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callahantiff / PheKnowLator

PheKnowLator: Heterogeneous Biomedical Knowledge Graphs and Benchmarks Constructed Under Alternative Semantic Models
https://github.com/callahantiff/PheKnowLator/wiki
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KG V2.0.0 - Finalizing Knowledge Representation #17

Closed callahantiff closed 4 years ago

callahantiff commented 4 years ago

Extending Knowledge Representation for current KG

Current Release: v2.0.0

Description
Adding the following entities/data sources to the current KG build:

TODO πŸ“‹ πŸ’» πŸ“

@callahantiff Due Dates:

ignaciot commented 4 years ago

Also:

protein-complex, RO_0002436

callahantiff commented 4 years ago

Also:

protein-complex, RO_0002436

Good catch, I will add to the original issue, thanks!

callahantiff commented 4 years ago

@ignaciot and @bill-baumgartner - the updated KR is shown below (click on image to enlarge). Note that the main data types are ontologies (yellow), open data sources (purple), and experimental data (blue). Note, that this has been verified by Adrianne as well.

Screen Shot 2019-11-25 at 09 57 47

You will notice that I have added the cell ontology and BRENDA in addition to experimental data in order to satisfy a component of my comps -- creating a KG, which actually includes the central dogma. GTEx is a great source to start with since it includes many disease types and has the results of both microarray and RNA-seq (for several types of samples), and includes connections to phenotypes.

Anywho, happy to talk about this more this afternoon!

ignaciot commented 4 years ago

This is fantastic! Yes, let’s chat this afternoon.

callahantiff commented 4 years ago

UPDATES: Incorporating feedback from @bill-baumgartner and @LEHunter resulted in the updated KR shown below.

Screen Shot 2019-11-26 at 12 31 57

Some important questions that I would like help answering:

  1. @ignaciot - you've asked that I use the relation molecularly interacts with and the definition of this relation includes alternative terms, which specify that this relation specifically means binding interactions.
    • Did you intend it to be used that way?
    • If you did intend this relation be used then it might make sense to change the protein-protein and gene-gene interactions (or at least the gene-gene interactions) to genetically interacts with -- @LEHunter, thoughts?


  1. @LEHunter - @bill-baumgartner and I were talking about the possibility of adding the inverse properties. What are your thoughts on this? Do you think it would have negative ramifications for things like random walk?


  1. @bill-baumgartner - I kept the edge causally influences. I was unable to find anything in the RO for options like alters or has variant.


  1. Any other errors or anything weird that needs editing?


  1. I'd like to substitute the following BFO terms for the proposed RO terms, do you agree?:
ignaciot commented 4 years ago

Yup, that is the reason I chose molecularly interacts with (binding). Looking at the definition of that other relation (An interaction that holds between two genetic entities (genes, alleles) through some genetic interaction (e.g. epistasis)) I don't think that is appropriate for protein-protein interactions. It's probably fine for gene-gene interactions.

Maybe we could generate two graphs, one with the inverse relations where applicable and another without, to assess how much it could mess with random walk-based algorithms? I do suspect it may affect the node2vec results.

The rest looks fine to me (BTW, I like the new diagram!).

callahantiff commented 4 years ago

Yup, that is the reason I chose molecularly interacts with (binding). Looking at the definition of that other relation (An interaction that holds between two genetic entities (genes, alleles) through some genetic interaction (e.g. epistasis)) I don't think that is appropriate for protein-protein interactions. It's probably fine for gene-gene interactions.

OK, great. I also agree about the protein-protein interactions. Maybe we do this:

Maybe we could generate two graphs, one with the inverse relations where applicable and another without, to assess how much it could mess with random walk-based algorithms? I do suspect it may affect the node2vec results.

Yep, that's what Bill and I were thinking too :D.

The rest looks fine to me (BTW, I like the new diagram!).

Great, thanks for your feedback!

ignaciot commented 4 years ago

Thanks, great! I think molecularly interacts with is fine for protein-protein interactions, as that interaction implies physical binding.

ignaciot commented 4 years ago

And for chemical-gene is probably better to leave it as the more generic interacts with, as you suggested. Because there are many possible ways for the chemical to affect expression (which is what we imply by this interaction).

LEHunter commented 4 years ago

I suggest getting Mike to weigh in on these. I would like to be consistent with what he is doing with CRAFT for relations.

On Nov 26, 2019, at 3:26 PM, Tiffany J. Callahan notifications@github.com<mailto:notifications@github.com> wrote:

Yup, that is the reason I chose molecularly interacts with (binding). Looking at the definition of that other relation (An interaction that holds between two genetic entities (genes, alleles) through some genetic interaction (e.g. epistasis)) I don't think that is appropriate for protein-protein interactions. It's probably fine for gene-gene interactions.

OK, great. I also agree about the protein-protein interactions. Maybe we do this:

Maybe we could generate two graphs, one with the inverse relations where applicable and another without, to assess how much it could mess with random walk-based algorithms? I do suspect it may affect the node2vec results.

Yep, that's what Bill and I were thinking too :D.

The rest looks fine to me (BTW, I like the new diagram!).

Great, thanks for your feedback!

β€” You are receiving this because you were mentioned. Reply to this email directly, view it on GitHubhttps://github.com/callahantiff/PheKnowLator/issues/17?email_source=notifications&email_token=AACWZKP26NURHFGKTVCT3V3QVWPANA5CNFSM4JBOGE32YY3PNVWWK3TUL52HS4DFVREXG43VMVBW63LNMVXHJKTDN5WW2ZLOORPWSZGOEFHUT5A#issuecomment-558844404, or unsubscribehttps://github.com/notifications/unsubscribe-auth/AACWZKOLYRZKK47H3G3ZB5DQVWPANANCNFSM4JBOGE3Q.

LEHunter commented 4 years ago

On Nov 26, 2019, at 12:38 PM, Tiffany J. Callahan notifications@github.com<mailto:notifications@github.com> wrote:

  1. @LEHunterhttps://github.com/LEHunter - @bill-baumgartnerhttps://github.com/bill-baumgartner and I were talking about the possibility of adding the inverse properties. What are your thoughts on this? Do you think it would have negative ramifications for things like random walk?

Inverse relations are a good idea. You can try random walk with and without them to see if it’s having any impact. Maybe also approaches like prohibiting the walk from traversing an edge twice.

callahantiff commented 4 years ago

I suggest getting Mike to weigh in on these. I would like to be consistent with what he is doing with CRAFT for relations.

OK, I will reach out to Mike. Thanks @LEHunter!

callahantiff commented 4 years ago

@LEHunter - I'd like to substitute the following BFO terms for the proposed RO terms, do you agree?:

LEHunter commented 4 years ago

Seems reasonable to me, but please do check with Mike. It’s important to be consistent with CRAFT. And Mike has thought a lot about this stuff

L

On Nov 26, 2019, at 5:53 PM, Tiffany J. Callahan notifications@github.com wrote:

ο»Ώ

@LEHunterhttps://github.com/LEHunter - I'd like to substitute the following BFO terms for the proposed RO terms, do you agree?:

β€” You are receiving this because you were mentioned. Reply to this email directly, view it on GitHubhttps://github.com/callahantiff/PheKnowLator/issues/17?email_source=notifications&email_token=AACWZKNGQ66QLKK6HBM4MCDQVXAI3A5CNFSM4JBOGE32YY3PNVWWK3TUL52HS4DFVREXG43VMVBW63LNMVXHJKTDN5WW2ZLOORPWSZGOEFH5K2I#issuecomment-558880105, or unsubscribehttps://github.com/notifications/unsubscribe-auth/AACWZKPLUDL7DURSSB4S7XTQVXAI3ANCNFSM4JBOGE3Q.

callahantiff commented 4 years ago

Seems reasonable to me, but please do check with Mike. It’s important to be consistent with CRAFT. And Mike has thought a lot about this stuff L

Sounds good, I will follow-up with him. Thanks!

callahantiff commented 4 years ago

UPDATE: Mike has been emailed to ask about the BFO-RO and interaction triples. In the meantime, I am going to move forward with the representation shown below. Will also create a Bada-version πŸ˜‰, once I hear back from him.

Screen Shot 2019-11-29 at 13 08 01

NOTE. For space reasons, I am not showing all edges with labels, but am suggesting there are inverse edges via the inclusion of a dotted line.

bill-baumgartner commented 4 years ago
  1. @bill-baumgartner - I kept the edge causally influences. I was unable to find anything in the RO for options like alters or has variant.

Turns out the relation I was thinking of is in the Sequence Ontology and not the RO: https://www.ebi.ac.uk/ols/ontologies/so/properties?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2Fso%23variant_of

callahantiff commented 4 years ago
  1. @bill-baumgartner - I kept the edge causally influences. I was unable to find anything in the RO for options like alters or has variant.

Turns out the relation I was thinking of is in the Sequence Ontology and not the RO: https://www.ebi.ac.uk/ols/ontologies/so/properties?iri=http%3A%2F%2Fpurl.obolibrary.org%2Fobo%2Fso%23variant_of

Thanks for letting me know! In that case, unless you are opposed, I will keep causally influences.

callahantiff commented 4 years ago

@ignaciot - would mind telling me how you found these?

ignaciot commented 4 years ago

protein-protein

These came from Uniprot, and they are sourced from the IntAct database monthly (so it would be a good idea to keep those from STRING as well).

protein-cofactor/catalyst (ChEBI) protein-complex (reactome) chemical (ChEBI)-complex complex (reactome)-complex (reactome) protein-pathway (reactome) protein-reaction (reactome)

All of those came from Reactome, where they specified the participants (from Uniprot or ChEBI) to pathways, complexes and reactions.

callahantiff commented 4 years ago

protein-protein

These came from Uniprot, and they are sourced from the IntAct database monthly (so it would be a good idea to keep those from STRING as well).

Thanks! Update on protein-protein interactions. It looks like we will only need STRING as they already cover the data in IntAct (see screenshot below) πŸŽ‰

Screen Shot 2019-12-02 at 21 30 58

protein-cofactor/catalyst (ChEBI) protein-complex (reactome) chemical (ChEBI)-complex complex (reactome)-complex (reactome) protein-pathway (reactome) protein-reaction (reactome)

All of those came from Reactome, where they specified the participants (from Uniprot or ChEBI) to pathways, complexes and reactions.

Perfect! I will update the file parsers.

ignaciot commented 4 years ago

Awesome! One less thing to worry about, then.

callahantiff commented 4 years ago

@ignaciot - to build the gene - has_gene_product - protein triples, we need to identify all human protein coding genes and their gene products.

To get this, I'm using the human proteome (reviewed Swiss-Prot version) from Uniprot (here). Sound OK to you?

ignaciot commented 4 years ago

Yup! That makes sense.

callahantiff commented 4 years ago

@ignaciot - can you confirm that you agree with how I am building the protein-protein and protein-complex edges from the ComplexParticipantsPubMedIdentifiers_human.txt file:


FILE DATA

File Columns: [0] identifier; [1] name; [2] participants; [3] participatingComplex; [4] pubMedIdentifiers

Example File Output: NOTE. '|" substituted for ";" to build table in example below

identifier name participants participatingComplex pubMedIdentifiers
R-HSA-1006173 "CFH:Host cell surface [plasma membrane]" uniprot:P08603;chebi:24505;chebi:28879 R-ALL-1006146 762425;16192651
R-HSA-1008206 "NF-E2:Promoter region of beta-globin [nucleoplasm]" uniprot:Q16621;uniprot:Q9ULX9;uniprot:O15525;uniprot:O60675 R-HSA-1008229 8816476


BUILDING EDGES

Protein-Complex:

Example from file (from table above):

complex protein
R-HSA-1006173 uniprot:P08603
R-HSA-1008206 uniprot:Q16621
uniprot:Q9ULX9
uniprot:O15525
uniprot:O6067

Complex-Complex:

Example from file (from table above):

complex complex
R-HSA-1006173 R-ALL-1006146
R-HSA-1008206 R-HSA-1008229
ignaciot commented 4 years ago

These all look correct!

callahantiff commented 4 years ago

Good news, the draft of the sources of data for the edges and documentation of sources are complete. The edge counts will be updated and the files listed on the release page will be added as the KG is built.

@ignaciot - would you mind taking a gander at the following pages and let me know if anything seems incorrect?

What's Left before KG Build:

Once I confirm a few last details with @bill-baumgartner tomorrow (who was super helpful today, thanks Bill!), I will begin the build!

ignaciot commented 4 years ago

This looks AWESOME!! I'm glad those Uniprot/Reactome triples resulted to be useful, can't wait to play with the built graph. I went through all of the above and didn't see any errors. Thanks for adding those inverse relations, too!

Happy to help check the items above that need testing. Maybe we could think of a set of unit tests to write for each build, too (can wait until the next subrelease).

callahantiff commented 4 years ago

This looks AWESOME!! I'm glad those Uniprot/Reactome triples resulted to be useful, can't wait to play with the built graph. I went through all of the above and didn't see any errors. Thanks for adding those inverse relations, too!

Happy to help check the items above that need testing. Maybe we could think of a set of unit tests to write for each build, too (can wait until the next subrelease).

Thanks so much for your help @ignaciot! I think writing tests is a great idea. I also think it would be great if we added continuous integration. Perhaps we can chat more about this on Monday?

callahantiff commented 4 years ago

@bill-baumgartner and @ignaciot - the human version of the PRO is finally done! πŸŽ‰

Things to keep in mind:

If you'd like to use it, you can download the closed and unclosed versions here:


@LEHunter and @bill-baumgartner - should we offer this version and/or the script used to create it to the ProConsortium?


πŸ“’Now that the core ontologies are good to go, I will begin building KG. Updates to follow!

ignaciot commented 4 years ago

@ignaciot - I found a way to do this such that it includes all of the things we discussed needed to be included (e.g. PR_000000019) :-)

Awesome!! This is really cool.

I take it the pr:lacks_part and owl:disjointWith had to be kept to keep it a single connected component? (my only concert would be the incorrect assumption of a relation when creating node embeddings)

callahantiff commented 4 years ago

@ignaciot - I found a way to do this such that it includes all of the things we discussed needed to be included (e.g. PR_000000019) :-)

Awesome!! This is really cool.

I take it the pr:lacks_part and owl:disjointWith had to be kept to keep it a single connected component? (my only concert would be the incorrect assumption of a relation when creating node embeddings)

Thanks! πŸ˜„ After reading a bunch of articles, I chose to leave both types in for now as this is the way to create the most "correct"/authentic version of the human PRO. There is a way to keep 1 single component with removing each type. The owl:disjointWith will continued to be removed prior to closing the graph (we have been doing that since the first release (the reasoners ignore this axiom anyways) so they should not give you trouble with the embeddings. I believe the pr:lacks_part axioms should be OK. I read some of Hohendorf's papers about the pr:lacks_part axioms and given how they are constructed in PRO and CL, we should be fine. The real problem with including these are when they are constructed in the way PATO uses them. Either way, I'm happy to discuss this again once the KG is built πŸ˜„

ignaciot commented 4 years ago

Oh, absolutely, I don't think this is a reason to halt building the next KG version! I'm excited to try this out once it's built!

callahantiff commented 4 years ago

Oh, absolutely, I don't think this is a reason to halt building the next KG version! I'm excited to try this out once it's built!

Awesome! I’ll let you know when it’s ready for you!

callahantiff commented 4 years ago

Final KR for V2.0 builds are shown below.


Instance-Based Construction
PheKnowLator_v2 0 0_KnowledgeRepresentation_Instance


Subclass-Based Construction PheKnowLator_v2 0 0_KnowledgeRepresentation_subclass


Closing this issue.