Map identifiers between databases.

SYNTAX: biobtree_map(terms="ID", chain=">>source>>target")

• Chain MUST start with ">>"

• Source MUST match input ID type

ID TYPE → SOURCE:

• ENSG* → >>ensembl

• P*/Q*/O* → >>uniprot

• CHEMBL* → >>chembl_molecule

• GO:* → >>go

• MONDO:* → >>mondo

• HP:* → >>hpo

• HGNC:* or gene symbols → >>hgnc

SOME DRUG EXPLORATION PATHS:

• chembl_molecule>>chembl_target>>uniprot (drug targets)

• pubchem>>pubchem_activity>>uniprot (bioactivity)

• gtopdb_ligand>>gtopdb_interaction>>gtopdb>>uniprot (curated pharmacology with affinity data)

• ensembl>>reactome>>chebi (pathway chemicals - when no direct targets)

• Discover more via entry xrefs + EDGES

WARNING - GO terms with high xref_count (>100):

• Don't map GO → proteins → drugs (too many results)

• Instead: search drug class for condition → verify targets this GO term

DISEASE GENE PATTERNS:

• mondo>>gencc>>hgnc (curated)

• mondo>>clinvar>>hgnc (variant-based)

• hgnc>>clingen_gene_validity (ClinGen evidence tier), >>hgnc>>clingen_dosage (haploinsufficiency), >>hgnc>>clingen_variant>>clinvar (ACMG, then dbsnp)

CANCER / CELL LINE:

• hgnc>>intogen (cancer driver gene?), >>hgnc>>civic (clinical variant interpretations)

• uniprot>>cellosaurus (cell lines for a protein/gene)

• hgnc>>depmap (CRISPR essentiality / target tractability), >>hgnc>>entrez>>depmap_dependency>>cellosaurus (which lines depend on the gene)

GENE FUNCTION / LITERATURE:

• entrez>>generif (cited one-line functional claims; >>generif>>pubmed for citations)

DISEASE → DRUG PATTERNS:

• mesh>>chembl_molecule (MeSH disease/condition → drugs with indications)

• mondo>>clinical_trials>>chembl_molecule (disease → trial drugs)

DISCOVERY APPROACH:

• Use biobtree_entry to see xrefs (what's connected)

• Use EDGES above to see where each dataset leads

• Build chains based on what connections exist for YOUR entity

RETURNS: mapped identifiers with dataset and name

EDGES (what connects to what): ensembl: uniprot, go, transcript, exon, ortholog, paralog, hgnc, entrez, refseq, bgee, gwas, gencc, antibody, scxa, civic, intogen, hpa, hpa_antibody, pharmgkb_var_annotation, chembl_mechanism, ncrna_disease, ncrna_interaction, ncrna_drug, alliance_disease, gnomad_constraint, drugcentral, panelapp_gene hgnc: ensembl, uniprot, entrez, gencc, pharmgkb_gene, msigdb, clinvar, mim, refseq, alphafold, collectri, gwas, hpo, cellphonedb, civic, intogen, cellosaurus, clingen_gene_validity, clingen_dosage, clingen_variant, depmap, hpa, pharmgkb_var_annotation, chembl_mechanism, ncrna_disease, ncrna_interaction, ncrna_drug, alliance_disease, drugcentral, panelapp_gene, gnomad_constraint, mavedb entrez: ensembl, uniprot, refseq, go, biogrid, pubchem_activity, ctd_gene_interaction, dbsnp, civic, intogen, clingen_dosage, generif, depmap, depmap_dependency, hpa, pharmgkb_var_annotation, orthologentrez, relatedentrez, neighborentrez, mgi, rgd, zfin, wormbase, xenbase, sgd, flybase, gnomad_constraint, drugcentral orthologentrez: entrez # cross-species gene orthologs (NCBI gene_orthologs). >>entrez>>orthologentrez gives ortholog genes (filter species via taxonomy); reliable from model-organism genes (human-gene side currently incomplete) relatedentrez: entrez # related genes (bidirectional): NCBI gene_group (functional gene/pseudogene/readthrough/region) + HGNC gene-family co-members neighborentrez: entrez # genomic neighbors (left/right/overlapping); edge carries distance + side, neighbor strand/position in attrs; filter to genes via [type!="biological-region"] gnomad_constraint: ensembl, entrez, hgnc, transcript # gene LoF constraint (pLI/LOEUF/oe_lof); reach via >>ensembl>>gnomad_constraint drugcentral: chembl_molecule, pubchem, uniprot, ensembl, hgnc, entrez # approved drugs -> targets/MOA + FDA/EMA/PMDA approval; reach via name/INN/InChIKey or compound (chembl_molecule/pubchem >> drugcentral) refseq: ensembl, entrez, taxonomy, ccds, uniprot, mirdb mirdb: refseq transcript: ensembl, exon, ufeature, alphamissense, civic_variant, gnomad_constraint, mavedb uniprot: ensembl, alphafold, interpro, pfam, pdb, ufeature, intact, string, string_interaction, biogrid, biogrid_interaction, chembl_target, go, reactome, rhea, swisslipids, bindingdb, antibody, pubchem_activity, cellphonedb, jaspar, signor, diamond_similarity, esm2_similarity, alphamissense, cellosaurus, hpa, chembl_mechanism, ncrna_interaction, drugcentral, mavedb alphafold: uniprot interpro: uniprot, go, interproparent, interprochild chembl_molecule: mesh, chembl_activity, chembl_target, pubchem, chebi, clinical_trials, chembl_moleculeparent, chembl_moleculechild, chembl_mechanism, ncrna_drug, faers, drugcentral # parent=anhydrous/parent form, child=salt forms chembl_activity: chembl_molecule, chembl_assay, bao chembl_assay: chembl_activity, chembl_target, chembl_document, bao chembl_target: chembl_assay, uniprot, chembl_molecule, chembl_mechanism chembl_mechanism: chembl_molecule, chembl_target, uniprot, hgnc, ensembl # curated drug mechanism-of-action (incl. RNA therapeutics): drug >> chembl_mechanism, target/gene >> chembl_mechanism pubchem: chembl_molecule, chebi, hmdb, pubchem_activity, pubmed, patent_compound, bindingdb, ctd, pharmgkb, ncrna_drug, faers, drugcentral faers: chembl_molecule, pubchem, faers_reaction # openFDA FAERS drug->adverse-event; faers (per-drug master) -> faers_reaction children (PRR), reach via drug name or compound. NOTE co-occurrence not causation faers_reaction: faers # one per (drug,reaction): report_count, prr, serious_count, outcome; most-reported first pubchem_activity: pubchem, ensembl, uniprot chebi: pubchem, rhea, intact swisslipids: uniprot, go, chebi, uberon, cl lipidmaps: chebi, pubchem dbsnp: entrez, clinvar, pharmgkb_variant, alphamissense, spliceai, pharmgkb_var_annotation clinvar: hgnc, mondo, hpo, dbsnp, orphanet, civic_variant, cellosaurus, clingen_variant alphamissense: uniprot, transcript mavedb: uniprot, hgnc, ensembl, transcript # deep-mutational-scanning functional variant scores (ACMG PS3/BS3); reach via gene/protein >> mavedb; per-variant score + hgvs_pro + license

VARIANT-EFFECT SCORES — look up by the variant's OWN key with biobtree_entry(dataset=..), NOT via >>chains:

conservation key "chr:pos" (GRCh38) per-position phyloP / GERP / phastCons (also covers non-missense/splice positions)

gnomad_variant key "chr:pos:ref:alt" (GRCh38) gnomAD v4.1 genomes allele freq (af, grpmax, per-ancestry); also xrefs dbsnp

revel key "chr:pos:ref:alt" (GRCh38) REVEL ensemble missense pathogenicity (0-1, higher = pathogenic)

saprot key "uniprot:protein_variant" SaProt protein-LM variant effect (LLR <=0, lower = more damaging), e.g. P01116:G12D

gwas: gwas_study, efo, dbsnp, hgnc, mondo gwas_study: gwas, efo, mondo mondo: gencc, clinvar, efo, mesh, hpo, clinical_trials, antibody, cellxgene, cellxgene_celltype, orphanet, mondoparent, mondochild, gwas, gwas_study, civic, intogen, cellosaurus, doid, mim, ncit, umls, medgen, gard, sctid, icd9, icd10cm, icd10who, icd11, nando, meddra, nord, uberon, ncrna_disease, panelapp_gene # disease cross-refs + disease_has_location anatomy, from the Mondo OBO doid: mondo, alliance_disease, doidparent, doidchild # Disease Ontology (now a full ontology w/ hierarchy); reach MONDO + its disease graph via the mondo<->doid bridge alliance_disease: hgnc, mgi, rgd, zfin, sgd, wormbase, flybase, xenbase, doid, pubmed # cross-species + human gene->disease (Alliance of Genome Resources); gene >> alliance_disease >> doid, or doid >> alliance_disease >> mgi/rgd/... for model-organism genes alliance_phenotype: mgi, rgd, wormbase, xenbase, mp, wbphenotype, xpo, pubmed # model-organism gene -> OBSERVED knockout/mutant phenotypes (distinct from the upheno ontology-translation path). Reach from the model-organism gene directly: mgi/rgd/wormbase/xenbase >> alliance_phenotype >> mp gencc: mondo, hpo, hgnc, ensembl clingen_gene_validity: hgnc, entrez, ensembl, mondo # ClinGen gene-disease validity tier (Definitive..Refuted) + MOI clingen_dosage: entrez, hgnc, ensembl, mondo, mim, pubmed # ClinGen haploinsufficiency/triplosensitivity per gene clingen_variant: clinvar, hgnc, entrez, ensembl, mondo, pubmed # ClinGen VCEP ACMG variant pathogenicity (clinvar bridges to dbsnp) panelapp: panelapp_gene # Genomics England clinical gene panels (per-panel master); panel >> panelapp_gene >> hgnc for the panel's genes panelapp_gene: panelapp, hgnc, ensembl, mim, mondo # one per (panel,gene), green/amber confidence + mode-of-inheritance; a gene's panels via >>hgnc (panelapp_gene) ; the panel's disease via mondo/mim clinical_trials: mondo, chembl_molecule pharmgkb: hgnc, dbsnp, mesh, pharmgkb_gene, pharmgkb_variant, pharmgkb_clinical, pharmgkb_guideline, pharmgkb_pathway pharmgkb_variant: pharmgkb_clinical, hgnc, mesh, dbsnp pharmgkb_gene: hgnc, entrez, ensembl, pharmgkb pharmgkb_clinical: dbsnp, hgnc, mesh, pharmgkb_variant, pharmgkb # pharmgkb = reverse drug→clinical edge (drug >> pharmgkb >> pharmgkb_clinical) pharmgkb_guideline: hgnc, pharmgkb pharmgkb_pathway: hgnc, pharmgkb pharmgkb_var_annotation: hgnc, entrez, ensembl, dbsnp, pubmed # per-publication variant-annotation evidence (finding sentence, PMID, significance, study stats) beneath pharmgkb_clinical; reach via gene or rsID ctd: mesh, ctd_gene_interaction, ctd_disease_association, pubchem ctd_gene_interaction: ctd, entrez, taxonomy, pubmed ctd_disease_association: ctd, mesh, mim, pubmed intact: uniprot, chebi, rnacentral string: uniprot, string_interaction string_interaction: string, uniprot biogrid: entrez, uniprot, refseq, taxonomy bgee: ensembl, uberon, cl, taxonomy, bgee_evidence bgee_evidence: bgee, uberon, cl cellxgene: cl, uberon, mondo, efo, taxonomy cellxgene_celltype: cl, uberon, mondo scxa: cl, uberon, taxonomy, ensembl, scxa_gene_experiment scxa_expression: ensembl, scxa, scxa_gene_experiment scxa_gene_experiment: ensembl, scxa, scxa_expression, cl hpa: ensembl, uniprot, hgnc, entrez, go, uberon, hpa_expression, hpa_pathology, hpa_antibody # Human Protein Atlas gene card: subcellular location (→go), specificity calls, top tissues hpa_expression: hpa, uberon, cellosaurus # per (gene,tissue/cell-line) RNA nTPM + IHC staining; reach genes-in-a-tissue via uberon >> hpa_expression hpa_pathology: hpa # per (gene,cancer) prognostic survival association hpa_antibody: hpa, ensembl # HPA validation antibody (reliability, antigen) rnacentral: uniprot, ensembl, intact, hgnc, refseq, ena, go # go = Rfam-projected GO annotations; rfam_id/rfam_description are attrs on the entry ncrna_disease: hgnc, ensembl, mondo, efo, pubmed # curated ncRNA->disease (LncRNADisease + HMDD); reach from the ncRNA gene ncrna_interaction: hgnc, ensembl, uniprot, pubmed # experimentally-supported ncRNA->protein interactions (NPInter) ncrna_drug: hgnc, ensembl, chembl_molecule, pubchem, pubmed # ncRNA drug-resistance / drug-target (ncRNADrug) reactome: ensembl, uniprot, chebi, go, reactomeparent, reactomechild rhea: chebi, uniprot, go go: ensembl, uniprot, reactome, msigdb, swisslipids, bgee, interpro, goparent, gochild, hpa, rnacentral hpo: clinvar, gencc, mondo, msigdb, orphanet, mim, hmdb, hgnc, hpoparent, hpochild, upheno efo: gwas, mondo, cellxgene, efoparent, efochild, ncrna_disease upheno: hpo, mp, zp, xpo, wbphenotype, fypo, uphenoparent, uphenochild # cross-species phenotype hub. A GENE's model-organism phenotypes are reached THROUGH hpo (genes are NOT linked directly to mp/upheno): >>hgnc>>hpo>>upheno>>mp (mouse), >>hgnc>>hpo>>upheno>>zp (zebrafish), ...>>xpo/wbphenotype/fypo. So gene->human HP phenotypes -> their cross-species equivalents. mp: upheno, mpparent, mpchild, alliance_phenotype # Mammalian Phenotype Ontology (mouse/rat). Reach from a gene via >>hgnc>>hpo>>upheno>>mp (NOT >>hgnc>>mp); observed model phenotypes via alliance_phenotype. zp: upheno, zpparent, zpchild # Zebrafish Phenotype Ontology. Reach from a gene via >>hgnc>>hpo>>upheno>>zp. xpo: upheno, xpoparent, xpochild, alliance_phenotype # Xenopus Phenotype Ontology wbphenotype: upheno, wbphenotypeparent, wbphenotypechild, alliance_phenotype # C. elegans Phenotype Ontology fypo: upheno, fypoparent, fypochild # Fission Yeast Phenotype Ontology uberon: bgee, cellxgene, cellxgene_celltype, swisslipids, uberonparent, uberonchild, hpa, hpa_expression cl: bgee, cellxgene, cellxgene_celltype, scxa, scxa_gene_experiment, clparent, clchild taxonomy: ensembl, uniprot, bgee, biogrid, ctd_gene_interaction, taxparent, taxchild mesh: pharmgkb, ctd, ctd_disease_association, pubchem, mondo, chembl_molecule, meshparent, meshchild eco: ecoparent, ecochild antibody: ensembl, uniprot, mondo, pdb msigdb: hgnc, entrez, go, hpo orphanet: hpo, uniprot, mondo, hgnc, clinvar, mim, mesh mim: clinvar, hpo, mondo, uniprot, ctd_disease_association, panelapp_gene hmdb: pubchem, hpo, chebi, uniprot collectri: hgnc # transcription factor → target gene interactions esm2_similarity: uniprot # protein structural similarity diamond_similarity: uniprot # protein sequence similarity cellphonedb: uniprot, ensembl, hgnc, pubmed # ligand-receptor pairs for cell-cell communication spliceai: hgnc pdb: uniprot, go, interpro, pfam, taxonomy, pubmed fantom5_promoter: ensembl, hgnc, entrez, uniprot, uberon, cl fantom5_enhancer: ensembl, uberon, cl fantom5_gene: ensembl, hgnc, entrez jaspar: uniprot, pubmed, taxonomy encode_ccre: taxonomy bao: chembl_activity, chembl_assay, baoparent, baochild brenda: uniprot, pubmed, brenda_kinetics, brenda_inhibitor brenda_kinetics: brenda brenda_inhibitor: brenda gtopdb: uniprot, hgnc, gtopdb_ligand, gtopdb_interaction # drug targets (GPCRs, ion channels, enzymes) gtopdb_ligand: pubchem, chebi, chembl_molecule, gtopdb_interaction # ligands/drugs with binding data gtopdb_interaction: gtopdb, gtopdb_ligand, pubmed # target-ligand binding with affinity values civic: entrez, ensembl, civic_variant, civic_evidence, civic_assertion # clinical interpretation of cancer variants civic_variant: civic, clinvar, civic_evidence, civic_assertion, transcript civic_evidence: civic_variant, civic, mondo, chembl_molecule, pubmed, clinical_trials civic_assertion: civic_variant, civic, mondo, chembl_molecule intogen: hgnc, entrez, ensembl, mondo, pubmed # cancer driver genes cellosaurus: taxonomy, uniprot, hgnc, mondo, orphanet, clinvar, dbsnp, uberon, cl, chebi, doi, patent, pubmed, depmap_dependency, hpa_expression # cell lines (CVCL) generif: entrez, pubmed # NCBI cited per-gene functional claims (RAG grounding) depmap: entrez, hgnc, ensembl # CRISPR gene essentiality aggregate (cancer dependency / target tractability) depmap_dependency: entrez, cellosaurus # per cell-line gene dependency (effect < -0.5)

FILTER SYNTAX: >>dataset[field operator value]

OPERATORS: == equals >>dataset[field=="value"] != not equals >>dataset[field!="value"]

   greater than     >>dataset[field>value]

< less than >>dataset[field<value]

= greater or equal >>dataset[field>=value] <= less or equal >>dataset[field<=value] contains string match >>dataset[field.contains("value")]

LOGICAL OPERATORS: && AND >>dataset[field1>5 && field2<10] || OR >>dataset[field=="A" || field=="B"] ! NOT >>dataset[!field] or >>dataset[!(field=="value")]

TYPE RULES:

• FLOAT: use decimal point (70.0 not 70)

• INT: no decimal (2 not 2.0)

• STRING: quote values ("Pathogenic", "PHASE3")

• BOOL: true/false (no quotes)

EXAMPLES:

chembl_molecule[highestDevelopmentPhase==4] # approved drugs chembl_molecule[highestDevelopmentPhase>=3] # Phase 3+ clinical_trials[phase=="PHASE3"] go[type=="biological_process"] clinvar[germline_classification=="Pathogenic"] reactome[name.contains("signaling")] gtopdb[type=="gpcr"] # GPCR targets gtopdb[type=="ion_channel"] # ion channel targets gtopdb_ligand[approved==true] # approved drugs only gtopdb_interaction[endogenous==true] # endogenous ligand interactions