KG construction

Intro

We use CURIEs identifiers https://en.wikipedia.org/wiki/CURIE. They can be resolved in https://identifiers.org/ - The Identifiers.org Resolution Service provides consistent access to life science data using Compact Identifiers. (TODO: alternative https://bioregistry.io/)

Glossary

• id - Primary reference

• labels - type of entity

• xref - Secondary refs for linking etc

• tui - UMLS semantic type codes

• cui - UMLS codes

• umls_sty - UMLS semantic type literal

Ontologies

Ontology is used to classify entities. In BioMedical domains there are long list of well-known and curated ontologies. We select one ontology per entity type as primary ontology for these entity.

• ATC - ontology for chemical compounds. The Anatomical Therapeutic Chemical (ATC) Classification System is used for the classification of active ingredients of drugs according to the organ or system on which they act and their therapeutic, pharmacological and chemical properties. It is controlled by the World Health Organization Collaborating Centre for Drug Statistics Methodology (WHOCC)

  • id ATC:ID

  • labels (type) - ATC_term

  • name

  • tui

  • cui

  • umls_sty

  • data https://bioportal.bioontology.org/ontologies/ATC

• MeSH - mixed ontology of bio-medical terms, chemical compounds, diseases etc.

  • id - MESH:ID

  • labels - MESH_term

  • name

  • tui

  • cui

  • umls_sty

  • data https://bioportal.bioontology.org/ontologies/MESH

• DOID - Disease. The Disease Ontology has been developed as a standardized ontology for human disease with the purpose of providing the biomedical community with consistent, reusable and sustainable descriptions of human disease terms, phenotype characteristics and related medical vocabulary disease concepts through collaborative efforts of biomedical researchers, coordinated by the University of Maryland School of Medicine, Institute for Genome Sciences. The Disease Ontology semantically integrates disease and medical vocabularies through extensive cross mapping of DO terms to MeSH, ICD, NCI's thesaurus, SNOMED and OMIM.

  • id DOID:ID - https://disease-ontology.org/

  • xref

  • name

  • data - CKG

Entities

List of datasets containing entity instances (metadata) and information on relationships, interactions etc., between entities.

• Companies - FDA's companies

  • id - DUNS:ID https://www.fdahelp.us/fda-establishment-registration-ndc-labeler-code-number.html

  • xref - ?

  • name

  • data

    • https://www.fda.gov/drugs/drug-approvals-and-databases/drug-establishments-current-registration-site

    • https://www.accessdata.fda.gov/scripts/cder/wdd3plreporting/index.cfm

    • https://www.fda.gov/drugs/drug-supply-chain-security-act-dscsa/annual-reporting-prescription-drug-wholesale-distributors-and-third-party-logistics-providers

      • https://www.fda.gov/about-fda/ethics/listing-significantly-regulated-organizations-sro

      • https://www.accessdata.fda.gov/scripts/sda/sdNavigation.cfm?sd=srolist&displayAll=false&page=1

      • https://www.fda.gov/medical-devices/device-registration-and-listing/establishment-registration-and-medical-device-listing-files-download

• Drug_product(labels)

  • id NDC:ID - National Drug Code (NDC) which serves as the FDA's identifier for drugs

    • https://www.fda.gov/drugs/drug-approvals-and-databases/approved-drug-products-therapeutic-equivalence-evaluations-orange-book

    • https://www.fda.gov/drugs/drug-approvals-and-databases/national-drug-code-directory

  • xref

  • name

  • data - see Companies entities

• Chemical compound

  • id PubChem.Compound:ID - PubChem ID - https://pubchem.ncbi.nlm.nih.gov/

  • xref UNII ID https://fdasis.nlm.nih.gov/srs/jsp/srs/uniiListDownload.jsp

  • name

  • data

    • rxnorm_mapping https://dailymed.nlm.nih.gov/dailymed/spl-resources-all-mapping-files.cfm

• Genes

  • id - HGNC https://www.genenames.org/

  • xref

  • name

  • data - CKG

• Proteins

  • id - UniProt https://www.uniprot.org/

  • xref

  • name

  • data - CKG

• Med Devices

  • id - 510(K) Number ID

  • xref

  • name

  • data

• ClinicalTrials

  • id clinicaltrials:ID (https://registry.identifiers.org/registry/clinicaltrials)

  • name

  • data

    • https://aact.ctti-clinicaltrials.org/ - Database (Postgres)

    • https://aact.ctti-clinicaltrials.org/schema - Schema

• Disease

  • id DOID:ID - https://disease-ontology.org/

  • xref

  • name

  • data - CKG

• Vaccines

  • id Vaccines are part of Drug_product

  • xref

  • name

  • data

• Patents

  • data https://www.surechembl.org/search/ - Patents annotated by chemical compounds

Relationships

Output format

Output format is presented as table where specifically defined columns names and name of table help to process data in connected graph. All processed tables could be pushed to graph construction script and KG will be built automatically.

::: centering {#fig:Example-of-table} :::

• Drug_product.csv - Table name is exact Entity type

• ID,Product_type,Application_number - simple columns names - metadata for node

• REL:has_ingredient - column starts with REL: is for outgoing relations with name of relation after ":" It contains list of IDs of entities to be linked with entity in registry (current line) (n)-[has_ingredient]->(m)

• LER:manufactures - column starts with LER: is for incoming relations with name of relation after ":" It contains list of IDs of entities to be linked with entity in registry (current line) (n)<-[manufactures]-(m)

Example of table is presented in Fig. 1{reference-type="ref" reference="fig:Example-of-table"}

Final Knowledge Graph is presented on Fig. 2{reference-type="ref" reference="fig:Graph"}

::: centering :::

Data Review

Ontology/Semantic type (probable)

• https://lhncbc.nlm.nih.gov/semanticnetwork/

• https://bioportal.bioontology.org/

Genes

• https://www.ncbi.nlm.nih.gov/gene?cmd=Retrieve&dopt

• https://www.ensembl.org/index.html

Proteins

• https://www.uniprot.org/

Compounds

Drugs

• https://pubchemdocs.ncbi.nlm.nih.gov/statistics

• https://bioportal.bioontology.org/ontologies/ATC/

• https://www.ebi.ac.uk/chembl/

• FDA resources

  • https://www.fda.gov/drugs

  • https://fda.report/

  • https://open.fda.gov/

  • https://dailymed.nlm.nih.gov/dailymed/index.cfm

  • https://www.accessdata.fda.gov/scripts/cder/daf/ - Approved drugs

  • https://www.altexsoft.com/blog/drug-data-openfda-dailymed-rxnorm-goodrx/ list of APIs to Drug databases

• https://drugcentral.org/

• EMA

  • https://www.ema.europa.eu/en

  • https://ec.europa.eu/health/documents/community-register/html/reg_hum_atc.htm - Centralised medicinal products for human use by ATC code

• https://www.kegg.jp/kegg/drug/ - KEGG DRUG is a comprehensive drug information resource for approved drugs in Japan, USA and Europe, unified based on the chemical structure and/or the chemical component of active ingredients.

Biologics

Vaccines, blood and tissue products, and biotechnology. New biologics are required to go through a premarket approval process called a Biologics License Application (BLA), similar to that for drugs.

• https://www.fda.gov/vaccines-blood-biologics

Product

• https://go.drugbank.com/

• https://www.accessdata.fda.gov/scripts/cder/daf/ - Approved drugs

Medical Devices

• https://www.fda.gov/medical-devices

• https://bioportal.bioontology.org/ontologies/SNOMEDCT

• https://bioportal.bioontology.org/ontologies/MESH

Food

• https://www.fda.gov/food - Food and dietary supplements

Diseases

• https://www.ebi.ac.uk/efo/

• https://www.ebi.ac.uk/ols/ontologies/mondo

• https://www.ebi.ac.uk/ols/ontologies/doid

• https://www.nlm.nih.gov/mesh/meshhome.html

• https://icd.who.int/en

• https://www.ebi.ac.uk/ols/ontologies/ncit

Pathways

• https://reactome.org/what-is-reactome

Clinical Trials

• NIH (clinicaltrials.gov, data dump - https://aact.ctti-clinicaltrials.org/)

• EU Clinical Trials Register (clinicaltrialsregister.eu) (https://eudract.ema.europa.eu/)

• WHO International (https://www.who.int/clinical-trials-registry-platform)

Patents

• https://www.surechembl.org/

• http://www.almaden.ibm.com/

• https://patentscope.wipo.int/

Intearactions

• Drug --> Drug: https://mor.nlm.nih.gov/RxNav/

• Chemicals -> Proteins http://stitch.embl.de/

Combo

• https://www.opentargets.org/

• https://pharos.nih.gov/about

APIs

• https://biothings.io/

• http://mychem.info/

Knowledge Graphs

• https://github.com/callahantiff/PheKnowLator - https://youtu.be/uNAFd6GgwGE

• https://github.com/gnn4dr/DRKG

• https://github.com/MannLabs/CKG

• https://het.io/

• https://github.com/Knowledge-Graph-Hub/kg-covid-19

• https://github.com/dsi-bdi/biokg

• https://monarchinitiative.org/

• https://github.com/MindRank-Biotech/PharmKG

• https://github.com/OpenBioLink/OpenBioLink

• https://data.mendeley.com/datasets/mrcf7f4tc2/1

Notes

L-.1667em.25emY-.125emX LaTeX

Elsevier Biology KG

Entity type Quantity
Cell    4,181
Cell object 609
Cell process    14,906
Clinical parameter  5,284
Disease 22,433
Genetic Variant 157,344
Small molecule (drug)   1,057,236
Protein/gene    141,779
Complex 992
Functional class    5,485
Organ   3,857
Tissue  579
Virus   25,287
Treatment   82
Total   1,440,054