= Phenotype Curation Guide =
== FYPO ==
 * Basic [wiki:FissionYeastPhenotypeOntology documentation] on wiki
 * Use the [https://github.com/pombase/fypo/issues FYPO tracker at Github] to request new terms

== Scope of phenotype curation ==
... especially when to curate phenotype, GO, or both
 * SGD's criteria (from Maria): "in summary, we annotate phenotypes that represent the effects of mutations on the organism as a whole, rather than the effects on the product of the gene that is mutated. For example, if a particular mutation blocks the in vitro activity of an enzyme, we might annotate that with GO but would not make a phenotype annotation. However, if the same mutation causes the inability of yeast to utilize a certain nutrient, then we would capture that as a phenotype annotation."
 * General !PomBase attitude: direct involvement or effects can usually be captured with GO terms, whereas indirect effects are better as phenotypes. We can pretty much always annotate an observed phenotype, but only a subset of phenotypes effectively support IMP-evidenced GO annotations.
  * example: tad3 subunit of tRNA adenosine deaminase - GO term for adenosine-to-inosine conversion; phenotype annotations for cell cycle arrest (PMID:17875641)

== Alleles ==
=== Names ===
  * wild type is yfg1+
  * if paper names it, use that name; otherwise:
   * deletions are named yfg1delta by default
   * if a deletion also has a marker inserted, you can use the name yfg1delta::ura4+
   * a disruption (different from a deletion, in that gene sequence, esp. coding, is still present) is yfg1::ura4+
   * everything else will just default to "noname" (displayed as "unnamed" on gene pages)
  * Additonal note: allele systematic ids will be gene systematic id dash integer, e.g. SPBC4.04c-2 SPBC4.04c-1, etc. and won't encode any details in identifier; stuff that info in properties, description, etc. 

=== Descriptions ===
 * See the built-in Canto hints and the [wiki:DescribingResidues page on describing residues] for how to specify allele descriptions
 * Choose "unknown" option in Canto if the change isn't described in the paper you're curating
  * If a description is entered in any Canto session, it will override an "unknown" description for the same allele name in any other session.
  * On gene pages, just the allele name will appear, with "unknown" in a mouseover

== Evidence ==
 * If there is no relevant evidence code, then find one in [https://evidenceontology.googlecode.com/svn/trunk/eco-edit.obo] and ask Kim to add it to the allowed list (affects Chado and the Canto interface).
 * If it doesn't exist request one from the evidence ontology: see http://code.google.com/p/evidenceontology/issues/list
 * If you use the "other" evidence code, you can put some specifics in a comment on the annotation.


== Conditions ==
 * Describes the experimental conditions which may or definitely affect the phenotype. Includes things such as:
  * Type of medium: rich medium, minimal medium, growth on agar plates, growth in liquid culture, glucose medium, sporulation medium etc
  * Chemicals added to the assay which are 'normally' not included in the medium, or which are added to the medium in a higher than normal concentration. This includes a wide range of substances: glutamate, cyclosporin A, calcium, hydrogen peroxide.
  * Chemicals added in a limiting amount (perhaps enough to get things going) but is then rapidly depleted by the cells. For instance adding 5 mg/L of adenine to the medium instead of 100 mg/L.
  * The temperature at which the cells were grown. Currently split into 3 categories; low, medium and high.
  * Sequential growth conditions, in which cells were subjected to a series of different conditions such as nitrogen starvation and recovery or heat shock and recovery.
 * Conditions live in a small in-house [https://github.com/pombase/fypo/blob/master/peco.obo ontology] in github. Request new condition terms on the [https://github.com/pombase/fypo/issues FYPO tracker].
 * Also see the [wiki:PrePostComposePhenotype page on pre- vs. post-composed FYPO terms]

== Annotation extensions ==
Phenotype annotations can have extensions to capture expressivity (severity), penetrance, and genes, transcripts or proteins used in an assay. Expressivity and penetrance can use qualitative values from the FYPO_EXT mini-ontology (in svn at pombe-embl/mini-ontologies/fypo_extension.obo), or penetrance can be specified quantitatively as a percent (I haven't run into any quantitative expressivity as of 2015-04-10 -mah).
 * Expressivity is usually qualitative, e.g. has_expressivity(FYPO_EXT:0000003) (note: FYPO_EXT:0000003 = low).  
 * Penetrance
  * Qualitative e.g. has_penetrance(FYPO_EXT:0000003)
  * Quantitative e.g. has_penetrance(25%)
 * Specifying what was assayed
  * 'Binding' phenotype terms
   * Binding to DNA, chromatin, small molecules
    * DNA binding FYPO:0000653 and descendants
     * assayed_using(geneA) strongly recommended
     * assayed_using(SO:nnnnnnn) optional, but recommended where possible
    * chromatin binding FYPO:0001093 - assayed_using(geneA) strongly recommended
    * small molecule binding, e.g. GTP binding FYPO:0001528 and descendants - assayed_using(geneA) strongly recommended; assumed if omitted
   * Protein binding - this is a special case because all of the things involved are gene products. Annotation extensions should therefore name both/all of the interacting proteins, whether or not that includes the mutated gene product. Canto should eventually require that each assayed_using() extension contains two or more gene/protein IDs. A check is run with each Chado load to flag any protein binding annotations that don't have two extensions (part of the chado_checks log). The Chado load also allows duplicated extensions specifically for the protein binding terms, in case a protein binding to itself is assayed.
    * mutation in geneA affects binding of protein A to protein B
     * assayed_using(geneA),assayed_using(geneB)
    * mutation in geneA affects binding of protein B to protein C
     * assayed_using(geneB),assayed_using(geneC)
    * mutation in geneA affects binding of protein A to protein B and protein C (three-way interaction)
     * assayed_using(geneA),assayed_using(geneB),assayed_using(geneC)
  * 'Catalytic activity' phenotype terms
   * Use assayed_enzyme to capture which gene product's activity was assayed
   * Use assayed_substrate to capture the substrate 
   * A catalytic activity phenotype annotation may have either or both of assayed_enzyme and assayed_substrate. It's less useful if the annotation has neither extension.
   * assayed_enzyme and assayed_substrate introduced March-April 2015. We've decided not to be too bothered about retrofitting extensions made with assayed_using prior to adding the new extension relations, because they're not wrong, they're just a bit less specific than is now possible.
  * Everything else (e.g. protein localization, protein level, RNA level, etc.) - assayed_using
   * e.g. assayed_using(PomBase:SPAC30D11.10)
 

=== FYPO annotation extension relations ===
These are in an [https://github.com/pombase/fypo/blob/master/supplemental_files/fypo_extension_relations.obo OBO file at github]. As of 2015-04-09:
 * has_expressivity - see above
 * has_penetrance - see above
 * assayed_using - see above
  * assayed_enzyme - see above
  * assayed_substrate - see above
 * occurs_in - rarely used; use with biological process phenotypes, usually with a Cell Ontology ID to capture when a phenotype is seen in one mating type but not the other
  * e.g. FYPO:0000821 occurs_in(CL:0002675)
 * is_bearer_of - rarely used, and a terrible kludge; use with colony pigmentation phenotypes to capture the colour
  * e.g. FYPO:0000741 is_bearer_of(PATO:0000322), where PATO:0000322 is "red"

== Additional notes ==
 * The [http://curation.pombase.org/pombe/docs/fypo_annotation Canto documentation on phenotype curation] has more information and examples.
 * Canto changes to capture phenotypes of double/triple mutants are in the testing phase now. In the meantime, we're alleles, phenotypes, etc. on the wiki or in files. Note: If the phenotype is "synthetic lethal" this is explicit in the BioGRID evidence code and can be inferred later from the interaction evidence, but we'll still need to make a note of the alleles.