Comprehensive Target Intelligence Gatherer

Gather complete target intelligence by exploring 9 parallel research paths. Supports targets identified by gene symbol, UniProt accession, Ensembl ID, or gene name.

KEY PRINCIPLES

:

Report-first approach

- Create report file FIRST, then populate progressively

Tool parameter verification

- Verify params via

get_tool_info

before calling unfamiliar tools

Evidence grading

- Grade all claims by evidence strength (T1-T4). See

EVIDENCE_GRADING.md

Citation requirements

- Every fact must have inline source attribution

Mandatory completeness

- All sections must exist with data minimums or explicit "No data" notes

Disambiguation first

- Resolve all identifiers before research

Negative results documented

- "No drugs found" is data; empty sections are failures

Collision-aware literature search

- Detect and filter naming collisions

English-first queries

- Always use English terms in tool calls, even if the user writes in another language. Translate gene names, disease names, and search terms to English. Only try original-language terms as a fallback if English returns no results. Respond in the user's language

When to Use This Skill

Apply when users:

Ask about a drug target, protein, or gene

Need target validation or assessment

Request druggability analysis

Want comprehensive target profiling

Ask "what do we know about [target]?"

Need target-disease associations

Request safety profile for a target

When NOT to use

Simple protein lookup, drug-only queries, disease-centric queries, sequence retrieval, structure download -- use specialized skills instead. Phase 0: Tool Parameter Verification (CRITICAL) BEFORE calling ANY tool for the first time , verify its parameters: tool_info = tu . tools . get_tool_info ( tool_name = "Reactome_map_uniprot_to_pathways" )

Reveals: takes id not uniprot_id

Known Parameter Corrections

Tool

WRONG Parameter

CORRECT Parameter

Reactome_map_uniprot_to_pathways

uniprot_id

id

ensembl_get_xrefs

gene_id

id

GTEx_get_median_gene_expression

gencode_id

only

gencode_id

+

operation="median"

OpenTargets_*

ensemblID

ensemblId

(camelCase)

STRING_get_protein_interactions

single ID

protein_ids

(list),

species

intact_get_interactions

gene symbol

identifier

(UniProt accession)

GTEx Versioned ID Fallback (CRITICAL)

GTEx often requires versioned Ensembl IDs. If

ENSG00000123456

returns empty, try

ENSG00000123456.{version}

from

ensembl_lookup_gene

.

Critical Workflow Requirements

1. Report-First Approach (MANDATORY)

DO NOT

show the search process or tool outputs to the user. Instead:

Create the report file FIRST

(

[TARGET]_target_report.md

) with all section headers and

[Researching...]

placeholders. See

REPORT_FORMAT.md

for template.

Progressively update

each section as data is retrieved.

Methodology in appendix only

- create separate

[TARGET]_methods_appendix.md

if requested.

2. Evidence Grading (MANDATORY)

Grade every claim by evidence strength using T1-T4 tiers. See

EVIDENCE_GRADING.md

for tier definitions, required locations, and citation format.

Core Strategy: 9 Research Paths

Target Query (e.g., "EGFR" or "P00533")

|

+- IDENTIFIER RESOLUTION (always first)

| +- Check if GPCR -> GPCRdb_get_protein

|

+- PATH 0: Open Targets Foundation (ALWAYS FIRST - fills gaps in all other paths)

|

+- PATH 1: Core Identity (names, IDs, sequence, organism)

| +- InterProScan_scan_sequence for novel domain prediction

+- PATH 2: Structure & Domains (3D structure, domains, binding sites)

| +- If GPCR: GPCRdb_get_structures (active/inactive states)

+- PATH 3: Function & Pathways (GO terms, pathways, biological role)

+- PATH 4: Protein Interactions (PPI network, complexes)

+- PATH 5: Expression Profile (tissue expression, single-cell)

+- PATH 6: Variants & Disease (mutations, clinical significance)

| +- DisGeNET_search_gene for curated gene-disease associations

+- PATH 7: Drug Interactions (known drugs, druggability, safety)

| +- Pharos_get_target for TDL classification (Tclin/Tchem/Tbio/Tdark)

| +- BindingDB_get_ligands_by_uniprot for known ligands

| +- PubChem_search_assays_by_target_gene for HTS data

| +- If GPCR: GPCRdb_get_ligands (curated agonists/antagonists)

| +- DepMap_get_gene_dependencies for target essentiality

+- PATH 8: Literature & Research (publications, trends)

For detailed code implementations of each path, see

IMPLEMENTATION.md

.

Identifier Resolution (Phase 1)

Resolve ALL identifiers before any research path. Required IDs:

UniProt accession

(for protein data, structure, interactions)

Ensembl gene ID

+ versioned ID (for Open Targets, GTEx)

Gene symbol

(for DGIdb, gnomAD, literature)

Entrez gene ID

(for KEGG, MyGene)

ChEMBL target ID

(for bioactivity)

Synonyms/full name

(for collision-aware literature search)

After resolution, check if target is a GPCR via

GPCRdb_get_protein

. See

IMPLEMENTATION.md

for resolution and GPCR detection code.

PATH 0: Open Targets Foundation (ALWAYS FIRST)

Populates baseline data for Sections 5, 6, 8, 9, 10, 11 before specialized queries.

Endpoint

Report Section

Data Type

OpenTargets_get_diseases_phenotypes_by_target_ensemblId

8

Diseases/phenotypes

OpenTargets_get_target_tractability_by_ensemblId

9

Druggability assessment

OpenTargets_get_target_safety_profile_by_ensemblId

10

Safety liabilities

OpenTargets_get_target_interactions_by_ensemblId

6

PPI network

OpenTargets_get_target_gene_ontology_by_ensemblId

5

GO annotations

OpenTargets_get_publications_by_target_ensemblId

11

Literature

OpenTargets_get_biological_mouse_models_by_ensemblId

8/10

Mouse KO phenotypes

OpenTargets_get_chemical_probes_by_target_ensemblId

9

Chemical probes

OpenTargets_get_associated_drugs_by_target_ensemblId

9

Known drugs

PATH 1: Core Identity

Tools

:

UniProt_get_entry_by_accession

,

UniProt_get_function_by_accession

,

UniProt_get_recommended_name_by_accession

,

UniProt_get_alternative_names_by_accession

,

UniProt_get_subcellular_location_by_accession

,

MyGene_get_gene_annotation

Populates

Sections 2 (Identifiers), 3 (Basic Information)

PATH 2: Structure & Domains

Use 3-step structure search chain (do NOT rely solely on PDB text search):

UniProt PDB cross-references

(most reliable)

Sequence-based PDB search

(catches missing annotations)

Domain-based search

(for multi-domain proteins)

AlphaFold

(always check)

Tools

:

UniProt_get_entry_by_accession

(PDB xrefs),

get_protein_metadata_by_pdb_id

,

PDB_search_similar_structures

,

alphafold_get_prediction

,

InterPro_get_protein_domains

,

UniProt_get_ptm_processing_by_accession

GPCR targets

Also query

GPCRdb_get_structures

for active/inactive state data.

Populates

Section 4 (Structural Biology)

See

IMPLEMENTATION.md

for the 3-step chain code.

PATH 3: Function & Pathways

Tools

:

GO_get_annotations_for_gene

,

Reactome_map_uniprot_to_pathways

,

kegg_get_gene_info

,

WikiPathways_search

,

enrichr_gene_enrichment_analysis

Populates

Section 5 (Function & Pathways)

PATH 4: Protein Interactions

Tools

:

STRING_get_protein_interactions

,

intact_get_interactions

,

intact_get_complex_details

,

BioGRID_get_interactions

,

HPA_get_protein_interactions_by_gene

Minimum

20 interactors OR documented explanation.

Populates

Section 6 (Protein-Protein Interactions)

PATH 5: Expression Profile

GTEx with versioned ID fallback + HPA as backup. For comprehensive HPA data, also query cell line expression comparison.

Tools

:

GTEx_get_median_gene_expression

,

HPA_get_rna_expression_by_source

,

HPA_get_comprehensive_gene_details_by_ensembl_id

,

HPA_get_subcellular_location

,

HPA_get_cancer_prognostics_by_gene

,

HPA_get_comparative_expression_by_gene_and_cellline

,

CELLxGENE_get_expression_data

Populates

Section 7 (Expression Profile)

See

IMPLEMENTATION.md

for GTEx fallback and HPA extended expression code.

PATH 6: Variants & Disease

Separate SNVs from CNVs in ClinVar results. Integrate DisGeNET for curated gene-disease association scores.

Tools

:

gnomad_get_gene_constraints

,

clinvar_search_variants

,

OpenTargets_get_diseases_phenotypes_by_target_ensembl

,

DisGeNET_search_gene

,

civic_get_variants_by_gene

,

cBioPortal_get_mutations

Required

All 4 constraint scores (pLI, LOEUF, missense Z, pRec).

Populates

Section 8 (Genetic Variation & Disease)

PATH 7: Druggability & Target Validation

Comprehensive druggability assessment including TDL classification, binding data, screening data, and essentiality.

Tools

:

OpenTargets_get_target_tractability_by_ensemblID

,

DGIdb_get_gene_druggability

,

DGIdb_get_drug_gene_interactions

,

ChEMBL_search_targets

,

ChEMBL_get_target_activities

,

Pharos_get_target

,

BindingDB_get_ligands_by_uniprot

,

PubChem_search_assays_by_target_gene

,

DepMap_get_gene_dependencies

,

OpenTargets_get_target_safety_profile_by_ensemblID

,

OpenTargets_get_biological_mouse_models_by_ensemblID

GPCR targets

Also query

GPCRdb_get_ligands

.

Populates

Sections 9 (Druggability), 10 (Safety), 12 (Competitive Landscape)

Key Data Sources for Druggability

Source

What It Provides

Pharos TDL

Tclin/Tchem/Tbio/Tdark classification

BindingDB

Experimental Ki/IC50/Kd values

PubChem BioAssay

HTS screening hits and dose-response

DepMap

CRISPR essentiality across cancer cell lines

ChEMBL

Bioactivity records and compound counts

See

IMPLEMENTATION.md

for detailed code and

REFERENCE.md

for complete tool parameter tables.

PATH 8: Literature & Research (Collision-Aware)

Detect collisions

- Check if gene symbol has non-biological meanings

Build seed queries

- Symbol in title with bio context, full name, UniProt accession

Apply collision filter

- Add NOT terms for off-topic meanings

Expand via citations

- For sparse targets (<30 papers), use citation network

Classify by evidence tier

- T1-T4 based on title/abstract keywords

Tools

:

PubMed_search_articles

,

PubMed_get_related

,

EuropePMC_search_articles

,

EuropePMC_get_citations

,

PubTator3_LiteratureSearch

,

OpenTargets_get_publications_by_target_ensemblID

Populates

Section 11 (Literature & Research Landscape) See IMPLEMENTATION.md for collision-aware search code. Retry Logic & Fallback Chains Primary Tool Fallback 1 Fallback 2 ChEMBL_get_target_activities GtoPdb_get_target_ligands OpenTargets drugs intact_get_interactions STRING_get_protein_interactions OpenTargets interactions GO_get_annotations_for_gene OpenTargets GO MyGene GO GTEx_get_median_gene_expression HPA_get_rna_expression Document as unavailable gnomad_get_gene_constraints OpenTargets constraint - DGIdb_get_drug_gene_interactions OpenTargets drugs GtoPdb NEVER silently skip failed tools. Always document failures and fallbacks in the report. Completeness Audit (REQUIRED before finalizing) Run the checklist in EVIDENCE_GRADING.md before finalizing any report: Data minimums met for PPIs, expression, diseases, constraints, druggability Negative results documented explicitly T1-T4 grades in Executive Summary, Disease Associations, Key Papers, Recommendations Every data point has source attribution Report Template Create [TARGET]_target_report.md with all 15 sections initialized. See REPORT_FORMAT.md for the full template with section headers, table formats, and completeness checklist. Initial file structure:

1. Executive Summary ## 9. Druggability & Pharmacology

2. Target Identifiers ## 10. Safety Profile

3. Basic Information ## 11. Literature & Research

4. Structural Biology ## 12. Competitive Landscape

5. Function & Pathways ## 13. Summary & Recommendations

6. Protein-Protein Interactions ## 14. Data Sources & Methodology

7. Expression Profile ## 15. Data Gaps & Limitations

8. Genetic Variation & Disease

Quick Reference: Tool Parameters Tool Parameter Notes Reactome_map_uniprot_to_pathways id NOT uniprot_id ensembl_get_xrefs id NOT gene_id GTEx_get_median_gene_expression gencode_id , operation Try versioned ID if empty OpenTargets_* ensemblId camelCase, not ensemblID STRING_get_protein_interactions protein_ids , species List format for IDs intact_get_interactions identifier UniProt accession Reference Files File Contents IMPLEMENTATION.md Detailed code for identifier resolution, GPCR detection, each PATH implementation, retry logic EVIDENCE_GRADING.md T1-T4 tier definitions, citation format, completeness audit checklist, data minimums REPORT_FORMAT.md Full report template with all 15 sections, table formats, section-specific guidance REFERENCE.md Complete tool reference (225+ tools) organized by category with parameters EXAMPLES.md Worked examples: EGFR full profile, KRAS druggability, target comparison, CDK4 validation, Alzheimer's targets