Rare diseases

[paolaroncaglia]

Background: EFO agrees that representation of rare diseases is unsatisfactory; MONDO has already taken steps to rectify the situation (https://github.com/monarch-initiative/mondo/issues/254). EFO may want to adopt similar solutions (or align to MONDO altogether, to minimize inconsistencies that need time and effort to fix in EFO3). Open Targets already showed interest in an advanced solution (generate disease prevalence statements, #9).

To be sorted:

• [x] What's the structure in EFO now: As of 21/5/19, EFO has a multitude of 'Rare genetic x disease' ORDO terms under 'genetic disorder'. It also has many 'rare x' MONDO terms, e.g. 'rare teratologic disease', 'rare venous malformation' that are not in the 'Rare genetic x disease' branch.
• [x] What's the structure in MONDO now: As of 21/5/19, MONDO still has many 'rare' terms, e.g. 'rare hematologic disease'.
• [x] What axiom are MONDO using for 'rare': has modifier some rare, e.g. rare hematologic disease Subclass of: hematologic disease has modifier some rare See https://github.com/monarch-initiative/mondo/issues/254#issue-335897284 for details. (The child of 'disease characteristic' named 'rare or common', and its descendants 'rare' and 'not rare', are in MONDO and now in EFO3 too, and visible in OLS.)
• [x] 'rare' is already used in EFO3, but I assume that all its class usage cases in Protege (~900 of them) are for MONDO terms. @zoependlington could you confirm please?
• [ ] After the latest MONDO release, Zoe removed all the mappings to the terms that MONDO obsoleted, but those ORDO terms still exist in EFO. We may want to follow a similar strategy (when we clarify exactly what that was) and possibly starting from that same subset of ORDO terms. [This is now #452]
• [x] Not sure where MONDO stand in having completed their intended task (some 'rare' classes are still in MONDO). At our EFO-MONDO call in May, we agreed I'd ask Chris.
• [ ] Make a plan for prevalence statements (as requested in #9); keep MONDO in loop.

[paolaroncaglia]

@cmungall We're aware of this work in MONDO on obsoletion of rare-X terms: https://github.com/monarch-initiative/mondo/issues/254 That ticket is closed. However, we see that there are still some 'rare disease' terms in MONDO, see my comment above. Could you please explain what strategy you followed - e.g. did you start from rare genetic diseases first, and are leaving other 'rare' terms for later? We'd like to align on this work, not last because any significant change in MONDO will result in EFO errors after your release :-) Many thanks in advance!

[zoependlington]

@paolaroncaglia To answer:

'rare' is already used in EFO3, but I assume that all its class usage cases in Protege (~900 of them) are for MONDO terms. @zoependlington could you confirm please?

I can confirm all uses of 'rare' are in MONDO terms or EFO terms that have been mapped to MONDO terms and therefore inherited the 'rare' from the MONDO mapping.

[cmungall]

We obsoleted the ones for which there was a clear replacement, Rare X --> X, i.e. where we trivially shadow an existing class with a rare subclass

So ones like "rare disease with dentinogenesis imperfecta" remain, because we have no "disease with dentinogenesis imperfecta" (such a disease would already be rare I imagine)

I think we need to discuss these kinds of grouping classes (e.g. X with Y) separately. I think many could be obsoleted but this would be done in a very conservative way, in contrast to the Rare X --> X case.

On Wed, May 22, 2019 at 4:42 AM paolaroncaglia notifications@github.com wrote:

@cmungall https://github.com/cmungall We're aware of this work in MONDO on obsoletion of rare-X terms: monarch-initiative/mondo#254 https://github.com/monarch-initiative/mondo/issues/254 That ticket is closed. However, we see that there are still some 'rare disease' terms in MONDO, see my comment above. Could you please explain what strategy you followed - e.g. did you start from rare genetic diseases first, and are leaving other 'rare' terms for later? We'd like to align on this work, not last because any significant change in MONDO will result in EFO errors after your release :-) Many thanks in advance!

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[simonjupp]

Paola, can we compile a list of all the Rare X -> X that would be candidates for removal from EFO? We should check internally if any of these have been used for direct annotation and ensure there's a migration path for the downstream consumers.

[paolaroncaglia]

@cmungall thanks for explaining. @simonjupp I opened a ticket for that task, assigned it to me and linked it to this epic.

[paolaroncaglia]

Update on obsoleting (some) Orphanet 'rare x' diseases in EFO: part of this task will overlap with cleaning up undesired Orphanet-derived superclasses (Epic https://github.com/EBISPOT/efo/issues/322). That work is now scheduled for the first quarter of 2020 as it's top priority for Open targets.

[paolaroncaglia]

Update: we are still working on this in collaboration with Mondo; might be addressed in the second quarter of 2020 as part of the Orphanet work.

[paolaroncaglia]

Update: we're working with Mondo to address 'rare disease' terms that are still in Mondo and that Mondo already tagged as obsoletion candidates. Those are Orphanet-derived terms, so addressing them also addresses some Orphanet-derived parentage issues. In detail, Nicole and I have been working on this spreadsheet. Making a note here to

• [ ] Keep an eye on Mondo tickets labelled "EFO" and where title contains "rare". When Mondo has resolved on actions, see if EFO needs to edit those terms too.

[paolaroncaglia]

@zoependlington I haven't worked on disease terms since the time of my latest comment, but I know that Mondo has progressed steadily with its cleanup of 'rare disease' terms. The results of their work-in-progress should then all percolate to EFO eventually. Is this ticket still needed, and if yes, should it be updated?

[zoependlington]

Yes, any remaining rare terms should be Orphanet terms that will eventually be obsoleted/replaced by Mondo terms. There may be a few EFO terms that need looking into however, so this ticket should remain open.