Annotation Call December 9, 2014

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small conjugating enzyme ontology development (DavidH and Val)

1) The ontology edits are complete for all of the ubiquitin and other small conjugating enzymes. There are three parents: activating enzyme activity (E1), conjugating enzyme activity (E2) and ligase activity (E3)

2) Now all of the annotations for these need to be checked. We need a strategy for this re-annotation.

Checkpoint terms guidelines

Annotation to checkpoint terms is based partly on a priori knowledge that certain problems encountered by the cell lead to cell cycle arrest that is, at least in principle, reversible (provided that the problem encountered can be fixed). A checkpoint pathway comprises sensors which detect the problem, and signalling and effector molecules which function to negatively regulate a specific cell cycle transition.

Gene products should not be annotated to checkpoint terms based on mutations that result in activation of the checkpoint (i.e, cause cell cycle arrest). Such mutations cause a problem which is detected by the checkpoint sensor, and cell cycle arrest indicates that the checkpoint is functioning normally. This does not represent positive regulation of the checkpoint. The mutated gene itself is not necessarily part of the checkpoint in a normal cell (although some gene products are involved in both a cell cycle process and in a related checkpoint). For example, DNA replication defects due to mutations can result in DNA damage or stalled and collapsed replication forks, which can be recognised by a checkpoint sensor, but most gene products involved in DNA replication are not involved in the checkpoint. [add note about exception as an example?]

Gene products can be annotated to checkpoint terms when a mutation results in inactivation of the checkpoint. Such gene products may be the sensor (the first component of a checkpoint) or any component of the signalling pathway to the effector. Compromising the checkpoint means that mutations which would normally halt the cell cycle no longer do so.

Genes which are involved in correcting the problems detected by the checkpoint (e.g. DNA damage, spindle assembly defects) should not be annotated to the checkpoint terms, because they act downstream of the checkpoint itself. These genes should instead be annotated to "response to checkpoint x" terms, which are in a separate branch of the ontology.