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Model Annotation and Discovery With the Physiome Model Repository


Model Annotation and Discovery With the Physiome Model Repository

Dewan M Sarwar et al. BMC Bioinformatics.


Background: Mathematics and Phy sics-based simulation models have the potential to help interpret and encapsulate biological phenomena in a computable and reproducible form. Similarly, comprehensive descriptions of such models help to ensure that such models are accessible, discoverable, and reusable. To this end, researchers have developed tools and standards to encode mathematical models of biological systems enabling reproducibility and reuse, tools and guidelines to facilitate semantic description of mathematical models, and repositories in which to archive, share, and discover models. Scientists can leverage these resources to investigate specific questions and hypotheses in a more efficient manner.

Results: We have comprehensively annotated a cohort of models with biological semantics. These annotated models are freely available in the Physiome Model Repository (PMR). To demonstrate the benefits of this approach, we have developed a web-based tool which enables users to discover models relevant to their work, with a particular focus on epithelial transport. Based on a semantic query, this tool will help users discover relevant models, suggesting similar or alternative models that the user may wish to explore or use.

Conclusion: The semantic annotation and the web tool we have developed is a new contribution enabling scientists to discover relevant models in the PMR as candidates for reuse in their own scientific endeavours. This approach demonstrates how semantic web technologies and methodologies can contribute to biomedical and clinical research. The source code and links to the web tool are available at

Keywords: CellML; Epithelial transport; Model discovery; Physiome Model Repository; Semantic annotation.

Conflict of interest statement

The authors declare that they have no competing interests.


Fig. 1
Fig. 1
SemGen annotator interface of the sodium/hydrogen exchanger 3 (NHE3) [29] model where codewords identify CellML variables and we have annotated the sodium flux from proximal tubule to epithelial cell cytosol via the exchanger
Fig. 2
Fig. 2
Schematic diagram of synchronization between PMR workspaces as well as OpenCOR and SemGen with the provision of git
Fig. 3
Fig. 3
A composite annotation tree for sodium flux from proximal tubule to epithelial cell cytosol via sodium/hydrogen exchanger 3
Fig. 4
Fig. 4
A use case application to search for models in PMR which are relevant to the query ‘flux of sodium’. For convenience, we have displayed here top three components and the user can scroll down to see other components. By querying the knowledge in PMR this tool retrieves components from the NHE3 model [29], SGLT2 model [32], and the epithelial cell model [33]. Recommendations of models similar to the NHE3 model [29] are displayed as a result of the user selecting the NHE3 sodium flux in the returned results. See text for further details
Fig. 5
Fig. 5
Similarity matrix from the EBI Clustal omega service where protein with UniProt ID P26433 is in the selected model and the rest of the proteins are the basolateral membrane models shown in Fig. 4, (under the "Basolateral membrane model" heading) whose IDs and matrix scores are as follows: P48764 (89.49), Q9ET37 (21.86) and P06685 (18.20)

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    1. Hunter PJ, Borg TK. Integration from proteins to organs: the Physiome Project. Nat Rev Mol Cell Biol. 2003;4:237–43. doi: 10.1038/nrm1054. - DOI - PubMed
    1. Hunter P, Coveney PV, de Bono B, Diaz V, Fenner J, Frangi AF, Harris P, Hose R, Kohl P, Lawford P, McCormack K, Mendes M, Omholt S, Quarteroni A, Skår J, Tegner J, Thomas SR, Tollis I, Tsamardinos I, van Beek JHGM, Viceconti M. A vision and strategy for the virtual physiological human in 2010 and beyond. Philos Trans A Math Phys Eng Sci. 2010;368:2595–614. doi: 10.1098/rsta.2010.0048. - DOI - PMC - PubMed
    1. Nielsen PF, Nickerson DP. VPHi Webinar: Reproducibility and reuse in the Virtual Physiological Human. 2017. Accessed 24 Oct
    1. Neal ML, Cooling MT, Smith LP, Thompson CT, Sauro HM, Carlson BE, Cook DL, Gennari JH. A reappraisal of how to build modular, reusable models of biological systems. PLOS Comp Biol. 2014;10:1003849. doi: 10.1371/journal.pcbi.1003849. - DOI - PMC - PubMed
    1. Lister AL, Pocock M, Taschuk M, Wipat A. Saint: a lightweight integration environment for model annotation. Oxf Bioinforma. 2009;25:3026–7. doi: 10.1093/bioinformatics/btp523. - DOI - PMC - PubMed

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