Table 1.

Data sources integrated for constructing iBKH

Source	Description	Entity		Relation		URL	License
		Types	Number	Types	Number
Bgee31	A database for retrieval and comparison of gene expression patterns across multiple animal species.	Anatomy, Gene	60,072	Anatomy-Express Present-Gene, Anatomy-Express Absent-Gene	11,731,369	https://bgee.org/	https://creativecommons.org/publicdomain/zero/1.0/
BRENDA Tissue Ontology27	A tissue-specific ontology.	Tissue (Anatomy)	6,478	–	–	https://www.brenda-enzymes.org/index.php	https://creativecommons.org/licenses/by/4.0/
Cell Ontology28	A structured controlled vocabulary for cell types in animals.	Cells (Anatomy)	2,200	–	–	http://obofoundry.org/ontology/cl.html	https://creativecommons.org/licenses/by/4.0/
Comparative Toxicogenomics Database (CTD)32	A knowledge base that relates toxicological information for chemicals, genes, phenotypes, and diseases, as well as literature-based and manually curated interactions	Disease, Gene, Drug, Pathway	73,922	Chemical-Gene, Chemical-Disease, Chemical-Pathway, Gene-Disease, Gene-Pathway, Disease-Pathway	38,344,568	http://ctdbase.org/	Confirmed via e-mail.
ChEMBL42	A manually curated database of bioactive molecules with drug-like properties.	Molecular	1,940,733	–	–	https://www.ebi.ac.uk/chembl/	https://creativecommons.org/licenses/by-sa/3.0/
Chemical Entities of Biological Interest (ChEBI)43	A freely available dictionary of molecular entities focused on ‘small’ chemical compounds	Molecular	155,342	–	–	https://www.ebi.ac.uk/chebi/init.do	https://creativecommons.org/licenses/by/4.0/
Drug Repurposing Knowledge Graph (DRKG)39	A biological knowledge graph.	Anatomy, Pathway, Compound (Drug), Disease, Gene, Molecular function, Pathway, Pharmacologic class, Side effect, Symptom	97,238	Gene-Gene, Compound-Gene, Disease-Gene, Atc-Compound, Compound-Compound, Compound-Disease, Gene-Tax, Biological process-Gene, Disease-Symptom, Anatomy-Disease, Disease-Disease, Anatomy-Gene, Gene-Molecular function, Compound-Pharmacologic class, Cellular component-Gene, Gene-Pathway, Compound-Side effect	5,874,261	https://github.com/gnn4dr/DRKG	https://www.apache.org/licenses/LICENSE-2.0
Disease Ontology29	Standardized ontology for human disease.	Disease	10,648	–	–	https://disease-ontology.org/	https://creativecommons.org/publicdomain/zero/1.0/
DrugBank33	A web-enabled database containing comprehensive molecular information about drugs, their mechanisms, their interactions, and their targets.	Drug	15,128	Drug-Target, Drug-Enzyme, Drug-Carrier, Drug-Transporter	28,014	https://go.drugbank.com/	http://creativecommons.org/licenses/by-nc/4.0/
Hetionet4	A biomedical knowledge graph for drug repurposing.	Anatomy, Biological process, Cellular component, Compound (Drug), Disease, Gene, Molecular function, Pathway, Pharmacologic class, Side effect, Symptom	47,031	Anatomy–downregulates–Gene, Anatomy–expresses–Gene, Anatomy–upregulates–Gene, Compound–binds–Gene, Compound–causes–Side Effect, Compound–downregulates–Gene, Compound–palliates–Disease, Compound–resembles–Compound, Compound–treats–Disease, Compound–upregulates–Gene, Disease-associates-Gene, Disease–downregulates–Gene, Disease–localizes–Anatomy, Disease–presents–Symptom, Disease–resembles–Disease, Disease–upregulates–Gene, Gene–covaries–Gene, Gene–interacts–Gene, Gene–participates–Biological Process, Gene–participates–Cellular Component, Gene–participates–Molecular Function, Gene–participates–Pathway, Gene–regulates–Gene, Pharmacologic Class–includes–Compound	2,250,197	https://github.com/hetio/hetionet	https://creativecommons.org/publicdomain/zero/1.0/
HUGO Gene Nomenclature Committee (HGNC)41	The resource for approved human gene nomenclature	Gene	41,439	–	–	https://www.genenames.org/	No restriction
Integrated Dietary Supplement Knowledge Base (iDISK)40	Our curated knowledge graph that covers a variety of dietary supplements, including vitamins, herbs, minerals, etc.	Dietary Supplement Ingredient, Dietary Supplement Product, Disease, Drug, Anatomy, Symptom, Therapeutic Class	144,536	DSI-Anatomy, DSI-Symptom, DSI-Disease, DSI-Drug, DSI-DSP, DSI-TC	705,075	https://conservancy.umn.edu/handle/11299/204783	Our copyright. https://creativecommons.org/licenses/by-sa/3.0/us/
Kyoto Encyclopedia of Genes and Genomes (KEGG)34	A biomedical knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information.	Drug, Disease, Gene, Pathway	42,181	Drug-Gene, Disease-Gene, Gene-Pathway, Drug-Disease, Drug-Pathway, Disease-Pathway	65,505	https://www.kegg.jp/	KEGG forbids data redistribution. The deployed version of iBKH excluded KEGG data.
Pharmacogenetics Knowledge Base (PharmGKB)35	A biomedical knowledge base containing genomic, phenotype and clinical information collected from ongoing pharmacogenetic studies.	Genes, Variant, Drug, Phenotype	43,112	Disease-Gene, Drug/Chemical -Gene, Gene-Gene, Gene-Variant, Disease-Variant, Drug/Chemical-Variant	61,616	https://www.pharmgkb.org/	https://creativecommons.org/licenses/by-sa/4.0/
Reactome36	A knowledge base of molecular details of signal transduction, transport, DNA replication, metabolism, and other cellular processes.	Genes, Pathways (H. sapiens)	13,589	Gene-Pathway	13,732	https://reactome.org/	https://creativecommons.org/licenses/by/4.0/
Side effect resource (SIDER)37	A data resource of public information on drug side effects.	Drugs, Side effects	5,681	Drug-Side effect	163,206	http://sideeffects.embl.de/	https://creativecommons.org/licenses/by-nc-sa/4.0/
TISSUE38	A public resource that integrates evidence on tissue expression from manually curated literature, proteomics and transcriptomics screens, and automatic text mining.	Genes, Tissues	26,260	Tissue-Express-Gene	6,788,697	https://tissues.jensenlab.org/	https://creativecommons.org/licenses/by/4.0/
Uberon30	A cross-species anatomy ontology.	Anatomy	14,944	–	–	https://www.ebi.ac.uk/ols/ontologies/uberon	http://creativecommons.org/licenses/by/3.0/