{ "version": "https://jsonfeed.org/version/1.1", "title": "chem-bla-ics", "description": "Chemblaics (pronounced chem-bla-ics) is the science that uses open science and computers to solve problems in chemistry, biochemistry and related fields.", "home_page_url": "https://chem-bla-ics.linkedchemistry.info/", "feed_url": "https://chem-bla-ics.linkedchemistry.info/2025/01/05/sr24-results.json", "icon": "https://chem-bla-ics.linkedchemistry.info/assets/images/chem-bla-ics_logo.png", "language": "en", "authors": [ { "name": "Egon Willighagen", "url": "https://orcid.org/0000-0001-7542-0286", "_orcid": "0000-0001-7542-0286" } ], "items": [ { "id": "https://doi.org/10.59350/fjbv7-53d20", "url": "https://chem-bla-ics.linkedchemistry.info/2025/01/05/sr24-results.html", "title": "Serious Request: the results", "content_html": "

The last week before the winter break Serious Request took place.\nWe started an action around WikiPathways and\nwe collected 877 euro for the MetaKids Foundation. In total there were 2612\nactions, many of which brought in a lot more. We ended up in position 928.

\n\n

But the money was only one part of our “donation” of the MetaKids goal to make 35 percent point more inherited metabolic\ndisorders treatable (which they currently are not), and to address the number one cause of death among Dutch kids.\nBecause our action focussed on getting more biology relevant to metabolic diseases into WikiPathays. For this we set\nup a WikiPathways SR24 community page, along with a curation page\nshowing the results of automated curation alerts. Actually, in preparation of the Action, I updated that code\nbase to no longer have two states (succeeded, failed), but four states, depending on the percentage of tests failing\nfor that pathway. This has also been roled out to the main WikiPathways website.

\n\n

In the weekend before our action, I wanted to test my PathVisio and had a go at a pathway drawing\nfrom a book of which most pathways had already been digitized (see doi:10.1007/978-3-030-67727-5_73),\nbut not this one. This resulted in a first pathway (wikipathways:WP5504),\nwhich was later that week greatly extended by Denise.\nI also ported the table of chapters from this book to the new WikiPathways community page for the book.

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A list of genes

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From Marek Noga from our university medical center\nI received a pointer to a nice paper with a long list of diseases and matching genes (doi:10.1002/jimd.12348)\nwhich provided a great starting point. I started out by making the data from the supplementary files more FAIR\nby converting the data into RDF.

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With SPARQL I compared the genes (via their HGNC symbols) with the content of WikiPathways:

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PREFIX wp:      <http://vocabularies.wikipathways.org/wp#>\nPREFIX dc:      <http://purl.org/dc/elements/1.1/>\n\nSELECT ?gene ?omim ?geneLabel WHERE {\n  ?gene a wp:GeneProduct ;\n    rdfs:label ?geneLabel .\n  OPTIONAL {\n    ?gene rdfs:seeAlso ?omimIRI .\n    ?omimIRI dc:identifier ?omim .\n    FILTER (contains(str(?omimIRI), \"omim:\"))\n  }\n  ?gene wp:bdbHgncSymbol ?hgnc .\n  OPTIONAL {\n    SERVICE <https://sparql.wikipathways.org/sparql> {\n      ?wpGene wp:bdbHgncSymbol ?hgnc .\n    }\n  }\n  FILTER (!BOUND(?wpGene))\n  FILTER (CONTAINS(?geneLabel, \" \"))\n}\n
\n\n

This resulted in a spreadsheet with more than 300 genes not in WikiPathways.\nAn analysis by Karen Rothfels and Lisa Matthews showed that the number of genes not found in Reactome\nis only 129. Indeed, later analyses showed that Reactome has a few very relevant pathways missing in\nWikiPathways.

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New biological pathways

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To figure out, it turns out the Pathway Figure OCR (doi:10.1186/s13059-020-02181-2)\nand NDEX (doi:10.1093/bioinformatics/btad118) tools\nare very useful here. They both allow passing a list of genes and return results (sets, pathways, models) relevant to\nthat list. NDEX includes the sets from Pathway Figure OCR, and those sets are a set of genes linked to single\njournal article which included a pathway diagram. I used this on the list of 371 genes not in WikiPathways and the list\nof 129 genes not in Reactome, and identified five articles. It actually turns out that two\nbasically described the same biology and both are captured in the same new pathway\n(wikipathways:WP5505). This pathway includes a good number\nof PIG genes, handling the very specific metabolic conversion of a metabolite.

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Complex chemistry

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That metabolite is complex and databases do not seem to have the structure yet, so I set out\ngenerating a SMILES:

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\"\"

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I reported the final SMILES, but I am not happy with it yet, and actually spotted an error already:

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N[Prot]C(=O)NCCOP(=O)([O-])OC[C@@H]1[C@@H](O)[C@H]([R11])[C@H]([R10])[C@@H](O1)O[C@H]1[C@@H]([R8])[C@H](O)[C@@H](C[R9])O[C@H]1OC[C@@H]1[C@@H]([R7])[C@H]([R6])[C@H]([R5])[C@@H](O1)OC[C@@H]1[C@@H](O[M3])[C@H](O)[C@@H](N)[C@H](O1)O[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H]([R3])[C@H]1OP(=O)([O-])OC[C@H]([R1])C[R2]\n
\n\n

So, for completeness and as backup, here are the fragment SMILES that you can copy/paste into CDK Depict:

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N[Prot]C(=O)NCCOP(=O)([O-])OC[C@@H]1[C@@H](O)[C@H]([R11])[C@H]([R10])[C@@H](O1)O[C@H]1[C@@H]([R8])[C@H](O)[C@@H](C[R9])O[C@H]1OC[C@@H]1[C@@H]([R7])[C@H]([R6])[C@H]([R5])[C@@H](O1)OC[C@@H]1[C@@H](O[M3])[C@H](O)[C@@H](N)[C@H](O1)O[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H]([R3])[C@H]1OP(=O)([O-])OC[C@H]([R1])C[R2]\nN[Prot]C(=O)NCCOP(=O)([O-])O protein-linked ethanolamine phosphate (E0)\n[E0]OC[C@@H]1[C@@H](O)[C@H]([R11])[C@H]([R10])[C@@H](O1)O[M2] Manα1-2 (M1)\n[M1]O[C@H]1[C@@H]([R8])[C@H](O)[C@@H](C[R9])O[C@H]1O[M3] Manα1-6 (M2)\n[M2]OC[C@@H]1[C@@H]([R7])[C@H]([R6])[C@H]([R5])[C@@H](O1)O[G4] Manα1-4 (M3)\n[R4]C[C@@H]1[C@@H](O[M3])[C@H](O)[C@@H](N)[C@H](O1)O[S5] GlCNα1-6 (G4)\n[G4]O[C@@H]1[C@@H](O)[C@H](O)[C@@H](O)[C@@H]([R3])[C@H]1OP(=O)([O-])OC[C@H]([R1])C[R2] phosphatidylinositol (S5)\n
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The hackathon day

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On Thursday we had a hackathon day at our Translational Genomics department\n(UNS60 building). One of the Action organizers was still travelling back from Germany, but otherwise Tina, Denise, Daan, me, and Marek worked\non Thursday on various things. Tina worked on WP5505, Daan created his first pathways (wikipathways:WP5507),\nand so did Marek (wikipathways:WP5506).

\n\n

We now have 36 pathways on the community page:

\n\n

\"\"

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After that hackathon, and to wrap up things, I finalized the updated to the curation page, making the output\nlook better (more curation tests now output Markdown) and failing tests now almost all have an explanation page\nshowing how the affected pathway can be improved (to address the issue).

\n\n

Somewhere next week, the results of the pathways will be available from the WikiPathways SPARQL endpoint\nand I can then calculate new numbers. The number of genes not in WikiPathways should be lower.

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Finally, perhaps, there are some very specific results, but also we have created a nice todo list:

\n\n\n\n

And there are also still a few issues open:

\n\n\n\n

That bug actually has significant impact on downstream analyses, I guestimate.

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References

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Ferreira, C. R., Rahman, S., Keller, M., & Zschocke, J. (2021). An international classification of inherited metabolic disorders (                    <scp>ICIMD</scp>                    ). Journal of Inherited Metabolic Disease, 44(1), 164–177. https://doi.org/10.1002/jimd.12348 CrossRef Scholia
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Hanspers, K., Riutta, A., Summer-Kutmon, M., & Pico, A. R. (2020). Pathway information extracted from 25 years of pathway figures. Genome Biology, 21(1). https://doi.org/10.1186/s13059-020-02181-2 CrossRef Scholia
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Pillich, R. T., Chen, J., Churas, C., Fong, D., Gyori, B. M., Ideker, T., Karis, K., Liu, S. N., Ono, K., Pico, A., & Pratt, D. (2023). NDEx IQuery: a multi-method network gene set analysis leveraging the Network Data Exchange. Bioinformatics, 39(3). https://doi.org/10.1093/bioinformatics/btad118 CrossRef Scholia
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Slenter, D. N., Kutmon, M., & Willighagen, E. L. (2022). WikiPathways: Integrating Pathway Knowledge with Clinical Data. In Physician’s Guide to the Diagnosis, Treatment, and Follow-Up of Inherited Metabolic Diseases (pp. 1457–1466). Springer International Publishing. https://doi.org/10.1007/978-3-030-67727-5_73 CrossRef Scholia
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", "summary": "The last week before the winter break Serious Request took place. We started an action around WikiPathways and we collected 877 euro for the MetaKids Foundation. In total there were 2612 actions, many of which brought in a lot more. We ended up in position 928.", "image": "https://chem-bla-ics.linkedchemistry.info/assets/images/b0fbb7ea135318b9.png", "date_published": "2025-01-05T00:00:00+00:00", "date_modified": "2025-01-17T00:00:00+00:00", "tags": ["sr24"], "_references": [ { "url": "https://doi.org/10.1002/jimd.12348", "doi": "10.1002/jimd.12348" } , { "url": "https://doi.org/10.1007/978-3-030-67727-5_73", "doi": "10.1007/978-3-030-67727-5_73" } , { "url": "https://doi.org/10.1186/s13059-020-02181-2", "doi": "10.1186/s13059-020-02181-2" } , { "url": "https://doi.org/10.1093/bioinformatics/btad118", "doi": "10.1093/bioinformatics/btad118" } ], "authors": [ { "name": "Egon Willighagen", "url": "https://orcid.org/0000-0001-7542-0286" } ] } ] }