TOOLS_REFERENCE.md

Immunotherapy Response Prediction - Tools Reference

Tools Used by Phase

Phase 1: Input Standardization & Cancer Context

Tool	Parameters	Response	Purpose
OpenTargets_get_disease_id_description_by_name	diseaseName	{data: {search: {hits: [{id, name, description}]}}}	Resolve cancer to EFO ID
MyGene_query_genes	query	{hits: [{_id, symbol, name, ensembl: {gene}}]}	Resolve gene to Ensembl/Entrez IDs
ensembl_lookup_gene	gene_id, species='homo_sapiens'	{data: {id, display_name, description, biotype}}	Gene details

Phase 2: TMB Analysis

Tool	Parameters	Response	Purpose
fda_pharmacogenomic_biomarkers	drug_name, biomarker, limit	{count, shown, results: [{Drug, Biomarker, TherapeuticArea, LabelingSection}]}	FDA TMB-H approvals

Phase 3: Neoantigen Analysis

Tool	Parameters	Response	Purpose
UniProt_get_function_by_accession	accession	List of strings	Protein function for neoantigen assessment
iedb_search_epitopes	organism_name, source_antigen_name	{status, data, count}	Known epitopes
EnsemblVEP_annotate_rsid	variant_id	VEP annotation with SIFT/PolyPhen	Variant impact

Phase 4: MSI/MMR Status

Tool	Parameters	Response	Purpose
fda_pharmacogenomic_biomarkers	biomarker='Microsatellite Instability', limit	FDA MSI-H approvals	MSI-H drug approvals

Phase 5: PD-L1 Expression

Tool	Parameters	Response	Purpose
HPA_get_cancer_prognostics_by_gene	gene_name='CD274'	Cancer prognostic data	PD-L1 prognostic context
HPA_get_rna_expression_by_source	gene_name, source_type, source_name (ALL 3 required)	Expression data	Baseline expression

Phase 6: Immune Microenvironment

Tool	Parameters	Response	Purpose
HPA_get_cancer_prognostics_by_gene	gene_name	Cancer prognostics	Immune gene prognostics
enrichr_gene_enrichment_analysis	gene_list (array), libs (array, REQUIRED)	Enrichment results	Immune pathway analysis

Phase 7: Mutation-Based Predictors

Tool	Parameters	Response	Purpose
cBioPortal_get_mutations	study_id, gene_list (string!)	{data: [{proteinChange, mutationType, studyId, ...}]}	Mutation prevalence

Phase 8: Clinical Evidence & ICI Options

Tool	Parameters	Response	Purpose
FDA_get_indications_by_drug_name	drug_name, limit	{meta, results}	FDA-approved indications
FDA_get_mechanism_of_action_by_drug_name	drug_name, limit	{meta, results}	Drug mechanism
FDA_get_clinical_studies_info_by_drug_name	drug_name, limit	{meta, results}	Clinical study data
OpenTargets_get_drug_mechanisms_of_action_by_chemblId	chemblId	{data: {drug: {mechanismsOfAction: {rows}}}}	Drug MOA
OpenTargets_get_associated_drugs_by_disease_efoId	efoId, size	{data: {disease: {knownDrugs: {count, rows}}}}	Drugs for cancer
OpenTargets_get_approved_indications_by_drug_chemblId	chemblId	Approved indications	Drug approvals
drugbank_get_drug_basic_info_by_drug_name_or_id	query, case_sensitive, exact_match, limit (ALL 4)	Drug info	Drug details
drugbank_get_targets_by_drug_name_or_drugbank_id	query, case_sensitive, exact_match, limit (ALL 4)	Drug targets	ICI targets
drugbank_get_pharmacology_by_drug_name_or_drugbank_id	query, case_sensitive, exact_match, limit (ALL 4)	Pharmacology	Drug pharmacology
clinical_trials_search	action='search_studies', condition, intervention, limit	{total_count, studies}	Active ICI trials
PubMed_search_articles	query, max_results	List of dicts	Literature evidence

Phase 9: Resistance Risk Assessment

Tool	Parameters	Response	Purpose
civic_search_evidence_items	therapy_name, disease_name	{data: {evidenceItems: {nodes}}}	Resistance evidence
gnomad_get_gene_constraints	gene_symbol	Gene constraint metrics	Gene essentiality

Key ICI Drug Reference

Drug	ChEMBL ID	DrugBank ID	Target
Pembrolizumab	CHEMBL3137343	DB09037	PD-1 (PDCD1)
Nivolumab	CHEMBL2108738	DB09035	PD-1 (PDCD1)
Atezolizumab	CHEMBL3707227	DB11595	PD-L1 (CD274)
Durvalumab	CHEMBL3301587	DB11714	PD-L1 (CD274)
Ipilimumab	CHEMBL1789844	DB06186	CTLA-4
Avelumab	CHEMBL3833373	DB11945	PD-L1 (CD274)
Cemiplimab	CHEMBL4297723	DB14716	PD-1 (PDCD1)

Key Gene IDs

Gene	Ensembl ID	Entrez ID	UniProt	Role
PDCD1 (PD-1)	ENSG00000188389	5133	Q15116	ICI target
CD274 (PD-L1)	ENSG00000120217	29126	Q9NZQ7	ICI target
CTLA4	ENSG00000163599	1493	P16410	ICI target
BRAF	ENSG00000157764	673	P15056	Driver mutation
STK11	ENSG00000118046	6794	Q15831	Resistance
PTEN	ENSG00000284792	5728	P60484	Resistance
JAK1	ENSG00000162434	3716	P23458	Resistance
JAK2	ENSG00000096968	3717	O60674	Resistance
B2M	ENSG00000166710	567	P61769	Resistance
KEAP1	ENSG00000079999	9817	Q14145	Resistance
POLE	ENSG00000177084	5426	Q07864	Sensitivity
MLH1	ENSG00000076242	4292	P40692	MMR
MSH2	ENSG00000095002	4436	P43246	MMR
MSH6	ENSG00000116062	2956	P52701	MMR
PMS2	ENSG00000122512	5395	P54278	MMR

Common Parameter Mistakes

Wrong	Correct	Tool
q	query	MyGene_query_genes
rsid	variant_id	EnsemblVEP_annotate_rsid
gene_list=['BRAF']	gene_list='BRAF'	cBioPortal_get_mutations
3 params	ALL 4 params required	All drugbank_* tools
no species	species='homo_sapiens'	ensembl_lookup_gene
genericName	drugName	OpenTargets_get_drug_id_description_by_name