Document the difference between the 4 released OWL files

[dhimmel]

EFO Release v3.25.0 contains the following OWL files:

• efo-base.owl 60.8 MB
• efo.owl 175 MB
• efo_otar_profile.owl 147 MB
• efo_otar_slim.owl 130 MB

I am curious as to how these files differ and haven't been able to find much information.

From an OpenTargets blog post:

we curated an extensive list of therapeutic areas that reflect the most appropriate body system, and therefore slimmed the ontology to ignore higher order terms (e.g. disease by anatomical system). The result is an EFO3-derived Open Targets Platform-specific profile-ontology which will be automatically generated with every monthly EFO release.

From opentargets/OnToma:

The ontology we use in the Open Targets platform is a subset (aka. slim) of the EFO ontology plus any HPO terms for which a valid EFO mapping could not be found.

Is there any other documentation I'm missing?

[ravwojdyla]

@dhimmel looking at the 3.11.0 release, the 1st release that contains those files there is some info:

For Open Targets, we have also generated an Open Targets profile (which contains all of EFO with the new Open Targets therapeutic areas) and slim file (which contains just Open Targets therapeutic areas). Both are also attached to this release.

[dhimmel]

EFO vs EFO-OTAR node comparison

I compared efo.owl and efo_otar_profile.owl from v3.25.0 and found that EFO-OTAR adds 10 nodes and removes 57 nodes from EFO.

Nodes added by EFO-OTAR

Here are the nodes EFO-OTAR adds (in purple outline) and their ancestors:

identifier	name	depth	n_ancestors	n_descendants	ic_resnik	ic_sanchez	uri
MONDO:0018797	None	5	6	1	0.98	1.00	http://purl.obolibrary.org/obo/MONDO_0018797
OTAR:0000010	respiratory or thoracic disease	4	5	1147	0.50	0.31	http://www.ebi.ac.uk/efo/OTAR_0000010
OTAR:0000019	familial disease	5	6	1	0.98	1.00	http://www.ebi.ac.uk/efo/OTAR_0000019
OTAR:0000008	other	4	5	1	0.98	1.00	http://www.ebi.ac.uk/efo/OTAR_0000008
OTAR:0000018	genetic, familial or congenital disease	4	5	7927	0.29	0.12	http://www.ebi.ac.uk/efo/OTAR_0000018
OTAR:0000003	cyst	5	6	1	0.98	1.00	http://www.ebi.ac.uk/efo/OTAR_0000003
OTAR:0000014	pregnancy or perinatal disease	4	5	120	0.71	0.53	http://www.ebi.ac.uk/efo/OTAR_0000014
OTAR:0000009	injury, poisoning or other complication	4	5	117	0.71	0.53	http://www.ebi.ac.uk/efo/OTAR_0000009
OTAR:0000017	reproductive system or breast disease	4	5	859	0.53	0.34	http://www.ebi.ac.uk/efo/OTAR_0000017
OTAR:0000006	musculoskeletal or connective tissue disease	4	5	3002	0.39	0.21	http://www.ebi.ac.uk/efo/OTAR_0000006

One question I have is what is the purpose of adding "familial disease", "other", "cyst", since these are all leaf nodes? Are they actually a helpful way for OpenTargets to categorize disease? CC @d0choa. MONDO:0018797 also has no descendants, but appears to be a relic, soon to be removed, as per https://github.com/EBISPOT/efo/issues/938.

Nodes removed by EFO-OTAR

Here are the nodes EFO-OTAR removes (in purple outline) and their ancestors:

Expand for removed nodes table

identifier	name	depth	n_ancestors	n_descendants	ic_resnik	ic_sanchez	uri
MONDO:0044999	scalp disease	7	8	8	0.95	0.80	http://purl.obolibrary.org/obo/MONDO_0044999
MONDO:0021017	synaptopathy	6	7	13	0.93	0.75	http://purl.obolibrary.org/obo/MONDO_0021017
MONDO:0019038	rare maxillo-facial surgical disease	8	16	222	0.75	0.47	http://purl.obolibrary.org/obo/MONDO_0019038
MONDO:0043786	serositis	5	6	10	0.94	0.77	http://purl.obolibrary.org/obo/MONDO_0043786
MONDO:0044974	disease of supramolecular complex	6	7	389	0.62	0.42	http://purl.obolibrary.org/obo/MONDO_0044974
MONDO:0021635	neurocristopathy	5	8	134	0.75	0.52	http://purl.obolibrary.org/obo/MONDO_0021635
MONDO:0044969	disease of membrane bound organelle	6	7	403	0.62	0.41	http://purl.obolibrary.org/obo/MONDO_0044969
MONDO:0021668	disorder involving pain	4	5	13	0.90	0.75	http://purl.obolibrary.org/obo/MONDO_0021668
EFO:1000755	pigmentation disease	6	11	117	0.78	0.53	http://www.ebi.ac.uk/efo/EFO_1000755
MONDO:0044980	disease of signal transduction	6	7	125	0.73	0.53	http://purl.obolibrary.org/obo/MONDO_0044980
MONDO:0044979	disease by cell type	6	7	506	0.60	0.39	http://purl.obolibrary.org/obo/MONDO_0044979
MONDO:0021197	disease by cellular component affected	5	6	1339	0.49	0.29	http://purl.obolibrary.org/obo/MONDO_0021197
MONDO:0024623	otorhinolaryngologic disease	6	7	337	0.64	0.43	http://purl.obolibrary.org/obo/MONDO_0024623
MONDO:0044975	disease of transporter activity	6	7	74	0.77	0.58	http://purl.obolibrary.org/obo/MONDO_0044975
MONDO:0024627	phagocytic cell dysfunction	7	8	47	0.83	0.62	http://purl.obolibrary.org/obo/MONDO_0024627
MONDO:0002436	nasal disorder	7	10	40	0.89	0.64	http://purl.obolibrary.org/obo/MONDO_0002436
MONDO:0021073	paraneoplastic syndrome	5	6	9	0.93	0.78	http://purl.obolibrary.org/obo/MONDO_0021073
MONDO:0018652	biological anomaly without phenotypic characterization	5	6	4	0.96	0.86	http://purl.obolibrary.org/obo/MONDO_0018652
MONDO:0044989	foot disease	6	7	10	0.93	0.77	http://purl.obolibrary.org/obo/MONDO_0044989
MONDO:0044987	face disease	7	8	1719	0.50	0.27	http://purl.obolibrary.org/obo/MONDO_0044987
MONDO:0020683	acute disease	4	5	89	0.75	0.56	http://purl.obolibrary.org/obo/MONDO_0020683
MONDO:0021195	disease by cellular process disrupted	5	6	2008	0.45	0.25	http://purl.obolibrary.org/obo/MONDO_0021195
EFO:0000524	head and neck disorder	5	6	2103	0.45	0.25	http://www.ebi.ac.uk/efo/EFO_0000524
EFO:0009470	soft tissue disease	4	5	124	0.72	0.53	http://www.ebi.ac.uk/efo/EFO_0009470
MONDO:0024317	chronic pain syndrome	5	6	6	0.95	0.82	http://purl.obolibrary.org/obo/MONDO_0024317
EFO:0000405	digestive system disease	5	6	1236	0.51	0.30	http://www.ebi.ac.uk/efo/EFO_0000405
MONDO:0021670	post-infectious syndrome	5	7	2	0.99	0.93	http://purl.obolibrary.org/obo/MONDO_0021670
MONDO:0017368	systemic disease with skin involvement	6	7	42	0.83	0.63	http://purl.obolibrary.org/obo/MONDO_0017368
MONDO:0021196	disease by molecular activity disrupted	5	6	251	0.65	0.46	http://purl.obolibrary.org/obo/MONDO_0021196
Orphanet:79389	Premature aging	5	6	83	0.75	0.57	http://www.orpha.net/ORDO/Orphanet_79389
MONDO:0021147	disorder of development or morphogenesis	4	5	3827	0.36	0.19	http://purl.obolibrary.org/obo/MONDO_0021147
MONDO:0044977	disease of receptor activity	6	7	7	0.95	0.81	http://purl.obolibrary.org/obo/MONDO_0044977
MONDO:0017261	systemic diseases with panuveitis	6	7	6	0.96	0.82	http://purl.obolibrary.org/obo/MONDO_0017261
EFO:0009714	chronic disease	4	5	107	0.73	0.54	http://www.ebi.ac.uk/efo/EFO_0009714
MONDO:0021674	post-viral disorder	5	6	56	0.79	0.61	http://purl.obolibrary.org/obo/MONDO_0021674
MONDO:0002254	syndromic disease	4	5	2541	0.39	0.23	http://purl.obolibrary.org/obo/MONDO_0002254
MONDO:0021673	post-bacterial disorder	5	6	1	0.98	1.00	http://purl.obolibrary.org/obo/MONDO_0021673
EFO:0009903	inflammatory disease	4	5	597	0.57	0.37	http://www.ebi.ac.uk/efo/EFO_0009903
MONDO:0021199	disease by anatomical system	4	5	10922	0.27	0.09	http://purl.obolibrary.org/obo/MONDO_0021199
MONDO:0005042	head disease	6	7	2012	0.47	0.25	http://purl.obolibrary.org/obo/MONDO_0005042
MONDO:0024626	defective phagocytic cell engulfment	6	10	8	0.96	0.80	http://purl.obolibrary.org/obo/MONDO_0024626
MONDO:0044971	disease of macromolecular complex	6	7	155	0.72	0.51	http://purl.obolibrary.org/obo/MONDO_0044971
MONDO:0020595	disease of retroperitoneum	6	7	18	0.94	0.72	http://purl.obolibrary.org/obo/MONDO_0020595
EFO:0009479	throat disease	6	7	1	0.99	1.00	http://www.ebi.ac.uk/efo/EFO_0009479
MONDO:0017259	systemic diseases with anterior uveitis	6	7	13	0.92	0.75	http://purl.obolibrary.org/obo/MONDO_0017259
MONDO:0021016	channelopathy	7	8	57	0.81	0.60	http://purl.obolibrary.org/obo/MONDO_0021016
MONDO:0044965	abdominal and pelvic region disorder	5	6	977	0.53	0.32	http://purl.obolibrary.org/obo/MONDO_0044965
MONDO:0020012	systemic or rheumatic disease	4	5	312	0.62	0.44	http://purl.obolibrary.org/obo/MONDO_0020012
MONDO:0024505	disorder by anatomical region	4	5	4746	0.35	0.17	http://purl.obolibrary.org/obo/MONDO_0024505
MONDO:0015938	systemic disease	5	6	257	0.65	0.46	http://purl.obolibrary.org/obo/MONDO_0015938
MONDO:0044976	disease of catalytic activity	6	7	173	0.70	0.49	http://purl.obolibrary.org/obo/MONDO_0044976
MONDO:0017260	systemic diseases with posterior uveitis	7	8	4	0.98	0.86	http://purl.obolibrary.org/obo/MONDO_0017260
EFO:0009664	disease of orbital region	6	9	1481	0.52	0.28	http://www.ebi.ac.uk/efo/EFO_0009664
MONDO:0044967	limb disorder	5	6	69	0.78	0.58	http://purl.obolibrary.org/obo/MONDO_0044967
MONDO:0044990	hand disease	6	7	6	0.95	0.82	http://purl.obolibrary.org/obo/MONDO_0044990
EFO:0001058	sensory system disease	6	7	291	0.64	0.44	http://www.ebi.ac.uk/efo/EFO_0001058
MONDO:0021194	disease by subcellular system affected	4	5	2901	0.40	0.22	http://purl.obolibrary.org/obo/MONDO_0021194

Code

Code to produce these figures and tables is not yet available, but is based on nxontology. I hope to make the nxontology importer for EFO available soon.

[d0choa]

Thanks @dhimmel for the analysis. It's really useful. @zoependlington can provide more details.

From the Open Targets perspective, the background story behind the slim was that we wanted to align EFO to a more clinical interpretation. EFO has a lot of high-level organisational nodes that attend to anatomical characteristics (many of them can be seen on your analysis). However, they have little or no clinical value (e.g. disease by anatomical system). Instead, the top-nodes of the slim resemble other clinical classifications like Meddra.

In the process of reorganising the terms, a few terms have to be removed, relocated or split. You can find the logic behind most of the changes in the respective tickets. For the ones that you raised I found the next:

• Familial disease. In this case, I believe the term was not populated. The ticket describes the actions to take but it's still open and probably never implemented.
• Cyst. I suspect this is a similar issue. The Cyst term was never populated with the many cyst-related diseases contained in EFO.

@paolaroncaglia and @zoependlington can comment on these two.

Regarding Other, it's a placeholder for newly introduced terms in EFO that have no parentage relationship in the slim. We aimed to have it empty, as all diseases should be children of other root level terms (therapeutic areas). You can consider it an artefact of the process and we should eventually remove it.

[dhimmel]

Quoting @zoependlington from https://github.com/EBISPOT/efo/issues/927#issuecomment-760762229 regarding forced relationships in EFO-OTAR:

The forced relationships are defined in the subclasses templates file found in the temporary/working home of OTAR_profiler here: https://github.com/EBISPOT/otar_profiler

Just a note that the "final" version for use by Open Targets is the slim file, which only contains the therapeutic areas that are useful for annotating their data. The profile is our master EFO with a few extra terms, which will eventually be added to the master EFO file once we have completed the ongoing work with our profile and slim files to be compatible with the Open Targets pipelines and their needs.

Great to know about EBISPOT/otar_profiler. I see that otar_ta.sh is the script that creates efo_otar_profile.owl and efo_otar_slim.owl. allTAs.txt contains a list of therapeutic areas and newterms.tsv contains nodes added by EFO-OTAR.

Based on otar_ta.sh, it looks like efo_otar_slim.owl is derived from efo_otar_profile.owl by filtering to therapeutic areas and their descendants (via robot MIREOT --branch-from-terms. So this is is useful for OpenTargets which wants a hierarchy of diseases only without other parts of the ontology?

Regarding "the profile is our master EFO with a few extra terms, which will eventually be added to the master EFO file", does that mean the eventual plan is to take all the modifications in efo_otar_profile.owl and move them upstream to efo.owl? If so, does that mean efo_otar_profile.owl might eventually go away, because it would be the same as efo.owl? And does this also mean EFO intends to remove the "organisational nodes that attend to anatomical characteristics" in favor of EFO-OTAR's "clinical interpretation"?

Getting back to the original documentation request, it would be nice to have guidance in the README regarding when to use efo-base.owl, efo.owl, efo_otar_profile.owl, versus efo_otar_slim.owl. My current understanding is:

1. efo-base.owl: use if you only want terms from the EFO namespace (subClassOf relationships might be incomplete?)
2. efo.owl: use if you want the primary EFO release with terms from the EFO namespace and those imported from other ontologies
3. efo_otar_profile.owl: use if you want the complete ontology, with modifications introduced by OpenTargets, which might eventually be adopted in efo.owl.
4. efo_otar_slim.owl: use if you want an ontology of diseases rooted to therapeutic areas, as defined and used by OpenTargets

Is this understanding correct?