Comprehensive literature research with target disambiguation, evidence grading, mandatory completeness checklist, and biological model synthesis. Produces detailed reports focused on content, not methodology.
Type: Strategy Skill (for AI agents)
Version: 5.0.0
Last Updated: 2026-02-04
| Feature | Description |
|---|---|
| Target Disambiguation | Resolve IDs, synonyms, naming collisions BEFORE literature search |
| Evidence Grading | T1-T4 tiers for every claim (mechanistic → mention) |
| Mandatory Completeness | 15 required sections; must state "limited evidence" if empty |
| Collision-Aware Search | High-precision seeds + negative filters for ambiguous names |
| Citation-Network First | For sparse targets, expand via citations before broad keyword search |
| Biological Model | Synthesize evidence into 3-5 testable hypotheses |
| Report-Only Output | Methodology in separate appendix only if requested |
| Scalable Bibliography | Narrative stays readable; full bibliography in JSON/CSV |
Apply when users:
- Ask "what does the literature say about [target/topic]?"
- Need comprehensive literature coverage on a biological target
- Request target profiles or druggability assessments
- Want research gaps and testable hypotheses identified
- Need literature for grant writing with evidence grades
Phase 0: CLARIFY
└─ Is this a biological target? What scope? Methods appendix needed?
Phase 1: TARGET DISAMBIGUATION (default ON for biological targets)
├─ Resolve official IDs (UniProt, Ensembl, NCBI, ChEMBL)
├─ Gather synonyms + identify naming collisions
├─ Get protein architecture, expression, pathways
└─ Output: Target Profile + Collision-aware search plan
Phase 2: LITERATURE SEARCH (internal - not shown in report)
├─ High-precision seed queries (build mechanistic core)
├─ Citation network expansion from seeds
├─ Collision-filtered broader queries
└─ Theme clustering + evidence grading
Phase 3: REPORT SYNTHESIS
├─ Progressive writing with mandatory sections
├─ Apply evidence grades (T1-T4)
└─ Generate biological model + testable hypotheses
OUTPUT:
- [topic]_report.md (main deliverable)
- [topic]_bibliography.json (full papers)
- methods_appendix.md (only if requested)
| Tier | Symbol | Criteria | Example |
|---|---|---|---|
| T1 | ★★★ | Mechanistic study with direct evidence | CRISPR KO + rescue |
| T2 | ★★☆ | Functional study showing role | siRNA phenotype |
| T3 | ★☆☆ | Association/screen hit | GWAS, DepMap |
| T4 | ☆☆☆ | Review/mention/text-mined | Review article |
In report:
ATP6V1A drives lysosomal acidification [★★★: PMID:12345678] and regulates
autophagy [★★☆: PMID:23456789].ALL 15 sections required - state "limited evidence" if data unavailable:
- Identity/Aliases - IDs, synonyms, collisions
- Protein Architecture - Domains, isoforms, sites
- Complexes/Partners - Interactors with evidence type
- Subcellular Localization - Locations with confidence
- Expression Profile - Tissues, specificity
- Core Mechanisms - Function with evidence grades
- Model Organism Evidence - KO phenotypes or "none found"
- Human Genetics/Variants - Constraints, ClinVar, GWAS
- Disease Links - With evidence strength grades
- Pathogens - Or "none identified"
- Key Assays/Readouts - Available assays
- Research Themes - ≥3 papers per theme
- Open Questions/Gaps - What's unknown
- Biological Model - Integrated synthesis + 3-5 hypotheses
- Conclusions - Confidence assessment
| File | Content | Generated |
|---|---|---|
[topic]_report.md |
Main narrative report | Always (default deliverable) |
[topic]_bibliography.json |
Full deduplicated papers | Always |
[topic]_bibliography.csv |
Tabular bibliography | Always |
methods_appendix.md |
Methodology details | Only if user requests |
| File | Purpose |
|---|---|
| SKILL.md | Complete strategy guide |
| QUICK_REFERENCE.md | One-page cheat sheet |
| TOOL_NAMES_REFERENCE.md | Database tool names |
| README.md | Overview (this file) |
PubMed_search_articles, EuropePMC_search_articles (use source='PPR' for preprints), openalex_literature_search, SemanticScholar_search_papers
PubMed_get_cited_by → EuropePMC_get_citations
PubMed_get_related → SemanticScholar_search_papers
UniProt_*, InterPro_get_protein_domains, GTEx_*, HPA_*, GO_*, Reactome_*, OpenTargets_*
| Previous | Enhanced |
|---|---|
| Literature search first | Target disambiguation first (default ON) |
| All papers treated equally | Evidence grading (T1-T4) |
| Optional sections | Mandatory completeness checklist |
| Simple keyword search | Collision-aware query strategy |
| Keyword expansion | Citation-network-first for sparse targets |
| Embedded methodology | Report-only; methodology in appendix |
| Inline bibliography | Separate scalable JSON/CSV files |
| Descriptive report | Biological model + testable hypotheses |
| Any OA check method | Best-effort OA with clear labeling |
- All 15 mandatory sections present (or marked "limited evidence")
- Evidence grades applied to all major claims
- Target identifiers resolved
- Naming collisions documented
- ≥3 papers per research theme (or noted as insufficient)
- Biological model synthesized
- ≥3 testable hypotheses with experiments
- Bibliography files generated
- Methodology NOT in main report
Section with proper evidence grading:
## 6. Core Mechanisms
### 6.1 Molecular Function
ATP6V1A is the catalytic A subunit of the V-ATPase complex, responsible for
ATP hydrolysis that drives proton translocation [★★★: PMID:12345678].
**Evidence Quality**: Strong (5 mechanistic, 2 functional studies)
### 6.2 Biological Role
V-ATPase acidification of lysosomes is essential for:
- Autophagosome-lysosome fusion [★★★: PMID:23456789]
- mTORC1 activation via amino acid sensing [★★☆: PMID:34567890]
- Bone resorption by osteoclasts [★★★: PMID:45678901]Testable hypothesis:
| # | Hypothesis | Perturbation | Readout | Expected | Priority |
|---|------------|--------------|---------|----------|----------|
| 1 | ATP6V1A loss impairs autophagy | siRNA knockdown | LC3 puncta, p62 levels | ↑LC3-II, ↑p62 | HIGH |
| 2 | V-ATPase inhibition blocks mTORC1 | Bafilomycin A1 | S6K phosphorylation | ↓pS6K | HIGH |- Read SKILL.md for complete strategy
- Use QUICK_REFERENCE.md during execution
- Check TOOL_NAMES_REFERENCE.md for exact tool names
Version 5.0.0 - Enhanced with target disambiguation, evidence grading, and biological model synthesis