Drafting a plan for pre-coordinating amerliorated an excacerbated phenotypes

[matentzn]

Apart from phenotypic abnormalities, ZFIN curates ameliorated and excacerbated phenotypes. These phenotypes are special in two senses

• they follow a simple pattern: biological attribute (tail length, glucose levels, eye morphology) in combination with a qualifier (ameliorated, exacerbated). They are simpler therefore than phenotypic abnormalities as they don't contain directions like "increased" and "decreased". (@ybradford could they be something like "blood glucose levels" with two entities involved, eg glucose part of blood?
• they don't automatically interact with "phenotypic abnormalities" hierarchically.

Now the problem is that (1) adding those into ZP will lead to two large branches with 3000 - 9000 terms being added (term proliferation), and (2) there is no integration between the two, or, indeed with anything in uPheno.

My sense is the ship to prevent term proliferation has sailed. We should just add these phenotypes the same way as the we have the others.

However, I do think we should move uPheno to the "changed" qualifier throughout so that we can group ameliorated, exacerbated and abnormal in a more general "phenotype" hierarchy.

[rays22]

I suspect that ameliorated and exacerbated are related to genetic suppression and enhancement, respectively. If that is the case, then they do imply a change of direction, however, the direction is relative, and not absolute, like increased or decreased, and the direction depends on the reference phenotype. The direction can be towards a normal, average, wild-type or other reference phenotypic state (genetic suppression --> ameliorated phenotype), or in the opposite direction (genetic enhancement --> exacerbated phenotype). Complete suppression reverts to a phenotype to normal, however, partial suppression and genetic enhancement should still be classed abnormal, or at least, deviation from a normal phenotypic state. For example, if a decreased eye size phenotype is partially ameliorated by some combination of genetic alterations, then it implies that the size of the eye still remains smaller (decreased) compared with the eyes of wild-type animals. decreased remains the qualifier in case of genetic enhancement, but the eye size decrease is exacerbated compared with an already abnormal state. Only complete genetic suppression reverts the phenotypic state to normal (assuming that that is the reference state). In my interpretation, ameliorated and exacerbated indicate that the reference phenotype is NOT the wild-type phenotypic state, but the reference is an abnormal (uPheno) phenotype. In my opinion they do/should interact with the phenotypic hierarchy.

Here is what I mean by genetic suppression and enhancement:

• genetic suppression: if a phenotype caused by a set of genetic alterations (a single allele, or a combination of alleles of one or more genes) is ameliorated when the original set of genetic alterations is combined with another set of genetic alterations (a single allele, or a combination of additional alleles of one or more additional genes), then it is a case of genetic suppression. Genetic suppression can be complete, when the abnormal phenotype reverts to completely normal, or partial, when the abnormal phenotype is not completely suppressed, but it changes in the direction of the normal or wild-type phenotype.
• genetic enhancement: if a phenotype caused by a set of genetic alterations (a single allele, or a combination of alleles of one or more genes) is exacerbated when the original set of genetic alterations is combined with another set of genetic alterations (a single allele, or a combination of additional alleles of one or more additional genes), then it is a case of genetic suppression. Genetic suppression can be complete, when the abnormal phenotype reverts to completely normal, or partial, when the abnormal phenotype is not completely suppressed, but it changes in the direction of the normal or wild-type phenotype.

[ybradford]

For ZFIN ameliorated and exacerbated phenotypes can be the result of genetic interactions or application of treatments (chemicals, drugs) or both.