The Gene Ontology: an evolution Jane Lomax

Gene Ontology: the grand-daddy of biomedical ontologies domian ontology - been around since about 1999 grass-roots ontology development effort amongst several model organism databases no biologists knew then what ontology meant 3 axes useful for capturing pertinent information about a gene product: what it does, where it acts, and the process it contributes to OBO format – OBO-Edit

Annotation The GO can’t be looked at in isolation from it’s annotations, which is what it was created for There are now a massive number, and which have been the key to its success In concert with developing the ontologies, a standard for annotation of genes and proteins to GO terms was developed which also required a level of evidence for the connection and various other pieces of data 17/01/2019

Barry’s favourite – menopause part-of death One of the features of the early GO was its relative simplicity – is_a and a completely unspecified part_of This made it very easy to write tools for, and combined with the simple annotation format, very easy for groups to start annotating immediately However, this simplicity also caused problems of its own further down the line – too simple to model many areas which lead to coding errors through misuse of is-a and part-of Barry’s favourite – menopause part-of death 17/01/2019

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Axioms Originally GO had no logical axoims Introduced by a process of reverse engineering: existing terms were text mined and mapped to either other GO terms or terms in other ontologies to create cross-product definitions (genus/differentia) – the same as EquivalentTo statements in OWL We’ve also developed other logical restrictions such as taxon constraints, disjoints and working towards standardization of the semantics of the annotation format 17/01/2019

Term Genie As more logical definitions and constraints get added to GO, it allows us to automate some previosuly manual editing processes Our new tool TermGenie allows terms that conform to specific templates to be added directly to the ontology by users 17/01/2019

Each template has slots that can be filled with ontology terms that have a defined relationship to each other. The slots are constrained such that only sensible terms are allowed. New terms get a real GO id instantly, but they go through a gatekeeper final vetting before being made live. 17/01/2019

The biggest effort has gone into creating cross-products that contain CHEBI terms. The idea was simple – define GO terms that reference chemicals in terms of a chemical ontology (CHEBI), and leverage their hierarchy to build those parts of GO In practice this process has taken several years and has highlighted several areas of fundamental differences in the way chemists and biologists view the world. This is a talk in itself – the good news is we have done it, more or less, and new GO chemical terms use CHEBI to be placed in the graph, and a full set of formal definitions using CHEBI are available. Chemicals 17/01/2019

Reasoning The size of GO has typically made reasoning difficult, but the newer fast reasoners like ELK have allowed us to start using reasoning much more in our pipelines. We use Jenkins, running the Hermit reasoner, to check the various GO files 17/01/2019

The future Annotation format massively restrictive – has lead to a bias towards pre-composition of term in the ontology – give example Some pre-coordination will always be desirable to limit the options available for annotation, but much more flexibility is desirible Also does not allow for linking annotations to provide context i.e. the execution of this function occurs during this process in this cc We’re looking to transition to a more expressive format 17/01/2019

Thanks GO ontology developers: Chris Mungall David Hill Tanya Berardini Rebecca Foulger Paola Roncaglia GO Consortium CHEBI developers 17/01/2019

Gene Ontology 2012 History 2000 – small, simple just is_a and part_of, no axoims. DAG-Edit application developed. Annotation begins. 2004 – move from GO ff format to OBO format. OBO-Edit released. 2006 – GO is_a complete 2009 – inter-ontology links 2010 – first axioms in GO 2011 - OBO-Edit moves to maintenance mode, editors use Protégé for reasoning 2011 – TermGenie available for adding terms to GO, leveraging axioms 2012 – First GO axioms referencing external ontology (CHEBI) 17 January 2019