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To: Members of the SOFG-Definitions Group From: Cornelius Subject: Definition of Anatomical Structure Date: January 24, 2005 Comments: February 7, 2005 [cjm] Comments: February 15, 2005 [mah] Comments: February 15, 2005 [sel] The validity of all the FMA definitions relating to cell and cell parts depends on the definition of the genus of Cell: Anatomical structure. All the entities we have to define in our working group fall into subclasses of Anatomical structure; i.e., they are all anatomical structures. This term is used with many different meanings in traditional and in silico source; e.g., some of these sources regard a space such as the pleural cavity, as an anatomical structure. Therefore, I feel it is important that we should be clear at the outset about what we mean by this term and we should be in agreement. The FMA definition is: Anatomical structure Material physical anatomical entity which has inherent 3D shape; is generated by coordinated expression of the organism's own structural genes; its parts are spatially related to one another in patterns determined by coordinated gene expression. Examples: heart, right ventricle, mitral valve, myocardium, endothelium, lymphocyte, fibroblast, thorax, cardiovascular system, hemoglobin, T cell receptor, gene. I don’t think gene is an example of anatomical structure! Perhaps a gene product such a protein or RNA molecule. I completely agree with Chris on this one. There are certainly regions on a chromosome that are inherited, and are associated with certain physical products in the cell (transcripts and proteins). The extent of these regions however is not clear-cut however, and I think it better to stay with concrete physical entities for which the boundaries are inarguable. One of the tenets of FMA is the strict organizing relationships. It would be good to state that here. I’m also wondering if you might want to (somewhere) mention the cell ontology. At least to provide the rationale for including everything from the gross morphological level to the molecular. Comment: 1. Let us disregard the genus [Material physical anatomical entity, which means that the entities in this class have volume and mass, unlike spaces, which have volume but no mass] and deal with each of the differentia: a. has inherent 3D shape. Unlike liquids [blood, urine], which also have volume and mass, anatomical structures are solid/semisolid [gel] objects, which have their own shape, unlike liquids, which adapt to the shape of their container. I’m not quite sure why you have excluded liquids though, Plasma consists of many proteins; blood contains cells. Surely these are things we would want to include. The biologists I ask here consider blood, plasma, milk, semen, etc. all as tissues. 1 b. is generated by coordinated expression of the organism's own structural genes. This differentia distinguishes anatomical structures from inanimate objects [bullets, prostheses] and foreign organisms and their parts [parasite, transplant] located in an organism. This should lead us to consider what is the smallest or most primitive object that qualifies as an anatomical structure, but let us defer that. Can you define “structural” in the context of genes? Would we want to exclude a transplanted organ? Barry has (quite rightly) always argued against circular definitions. The definition above for “Anatomical structure” includes the adjective “anatomical”. It would be nice to remove this. If we do, then the definition has to carefully limit the scope, so that things like a bird’s nest, or the by products of sugar metabolism aren’t included (they are 3-D and physical and the organism produced them) c. its parts are spatially related to one another in patterns determined by coordinated gene expression. This differentia excludes from the class Anatomical structure a sediment of blood cells, a rouleau, or the “buffy coat”. These properties (a-c) are shared by a biological macromolecule, a mitochondrion, a cell, a tissue, and the other things we have to define. These entities inherited these properties from their superclass in the taxonomy. This definition includes molecules, even small molecules, because these are generated by coordinated gene expression (maybe we have to define coordinated gene expression?). Is this problematic? Most people would not think of “arginine” as an anatomical stucture; I don’t see how [c] would exclude this. Should there be a “minimal granularity” beyond which it is no longer anatomical? This definition is dependent on the definition of “gene”. This is notoriously problematic. Is there a different way to word the definition? Maybe just changing it to “gene products”. Even then, it seems problematic. Many structures are formed from a combination of genes and environment. It would seem odd to include “termite nest” as an anatomical structure, but I’m not sure what is to stop a machine reasoning otherwise! (ha-ha, Chris and I were thinking the same thing) The “own” is problematic in “coordinated expression of the organism’s own structural genes”. What about maternal effect genes? Yes, I agree. We must account for maternal effect genes. The egg is a big thing (usually) and the products from the mother that are in the cytoplasm have to be accounted for. There are other situations as well I agree, I think we need to avoid the use of the term “gene.” Let’s think about our purpose here, which I understand is to generate cross species definitions for anatomical terms. Do we really want our ontologies to be populated with genes, proteins, and protein complexes? I too do not think 2 of these things as anatomical structures, though they are certainly required for anatomical structures to develop and be maintained. Perhaps a definition that limits anatomical structures to be comprised of one or more cells would work? 2. Such inheritance of attributes [characteristics, properties and differentia] is a critical requirement that definitions have to meet, if the intent is to construct a taxonomy or ontology [ultimately]. A dictionary, such as Stedman’s, is not constrained by such requirements. Unlike dictionary definitions, each of the FMA definitions on its own is incomplete. It is competed by the definition of each of the ancestors of any given class in the taxonomy. 3. I realize that you may not want to set such aims for the definitions we have to generate, since our immediate objective seems to be to reach consensus among ourselves about the meaning of given terms. I suggest that it would be a mistake to limit our task in such a way. We should be able to have our cake and eat it. Yes, let’s have both dictionary and formal defs, but we should be careful to separate them. 4. Finally, note that Anatomical structure may be a better genus for Cell than “The smallest unit of living structure”. We may argue about what that smallest structure might be. But even if we agree, where would we put smallest unit of living structure in an ontology or taxonomy? Would other classes of the ontology subsume petite, M, L, XL, XXL sizes of anatomical entities? What about keeping the def structural; eg “Material physical entity which has inherent 3D shape and is part of (or the whole of) an organism” . Would obviously require precise definition of organism. (One that takes into account unusual organisms like dictostelium….). Anatomy comes from the latin anatomia, meaning dissection; ana=up and tome=a cutting; cutting up of the body. With this in mind, a definition of anatomical structure would imply that one could isolate that structure physically on a gross level. Perhaps subcellular structures, including genes and their products, could be described by “microscopic anatomical structures” or “subcellular anatomical structures,” which really comprise a different subject. 3