Software:ApiNATOMY

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ApiNATOMY (logo, Fig.1) is a computational method that represents biological flow processes as circuits of graph edges, and biophysical structures that convey such processes as models of material conduits[1][2][3]. ApiNATOMY connectivity models (circuit assemblies of [a] conduits known as lyphs and [b] the processes that these conduits convey) are semantically annotated with ontological terms to create FAIR[4] topological models of flow from scenarios in normal physiology and disease (e.g. electrolyte control by the nephron, the regulation of peristalsis in the colon, the control of continence of the bladder, altered blood flow routes in the tetralogy of Fallot, altered cytosolic flow in complement attack).

The ApiNATOMY method represents biological pathways which, in the field of systems biology, has so far been primarily focused on databases depicting pathways of biochemical transformation from one molecular species to another (e.g.[5][6][7][8]). Specifically, ApiNATOMY manages knowledge about anatomical pathways that are represented in the form of conduit lyphs.

Development history

The evolution of the ApiNATOMY method to create biological connectivity models is outlined here and listed in the milestones table below.

Fig.2 Illustration of a primary Functional Tissue Unit, applied as a template (A) registered onto a central vessel (in this case, a capillary) to delineate a parcel of tissue (B) containing cells, and other structures, within diffusion distance of each other (C). Note the use of a treemap (D) to organise pFTU information over a whole-body map.

In brief, the ApiNATOMY originates with the identification of the primary functional tissue unit (pFTU, see Fig. 2)[9]. The pFTU was initially determined as a cylindrical tissue parcellation centred around a blood capillary in which any two points are within diffusion distance. Organizing pFTU knowledge over treemaps[10] (also in Fig.2) was a first approach to organise in ApiNATOMY whole-body flow-routes as established by physiology-based pharmacokinetic (PB-PK) methods.[11] Subsequent refinements to knowledge representation in ApiNATOMY included:

  • generalizing the definition of a pFTU to encompass any 80μm-diameter, 60μm-long cylindrical tissue parcel that longitudinally cuffs long-range exchange vessels consisting of either endothelium (i.e. conveying lymph or blood), mesothelium, surface epithelium or neuron[1];
  • extending the definition of conduit to any topologically-cylindrical biological structure (immaterial of scale) that conveys flow (i.e. the subcellular sodium pump, as well as an unbranched segment of the thoracic aorta, are both considered as conduits in ApiNATOMY)[2];
  • developing construction kit software[10][2] to build conduit models of complex, branched biological structures (see Fig.3).
Fig.3 A model of the urinary tree represented by a concatenation of edges representing urine flow, each edge conveyed by a layered model of a urinary conduit.
Milestones in ApiNATOMY development
Milestone (Year) Theme Description
1 (2012) Treemaps - Organizing the visual inspection of anatomy ontologies as tessellations to create visually-immediate and anatomically-meaningful treemap layouts representing regions of the mammalian body. [Ref.[10]]
2 (2013) Primary FTUs - Describing a primary functional tissue unit as a three-dimensional cylindrical block of cells centred around a capillary, such that each cell in this block is within diffusion distance from any other cell in the same block. [Ref.[9]]
3 (2013) Connectivity Routes
5 (2014) FTU Assemblies As Gatekeepers For Molecular Interaction - Proposing a hierarchical organisation to tissue architecture as secondary functional tissue units (sFTUs) in terms of molecular transport between contiguous primary FTUs via the endothelial or epithelial vessels. sFTUs represent units of physiological function that are replicated multiple times in a whole organ. [Ref.[1]]
6 (2016) Representing Processes In Pathophysiology Through Conduits - The formal representation of the pathophysiology mechanism in terms of correlations of rate and state measurements drawn from locations along and across conduit systems. [Ref.[2]]

References

  1. ↑ 1.0 1.1 1.2 Hunter, P. J.; de Bono, B. (2014-06-01). "Biophysical constraints on the evolution of tissue structure and function: Biophysical constraints on tissue evolution" (in en). The Journal of Physiology 592 (11): 2389–2401. doi:10.1113/jphysiol.2014.273235. PMID 24882821. PMC 4048097. http://doi.wiley.com/10.1113/jphysiol.2014.273235. 
  2. ↑ 2.0 2.1 2.2 2.3 de Bono, B.; Helvensteijn, M.; Kokash, N.; Martorelli, I.; Sarwar, D.; Islam, S.; Grenon, P.; Hunter, P. (2016-04-06). "Requirements for the formal representation of pathophysiology mechanisms by clinicians" (in en). Interface Focus 6 (2): 20150099. doi:10.1098/rsfs.2015.0099. ISSN 2042-8898. PMID 27051514. PMC 4759753. https://royalsocietypublishing.org/doi/10.1098/rsfs.2015.0099. 
  3. ↑ Cite error: Invalid <ref> tag; no text was provided for refs named :3
  4. ↑ Wilkinson, Mark D.; Dumontier, Michel; Aalbersberg, IJsbrand Jan; Appleton, Gabrielle; Axton, Myles; Baak, Arie; Blomberg, Niklas; Boiten, Jan-Willem et al. (December 2016). "The FAIR Guiding Principles for scientific data management and stewardship" (in en). Scientific Data 3 (1): 160018. doi:10.1038/sdata.2016.18. ISSN 2052-4463. PMID 26978244. PMC 4792175. http://www.nature.com/articles/sdata201618. 
  5. ↑ Kanehisa, Minoru; Furumichi, Miho; Sato, Yoko; Ishiguro-Watanabe, Mari; Tanabe, Mao (2021-01-08). "KEGG: integrating viruses and cellular organisms" (in en). Nucleic Acids Research 49 (D1): D545–D551. doi:10.1093/nar/gkaa970. ISSN 0305-1048. PMID 33125081. PMC 7779016. https://academic.oup.com/nar/article/49/D1/D545/5943834. 
  6. ↑ Bono, Bernard de; Vastrik, Imre; D’Eustachio, Peter; Schmidt, Esther; Gopinath, Gopal; Croft, David; Gillespie, Marc; Jassal, Bijay et al. (2007-12-01). "Reactome: An integrated expert model of human molecular processes and access toolkit". Journal of Integrative Bioinformatics 4 (3): 286–296. doi:10.1515/jib-2007-84. ISSN 1613-4516. https://www.degruyter.com/document/doi/10.1515/jib-2007-84/html. 
  7. ↑ Orchard, Sandra; Ammari, Mais; Aranda, Bruno; Breuza, Lionel; Briganti, Leonardo; Broackes-Carter, Fiona; Campbell, Nancy H.; Chavali, Gayatri et al. (January 2014). "The MIntAct project—IntAct as a common curation platform for 11 molecular interaction databases" (in en). Nucleic Acids Research 42 (D1): D358–D363. doi:10.1093/nar/gkt1115. ISSN 0305-1048. PMID 24234451. PMC 3965093. https://academic.oup.com/nar/article-lookup/doi/10.1093/nar/gkt1115. 
  8. ↑ Baltoumas, Fotis A.; Zafeiropoulou, Sofia; Karatzas, Evangelos; Koutrouli, Mikaela; Thanati, Foteini; Voutsadaki, Kleanthi; Gkonta, Maria; Hotova, Joana et al. (2021-08-20). "Biomolecule and Bioentity Interaction Databases in Systems Biology: A Comprehensive Review" (in en). Biomolecules 11 (8): 1245. doi:10.3390/biom11081245. ISSN 2218-273X. PMID 34439912. PMC 8391349. https://www.mdpi.com/2218-273X/11/8/1245. 
  9. ↑ 9.0 9.1 de Bono, Bernard; Grenon, Pierre; Baldock, Richard; Hunter, Peter (2013). "Functional tissue units and their primary tissue motifs in multi-scale physiology" (in en). Journal of Biomedical Semantics 4 (1): 22. doi:10.1186/2041-1480-4-22. ISSN 2041-1480. PMID 24103658. PMC 4126067. http://jbiomedsem.biomedcentral.com/articles/10.1186/2041-1480-4-22.   This article incorporates text available under the CC BY 2.0 license.
  10. ↑ 10.0 10.1 10.2 de Bono, Bernard; Grenon, Pierre; Sammut, Stephen John (May 2012). "ApiNATOMY: A novel toolkit for visualizing multiscale anatomy schematics with phenotype-related information" (in en). Human Mutation 33 (5): 837–848. doi:10.1002/humu.22065. https://onlinelibrary.wiley.com/doi/10.1002/humu.22065. 
  11. ↑ Thomas, Simon; Wolstencroft, Katherine; de Bono, Bernard; Hunter, Peter J. (2016-04-06). "A physiome interoperability roadmap for personalized drug development" (in en). Interface Focus 6 (2): 20150094. doi:10.1098/rsfs.2015.0094. ISSN 2042-8898. PMID 27051513. PMC 4759752. https://royalsocietypublishing.org/doi/10.1098/rsfs.2015.0094. 


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