Sensing the cilium, digital capture of ciliary data for comparative genomics investigations

Karen R. Christie, Judith A. Blake

Cilia are specialized, hair-like structures that project from the cell bodies of eukaryotic cells. With increased understanding of the distribution and functions of various types of cilia, interest in these organelles is accelerating. To effectively use this great expansion in knowledge, this information must be made digitally accessible and available for large-scale analytical and computational investigation. Capture and integration of knowledge about cilia into existing knowledge bases, thus providing the ability to improve comparative genomic data analysis, is the objective of this work. We focused on the capture of information about cilia as studied in the laboratory mouse, a primary model of human biology. The workflow developed establishes a standard for capture of comparative functional data relevant to human biology. We established the 310 closest mouse orthologs of the 302 human genes defined in the SYSCILIA Gold Standard set of ciliary genes. For the mouse genes, we identified biomedical literature for curation and used Gene Ontology (GO) curation paradigms to provide functional annotations from these publications. Employing a methodology for comprehensive capture of experimental data about cilia genes in structured, digital form, we established a workflow for curation of experimental literature detailing molecular function and roles of cilia proteins starting with the mouse orthologs of the human SYSCILIA gene set. We worked closely with the GO Consortium ontology development editors and the SYSCILIA Consortium to improve the representation of ciliary biology within the GO. During the time frame of the ontology improvement project, we have fully curated 134 of these 310 mouse genes, resulting in an increase in the number of ciliary and other experimental annotations. We have improved the GO annotations available for mouse genes orthologous to the human genes in the SYSCILIA Consortium's Gold Standard set. In addition, ciliary terminology in the GO itself was improved in collaboration with GO ontology developers and the SYSCILIA Consortium. These improvements to the GO terms for the functions and roles of ciliary proteins, along with the increase in annotations of the corresponding genes, enhance the representation of ciliary processes and localizations and improve access to these data during large-scale bioinformatic analyses.