Ontology subsumption reasoning.

<p>This example from Washington et al. <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000374#pbio.1000374-Washington1" target="_blank">[23]</a> shows the relationships of the term “intestinal epithelium” to other anatomical entities within the ZFA ontology. Gray arrows with an “i” indicate an is-a relation, and blue arrows with a “p” indicate a part-of relation. The numbers indicate IC of the node, which is the negative log of the probability of that description being used to annotate a gene, allele, or genotype (collectively called a feature). As terms get more general, reading from bottom to top, they have a lower IC score because the more general terms subsume the annotations made to more specific terms.</p

Typical structures of ontologies.

<p>Almost all biomedical ontologies are either simple tree structures that represent hierarchical classifications or directed acyclic graphs (DAGs). The difference is that the latter allows a term to be related to multiple broader tems (green arrows) whereas the former does not. Directed cyclic graphs are very rarely used for ontologies; the reason is that cycles (red arrows) can only arise in ontologies that make use of other relationships than <i>is-a</i> and <i>part-of</i> are used <a href="http://www.plosbiology.org/article/info:doi/10.1371/journal.pbio.1000374#pbio.1000374-Aranguren1" target="_blank">[28]</a>. We illustrate each structure with simplified examples, namely an ontology of vertebrates, an ontology of cellular components, and an ontology of cell-cycle regulation that shows the mutual regulation of cyclin-dependent kinase (CDK) and anaphase-promoting complex/cyclosome (APC/C).</p

The growth of ontologies in biomedicine.

<p>To illustrate the increasing use of ontologies, we mined PubMed abstracts for occurrences of the words <i>ontology</i> and <i>gene ontology</i> (and the plural forms thereof). We normalized for the general growth of PubMed by converting the raw counts per year to “hits per million abstracts.” The plot shows a steady increase in the awareness of ontologies over the past decade, and that GO became the dominating biological ontology over a period of just five years (note the logarithmic scale). However, ontologies appear to have reached a plateau over in the past three years, at least in terms of how often they are mentioned in abstracts. In contrast, the citations to GO and associated resources are steadily rising (end of 2009>5500) and imply a further increasing use.</p

Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?-0

Co-directional overlapping pairs longer than 60 bps classified in each group is shown. Gene a represents the upstream gene, while gene b represents the downstream gene. In Fragmentation type gene x, y and z represent the orthologs of gene a and b.<p><b>Copyright information:</b></p><p>Taken from "Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?"</p><p>http://www.biomedcentral.com/1471-2164/9/335</p><p>BMC Genomics 2008;9():335-335.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2478687.</p><p></p

Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?-3

Co-directional overlapping pairs longer than 60 bps classified in each group is shown. Gene a represents the upstream gene, while gene b represents the downstream gene. In Fragmentation type gene x, y and z represent the orthologs of gene a and b.<p><b>Copyright information:</b></p><p>Taken from "Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?"</p><p>http://www.biomedcentral.com/1471-2164/9/335</p><p>BMC Genomics 2008;9():335-335.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2478687.</p><p></p

Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?-2

Ransferase) genes among Enterobacteria. A) Multiple alignment of the C-terminal of the DNA polymerase psi subunit and the N-terminal of the alanine acetyltransferase protein among Enterobacteria species. The grey boxes indicate the fragments that are encoded in the overlapping region between and genes. The alignments of Escherichia & Shigella, Salmonella and Yersinia are marked. B) Arrangement of overlapping regions and amino acid conservation within the overlap among K12, Ty2 and CO92. The nucleotide consensus shows an asterisk for the conserved nucleotides and a dot for the not conserved. Although we chose one species of each group marked in part A (Escherichia & Shigella, Salmonella and Yersinia) we can observe the high similarity at the level of sample nucleotide sequences too.<p><b>Copyright information:</b></p><p>Taken from "Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?"</p><p>http://www.biomedcentral.com/1471-2164/9/335</p><p>BMC Genomics 2008;9():335-335.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2478687.</p><p></p

Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?-1

Contribute a disproportionate number of overlapping pairs to the misannotations. In the figure we can see the 5 species that accumulate more misannotations.<p><b>Copyright information:</b></p><p>Taken from "Large gene overlaps in prokaryotic genomes: result of functional constraints or mispredictions?"</p><p>http://www.biomedcentral.com/1471-2164/9/335</p><p>BMC Genomics 2008;9():335-335.</p><p>Published online 15 Jul 2008</p><p>PMCID:PMC2478687.</p><p></p

Schematic Representation of the Procedure Employed to Classify the Three Major Types of Genes and Derived Sequences Identified in Human and Mouse According to Their Origin between and within Each Species

<p>Dashed boxes denote key action steps in the procedure. See text for details.</p

Uncharacterized operon related to cell envelope biogenesis.

<p>Species tree with family representatives and corresponding operon architecture. COG1259 (containing the hypothetical gene rv1829 (red unit)) evidentially linked to several uncharacterized genes (variably colored units) to COG0558 (containing PsgA2: Phosphatidylglycerophophate synthase (dark blue unit)).</p

Uncharacterized gene linked to vitamin B5 and B9 biosynthesis pathways.

<p>(A) Species tree with family representatives and corresponding operon architecture. COG4595 (containing the hypothetical gene rv3603c (red unit)) evidentially linked to several genes of pantothenate (vitamine B5) biosynthesis pathway (variably colored units upstream the red unit) and to folic acid (vitamine B9) biosynthesis pathway (downstream the red unit). (B) Pathway of pantothenate biosynthesis related to KEGG database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0034302#pone.0034302-Kanehisa1" target="_blank">[38]</a>. (C) Detailed illustration of the essential genes of the vitamine B5 biosynthesis operon.</p