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A method for increasing expressivity of Gene Ontology annotations using a compositional approach

Huntley, Rachael P. and Harris, Midori A. and Alam-Faruque, Yasmin and Blake, Judith A. and Carbon, Seth and Dietze, Heiko and Dimmer, Emily C. and Foulger, Rebecca E. and Hill, David P. and Khodiyar, Varsha K. and Lock, Antonia and Lomax, Jane and Lovering, Ruth C. and Mutowo-Meullenet, Prudence and Sawford, Tony and Van Auken, Kimberly and Wood, Valerie and Mungall, Christopher J. (2014) A method for increasing expressivity of Gene Ontology annotations using a compositional approach. BMC Bioinformatics, 15 . Art. No. 155. ISSN 1471-2105. PMCID PMC4039540.

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Background: The Gene Ontology project integrates data about the function of gene products across a diverse range of organisms, allowing the transfer of knowledge from model organisms to humans, and enabling computational analyses for interpretation of high-throughput experimental and clinical data. The core data structure is the annotation, an association between a gene product and a term from one of the three ontologies comprising the GO. Historically, it has not been possible to provide additional information about the context of a GO term, such as the target gene or the location of a molecular function. This has limited the specificity of knowledge that can be expressed by GO annotations. Results: The GO Consortium has introduced annotation extensions that enable manually curated GO annotations to capture additional contextual details. Extensions represent effector–target relationships such as localization dependencies, substrates of protein modifiers and regulation targets of signaling pathways and transcription factors as well as spatial and temporal aspects of processes such as cell or tissue type or developmental stage. We describe the content and structure of annotation extensions, provide examples, and summarize the current usage of annotation extensions. Conclusions: The additional contextual information captured by annotation extensions improves the utility of functional annotation by representing dependencies between annotations to terms in the different ontologies of GO, external ontologies, or an organism’s gene products. These enhanced annotations can also support sophisticated queries and reasoning, and will provide curated, directional links between many gene products to support pathway and network reconstruction.

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Van Auken, Kimberly0000-0002-1706-4196
Additional Information:© 2014 Huntley et al.; licensee BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver ( applies to the data made available in this article, unless otherwise stated. Received: 4 March 2014 Accepted: 15 May 2014. Published: 21 May 2014. We thank Mark McDowall and Kim Rutherford for producing the PomBase annotation display. We also thank Mais Ammari, Rama Balakrishnan, Lionel Breuza, Leonardo Briganti, Fiona Broackes-Carter, Nancy Campbell, Karen Christie, Gayatri Chavali, Carol Chen, Maria Costanzo, Janos Demeter, Paul Denny, Robert Dodson, Harold Drabkin, Margaret Duesbury, Marine Dumousseau, Selina Dwight, Stacia Engel, Petra Fey, Dianna Fisk, Reija Hieta, Ursula Hinz, Marta Iannuccelli, Diane Inglis, Sruthi Jagannathan, Jyoti Khadake, Astrid Lagreid, Luana Licata, Paul Lloyd, Birgit Meldal, Anna Melidoni, Mila Milagros, Robert Nash, Li Ni, Sandra Orchard, Livia Perfetto, Pablo Porras Millan, Arathi Raghunath, Silvie Ricard-Blum, Bernd Roechert, Kim van Roey, Aleksandra Shypitsyna, Dmitry Sitnikov, Marek Skrzypek, Andre Stutz, Michael Tognolli and Edith Wong for additional contributions to the currently available annotation extension data set. The Gene Ontology Consortium is supported by National Human Genome Research Institute (NHGRI) U41 grant HG22073 to PIs JA Blake, JM Cherry, S Lewis, PW Sternberg and P Thomas. This grant supports all authors except those listed hereafter. RC Lovering, VK Khodiyar and T Sawford: British Heart Foundation grants SP/07/007/23671 and RG/13/5/30112. MA Harris, V Wood and A Lock: Wellcome Trust grant WT090548MA. Y Alam-Faruque: Kidney Research UK [RP26/2008] and European Molecular Biology Laboratory core funding. T Sawford and P Mutowo-Muellenet: NIH grant 4U41HG006104-04 to UniProt. K Van Auken: US National Human Genome Research Institute [U41-HG002223] and British Medical Research Council [G070119]. The work performed by H Dietze, S Carbon and CJ Mungall was additionally supported by the Director, Office of Science, Office of Basic Energy Sciences, of the U.S. Department of Energy under Contract No. DE-AC02-05CH11231. The article processing charge was funded by National Human Genome Research Institute (NHGRI) U41 grant HG22073. Authors’ contributions: All authors were involved in initial discussions on implementation of annotation extension and relationships. CJM, MAH, RPH, VW, ED, REF, DPH, RCL, YA-F, PM-M and JL defined the set of annotation extension relations currently in use. RPH, MAH, YA-F, ED, REF, DPH, VKK, AL, RCL, PM-M, KV-A and VW contributed annotations with extensions. TS was responsible for the development of Protein2GO to allow for curation of annotation extensions and for the graphical visualization of annotation extension relations. RPH coordinated the writing of the paper. RPH, MAH, JAB, DPH, JL, RCL, CJM, KV-A and VW contributed to the writing of the paper. SJC is responsible for the development of AmiGO2. HD worked on the OWLTools code for folding/unfolding. All authors read and approved the final manuscript.
Funding AgencyGrant Number
British Heart FoundationSP/07/007/23671
British Heart FoundationRG/13/5/30112
Wellcome TrustWT090548MA
Kidney Research UKRP26/2008
European Molecular Biology Laboratory (EMBL)UNSPECIFIED
Medical Research Council (UK)G070119
Department of Energy (DOE)DE-AC02-05CH11231
National Human Genome Research Institute (NHGRI)UNSPECIFIED
Subject Keywords:Gene Ontology, Functional annotation, Annotation extension, Manual curation
PubMed Central ID:PMC4039540
Record Number:CaltechAUTHORS:20140626-153759091
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Official Citation:Huntley et al.: A method for increasing expressivity of Gene Ontology annotations using a compositional approach. BMC Bioinformatics 2014 15:155.
Usage Policy:No commercial reproduction, distribution, display or performance rights in this work are provided.
ID Code:46541
Deposited By: Ruth Sustaita
Deposited On:27 Jun 2014 19:05
Last Modified:03 Oct 2019 06:45

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