, as MacMullen (2006) notes, the quality of GO annotations, like their use, is largely unquantified, and may have a variety of facets whose weights vary depending upon specific uses. Future work in this area could include awareness assessments conducted with prospective GO end-users based upon ideas such as the technology acceptance model (TAM) (e.g., Davis, 1989). Established constructs such as perceived ease of use (PEOU) and perceived usefulness (PU), which have been explored in relation to adoption of bioinformatics tools by scientists (see, e.g., Shachak, Shuval & Fine, 2007) could be supplemented with others, such as the perceived advantage of using GO instead of another approach, or the use of one GO interface over another, and perceived goal attainment (PGA) (Glaser & Backer, 1980) - how can the use of GO help a researcher achieve her goals?

As Blake and Bult (2006) and Sahoo, et al. (in press) note, the true power of ontologies for driving industrial-scale e-Science research processes that repurpose the vast amounts of extant data has not yet been realized. User-centered and problem-based research by social scientists that addresses the range of researchers' information problems requires a far deeper and richer understanding of the specific information needs and tasks scientists face in the spectrum of their work, from large data management activities down to the individual experiments that comprise “the long tail of science” (Palmer, et al., 2007) performed in thousands of labs worldwide.