Open Targets therapeutic areas: Gastrointestinal Disorders + Hepatobiliary Disorders

[paolaroncaglia]

Proposed TA name:

1. Gastrointestinal Disorders
2. Hepatobiliary Disorders Current EFO TA name: Digestive System Disease Priority for OT: High Justification: The gastrointestinal system and the hepatobiliary system have different physiological functions and should be separated. Specifically, liver events are important to flag for toxicology and safety assessments and should not be combined with gastrointestinal events

Gastrointestinal = pertaining to the stomach and intestine. https://medical-dictionary.thefreedictionary.com/gastrointestinal digestive = pertaining to digestion. digestive system the organs that have as their particular function the ingestion, digestion, and absorption of food or nutritive elements. They include the mouth, teeth, tongue, pharynx, esophagus, stomach, and intestines. The accessory organs of digestion, which contribute secretions important to digestion, include the salivary glands, pancreas, liver, and gallbladder https://medical-dictionary.thefreedictionary.com/digestive+system

Currently in EFO - Digestive System is sitting underneath the Anatomical structure [OLS views of 'digestive system' and 'liver disease' in EFO]

ACTION: Change name from “Digestive system disease” to “Gastrointestinal Disorders” Move “Hepatobiliary Disorder” up as a child of “disease by anatomical system”

[paolaroncaglia]

Summary for requested OT TAs Gastrointestinal Disorders + Hepatobiliary Disorders:

In EFO we already have MONDO:0002515 hepatobiliary disease Subclass of digestive system disease

As for gastrointestinal disorders, in EFO we have several children of digestive system disease that pertain to that area, e.g. Gastroesophageal disease Stomach disease Intestinal disease We don’t have a grouping term for gastrointestinal disorder. Neither has MONDO. We could create it, but I’m puzzled that UBERON doesn’t have a gastrointestinal system that we could map to. So we should either

• Consult with UBERON and MONDO and check if there’s any reason against having gastrointestinal system/disease; or,
• Instead of having gastrointestinal disorder as a TA, use the existing stomach disease (for gastric disease) and intestinal disease as TAs.

At any rate, in order for Gastrointestinal Disorders + Hepatobiliary Disorders to be directly under disease, we’d need to delete digestive system disease. But:

• digestive system disease is used by the GWAS Catalog, and deleting it would break GWAS’ pipeline. If we don’t delete it from EFO, we could give OT a slim that doesn’t contain it, but we’d still have to rehouse all of its children for the OT TAs to work; and GWAS would have no use for an “empty” digestive system disease.
• digestive system disease has mappings (database cross-references) to MeSH, ICD (9 and 10), NCIt, SNOMED, DOID, UMLS, plus MONDO and a couple more resources. If we delete it, those useful mappings are lost; if we make it childless, those mappings become meaningless.
• digestive system disease has 45 children in total. They need looking at to assess where they could be rehoused. This is a potentially useful exercise regardless of the final decision wrt TAs, but will take some time.

[zoependlington]

• [x] EFO:NEW1 gastrointestinal system

  • Child of digestive system
  • Definition of gastrointestinal system needs to be confirmed by Sandra to double check if FMA/UBERON are right/wrong, if it should be from mouth including intestines.

• [x] EFO:NEW2 gastrointestinal system disease

  • Subclass of digestive system disease
  • disease and (has disease location some (gastrointestinal system or (part_of some gastrointestinal system)))
    • Children of digestive system disease that do not fall under hepatobiliary disease need to be analysed to see if they can be reclassified to children of EFO:NEW2 or hepatobiliary disease.

[d0choa]

From MeSH:

Digestive system

MeSH link

A group of organs stretching from the MOUTH to the ANUS, serving to breakdown foods, assimilate nutrients, and eliminate waste. In humans, the digestive system includes the GASTROINTESTINAL TRACT and the accessory glands (LIVER; BILIARY TRACT; PANCREAS).

It contains:

• Gastrointestinal tract
• Biliary tract
• Liver
• Pancreas

Note: the definition specifies In humans. I'm assuming that's the reason why there might be some differences with UBERON.

Gastrointestinal tract

MeSH link

Generally refers to the digestive structures stretching from the MOUTH to ANUS, but does not include the accessory glandular organs (LIVER; BILIARY TRACT; PANCREAS).

The definition of the anatomical parts is also very close to what we want to achieve:

• Intestines
  • Intestinal Mucosa
  • Intestine, Large
  • Intestine, Small +
• Lower Gastrointestinal Tract
  • Ileum
  • Intestine, Large
  • Jejunum
• Mouth
  • Dentition
  • Salivary Glands
  • Tongue
• Pharynx
• Upper Gastrointestinal Tract
  • Duodenum
  • Esophagus
  • Stomach

[paolaroncaglia]

@d0choa and Sandra Thanks for your previous feedback on gastrointestinal + hepatobiliary disorders.

I think I’ve found the solution. The UBERON term we can refer to, as location for ‘gastrointestinal disorder’, is UBERON:0005409 ‘alimentary part of gastrointestinal system’, defined as “The part of the digestive system that excludes the hepatobiliary system”. That includes the mouth cavity but not the lips, which makes sense, so we would address the ‘mouth’ issue as well. And, UBERON:0005409 ‘alimentary part of gastrointestinal system’ is now in EFO as ‘gastrointestinal system’.

As for ‘hepatobiliary disorders’, we already have EFO MONDO:0002515 ‘hepatobiliary disease’. The only issue I see with your desired grouping is the placement of EFO:0009605 ‘pancreas disease’. If I understand correctly, you would like that to sit under ‘hepatobiliary disease’? In UBERON, the pancreatic system is not part of either gastrointestinal or hepatobiliary systems (it is part of digestive system and endocrine system); UBERON ‘pancreas’ is not connected to pancreatic system, nor to the digestive system. Because of its dual endocrine and exocrine functions, pancreas as a whole can’t be placed under one single parent without breaking ontology rules. However, if desired, we could make it part of the hepatobiliary system in the TA slim only, if that’s what’s needed? Please take a look at children of pancreas disease: e.g. diabetes mellitus would end up in the hepatobiliary TA (as well as under ‘endocrine system disease’).

Thanks, Paola

[d0choa]

Sounds great for the gastrointestinal disorder!

Regarding the pancreas, we don't want pancreas disease inside hepatobiliary disease. We would ideally aim for a solution like Mesh where digestive system disease has 3 different children being: gastrointestinal disease, hepatobiliary disease and pancreatic disease. We will select the 3 children as 3 separate therapeutic areas.

Meddra doesn't require an specific TA for pancreas as it separates the pancreatic diseases based on whether they are exocrine (going to gastrointestinal disease) or endocrine (endocrine system disease). However, we don't expect that level of detail from EFO and we can work with a dedicated pancreatic disease TA.

[paolaroncaglia]

@d0choa perfect, thanks!

[paolaroncaglia]

Note for self: issues in this ticket have been addressed via creation of an OT TA slim/profile.