Exploring autophagy with Gene Ontology

<p>Autophagy is a fundamental cellular process that is well conserved among eukaryotes. It is one of the strategies that cells use to catabolize substances in a controlled way. Autophagy is used for recycling cellular components, responding to cellular stresses and ridding cells of foreign material. Perturbations in autophagy have been implicated in a number of pathological conditions such as neurodegeneration, cardiac disease and cancer. The growing knowledge about autophagic mechanisms needs to be collected in a computable and shareable format to allow its use in data representation and interpretation. The Gene Ontology (GO) is a freely available resource that describes how and where gene products function in biological systems. It consists of 3 interrelated structured vocabularies that outline what gene products do at the biochemical level, where they act in a cell and the overall biological objectives to which their actions contribute. It also consists of ‘annotations’ that associate gene products with the terms. Here we describe how we represent autophagy in GO, how we create and define terms relevant to autophagy researchers and how we interrelate those terms to generate a coherent view of the process, therefore allowing an interoperable description of its biological aspects. We also describe how annotation of gene products with GO terms improves data analysis and interpretation, hence bringing a significant benefit to this field of study.</p

UniProtKB accession numbers for 29 homologous proteins using data from <i>in-situ</i> hybridisation expression in murine loop of Henle.

<p>Uniprot accession numbers are listed for homologues of the 29 proteins expressed in the murine loop of Henle structure (data provided by the GUDMAP Consortium via <a href="http://www.gudmap.org" target="_blank">www.gudmap.org</a>) as determined by BLAST (run via the uniprot.org website). The <i>Drosophila</i> proteins in parentheses are homologous to multiple mammalian proteins. (n/a = not applicable).</p

Summary of the number of GO terms significantly enriched in the differentially expressed gene dataset from glomeruli affected by Diabetic Nephropathy (DN) by both Ontologizer and GO-Elite enrichment analysis tools.

<p>A summary of the number of GO terms that were significantly enriched (having a p-value of <0.1) in the Baelde groups’ differentially expressed gene dataset from glomeruli affected by DN <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099864#pone.0099864-Baelde1" target="_blank">[29]</a> by both Ontologizer <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099864#pone.0099864-Bauer1" target="_blank">[28]</a> and GO-Elite <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0099864#pone.0099864-Zambon1" target="_blank">[27]</a> term enrichment tools, using the pre-annotation (2009) and post-annotation (2012) GO annotation datasets.</p

An OBO-Edit ‘Ontology Tree Editor’ view showing the 21 Gene Ontology terms representing renal development before the expansion in this area of the ontology.

<p>There were 18 GO terms directly under the ‘kidney development<i>’</i> node and 3 terms representing morphogenesis of the insect renal system, the Malpighian tubule (using the Gene Ontology file from November 18^th 2009). The [−] icon beside each term denotes no further child terms; (P) denotes a <i>part_of</i> relationship; (I) denotes an <i>is_a</i> relationship.</p

An OBO-Edit ‘Ontology Tree Editor’ view showing the relationship and position of the new GO term ‘<i>branching involved in ureteric bud morphogenesis</i>’.

<p>By placing the new term ‘<i>branching involved in ureteric bud morphogenesis</i>’ as a sub-type of ‘<i>morphogenesis of a branching structure’</i>, it puts the renal branching into the context of other types of branching morphogenesis within the Gene Ontology (using the Gene Ontology file from March 19^th 2012). The [+] icon beside each term denotes that there are further child terms that can be viewed; the [−] icon denotes no further child terms; (P) denotes a <i>part_of</i> relationship; (I) denotes an <i>is_a</i> relationship.</p

An OBO-Edit ‘Ontology Tree Editor’ view demonstrating the improved Gene Ontology representing ‘kidney development’ after a focused expansion.

<p>The Gene Ontology representing kidney development was enriched after a focused expansion with an additional 522 new terms, and as an example (using the Gene Ontology file from March 19^th 2012) the expanded node of the ‘<i>pronephros development</i>’ term shows it’s immediate child terms. The [+] icon beside each term denotes that there are further child terms that can be viewed; the [−] icon denotes no further child terms; (P) denotes a <i>part_of</i> relationship; (I) denotes an <i>is_a</i> relationship; (R) denotes a <i>regulates</i> relationship.</p

An OBO-Edit ‘Ontology Tree Editor’ view representing similarities in tubule structures and grouped terms describing the development of different types of renal tubules.

<p>Similarities are observed in GO terms representing tubule structures and terms are grouped together describing the development of different types of renal tubules including the Malpighian tubule of insects (using the Gene Ontology file from March 19^th 2012). The [+] icon beside a term denotes that the node is expandable and has further child/grandchild terms; the [−] icon denotes no further child terms; (P) denotes a <i>part_of</i> relationship; (I) denotes an <i>is_a</i> relationship.</p