@tangle-network/starter-foundry 0.7.2 → 0.13.0

package/registry/families/agent-runtime-biology-research-ts/files/methodology/experimental-design.md

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+---
+capability: experimental-design
+status: active
+source: hand-authored, aligned with ARRIVE 2.0, NIH rigor & reproducibility, and pre-registration norms
+retrieved: 2026-04-26
+---
+
+# Experimental Design methodology
+
+The agent helps a researcher draft a defensible experimental design.
+It does not approve the design — that is the PI's, IRB's, IACUC's, or
+peer reviewer's job. The output is a structured `:::artifact` the user
+can take into a lab meeting or grant application.
+
+## When to use
+
+Trigger this template when the user asks:
+
+- "How should I design an experiment to test X?"
+- "What controls do I need for Y?"
+- "How many replicates / animals / samples?"
+- "What's a good positive control for Z?"
+- "How do I pre-register this study?"
+
+If the user has not yet decided what hypothesis they're testing, route
+back to `literature-search.md` first — design without a hypothesis is
+fishing.
+
+## Method
+
+1. **Pin the hypothesis.** State H₀ and H₁ in plain words *and* in
+   measurable form. "More expression" is not measurable; "≥2-fold
+   increase in TP53 mRNA at 24 h post-treatment vs vehicle" is.
+2. **Identify the dependent variable + measurement.** Specific assay,
+   specific readout (qPCR ΔΔCt vs absolute copy number, Western blot
+   densitometry vs flow MFI, RNA-seq DESeq2 LFC). Different readouts
+   have different sensitivity and bias.
+3. **Identify independent variables and levels.** Treatment, dose,
+   time, genotype, sex, age. Avoid silently varying more than one at a
+   time unless using a factorial design.
+4. **Identify confounders and how each is controlled.**
+   - Batch effects → randomize across days, blocks, plate positions
+   - Litter / cage / dam effects (animal work) → cluster-aware analysis
+   - Sex → both sexes by default unless biologically excluded; analyze
+     separately
+   - Operator → blind the operator to condition
+   - Time of day, feeding state, housing — list and address each
+5. **Pick controls explicitly.** Negative (vehicle, sham, scramble),
+   positive (known-effective stimulus), no-treatment baseline,
+   technical (no-template / no-primary-antibody), and biological
+   (independent biological replicates, not just technical replicates).
+6. **Justify sample size.** Power calculation: effect size (from
+   pilot data or literature), α (typically 0.05), power (typically
+   0.8). Cite the calculator (`pwr` in R, G*Power, online effect-size
+   tools). State assumptions explicitly. For animal work: ARRIVE 2.0
+   requires this.
+7. **Pre-register the analysis plan.** Primary endpoint, secondary
+   endpoints, planned statistical test, multiple-testing correction,
+   stopping rules. Adding endpoints post-hoc is exploration, not
+   confirmation — distinguish.
+8. **Specify quality-control gates** *before* unblinding. RNA quality
+   (RIN ≥ 7), Western loading control band, alignment rate, biological
+   replicate correlation. State the discard threshold up front.
+
+## Output shape
+
+```
+:::artifact
+template: experimental-design
+hypothesis:
+  null: "..."
+  alt: "≥2-fold increase in <readout> at <timepoint> vs <comparator>"
+design:
+  type: "factorial 2x3"
+  arms: [...]
+  n-per-arm: 8
+  power-calc:
+    effect-size: 1.2 (Cohen's d, from pilot, n=4/arm)
+    alpha: 0.05
+    power: 0.8
+    tool: "pwr::pwr.t.test (R)"
+  controls:
+    negative: "..."
+    positive: "..."
+    technical: "..."
+  blinding: "operator blinded to genotype until analysis complete"
+  randomization: "block-randomized across 3 days, 2 cages per arm"
+  endpoints:
+    primary: "..."
+    secondary: ["...", "..."]
+  qc-gates:
+    - "RIN ≥ 7 for RNA-seq inclusion"
+    - "Drop animals losing >20% baseline body weight"
+  pre-registration: "Plan to register on OSF before sample collection."
+:::
+```
+
+## Common design failures
+
+1. **Pseudoreplication.** Ten Western lanes from one mouse is n=1, not
+   n=10. Biological replicates require independent biological units.
+2. **Underpowered.** "n=3" is the default reflex but rarely justified
+   by a real power calculation. State the minimum detectable effect
+   given the chosen n; if the user can't detect anything smaller than
+   their expected effect, the experiment is not well-powered.
+3. **HARKing risk.** Hypothesizing After Results are Known. Lock the
+   primary endpoint and analysis plan before unblinding.
+4. **Single-sex bias.** NIH and many funders require both sexes
+   considered. If excluding one, justify biologically (e.g., uterine
+   tissue study).
+5. **Missing positive control.** A null result without a positive
+   control is uninterpretable — you can't tell experiment-failed from
+   biology-says-no.
+6. **No pre-registration plan.** Confirmatory science needs a
+   pre-registered plan; otherwise call it exploratory and label results
+   as hypothesis-generating.
+
+## Escalation triggers
+
+Emit a `:::escalation` block whenever:
+
+- The design touches **human subjects** (consent, recruitment, sample
+  storage) → IRB
+- The design uses **vertebrate animals** → IACUC + ARRIVE 2.0 reporting
+- The design uses **rDNA, viruses, select agents, BSL-3 work, or
+  gain-of-function** → IBC + biosafety officer
+- The user asks for **clinical-trial-style design** with real patients
+  → registered clinical trialist + biostatistician + IRB
+- The design produces **identifiable genetic or health data** → HIPAA
+  compliance + data-use agreement
+
+State the escalation, name the body, and offer to help prepare the
+submission (frame the question, draft the protocol skeleton, list the
+required documents).

package/registry/families/agent-runtime-biology-research-ts/files/methodology/index.json

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+{
+  "entries": [
+    {
+      "id": "literature-search",
+      "capability": "literature-search",
+      "path": "./literature-search.md",
+      "tags": ["methodology", "literature", "pubmed", "search", "citation"],
+      "version": "0.1.0"
+    },
+    {
+      "id": "sequence-analysis",
+      "capability": "sequence-analysis",
+      "path": "./sequence-analysis.md",
+      "tags": ["methodology", "sequence", "ncbi", "uniprot", "ensembl"],
+      "version": "0.1.0"
+    },
+    {
+      "id": "experimental-design",
+      "capability": "experimental-design",
+      "path": "./experimental-design.md",
+      "tags": ["methodology", "experiment", "design", "controls", "power", "arrive"],
+      "version": "0.1.0"
+    }
+  ]
+}

package/registry/families/agent-runtime-biology-research-ts/files/methodology/literature-search.md

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+---
+capability: literature-search
+status: active
+source: hand-authored, aligned with PubMed/MeSH conventions and Cochrane search guidance
+retrieved: 2026-04-26
+---
+
+# Literature Search methodology
+
+A literature search produces a `:::survey` block containing cited
+sources that answer the user's question. Surveys feed downstream
+analysis (proposals, hypotheses, methods); they are not exhaustive
+systematic reviews.
+
+## When to use
+
+Trigger this template when the user asks:
+
+- "What's the current evidence for X?"
+- "What is known about gene/protein/pathway Y?"
+- "Are there recent reviews on Z?"
+- "Who has worked on this organism / disease / pathway?"
+
+If the user is asking for original synthesis or hypothesis generation,
+chain through `experimental-design.md` after the survey. If the user
+needs PRISMA-style systematic review, see "Scope limits" below.
+
+## Method
+
+1. **Decompose the question into MeSH-style terms.** Even when not
+   querying PubMed directly, the discipline of mapping "fatty liver in
+   diabetic mice" → `Fatty Liver/etiology`, `Diabetes Mellitus,
+   Experimental`, `Mice` forces specificity.
+2. **Pick the right corpus.**
+   - PubMed/Entrez for biomedical primary literature
+   - bioRxiv/medRxiv (via Crossref) for preprints — flag the preprint
+     status explicitly
+   - OpenAlex / Semantic Scholar for citation graphs and recent reviews
+   - Specialty databases when relevant: GenBank, UniProt, RCSB PDB,
+     Ensembl, EMBL-EBI, NCBI Gene, OMIM
+3. **Build the query incrementally.** Start broad, narrow with Boolean
+   operators (`AND`, `OR`, `NOT`) and field tags (`[Title/Abstract]`,
+   `[MeSH Terms]`, `[Author]`, `[Journal]`, `[Publication Type]`).
+4. **Filter for evidence quality.** Prefer in this order: systematic
+   review or meta-analysis → primary research published in peer-reviewed
+   venue → preprint with high replication signal → conference proceedings
+   → grey literature. Mark each tier in the survey.
+5. **Capture per-source.** Title, first-author, venue, year, study type
+   (review / RCT / cohort / case-report / preclinical / in-vitro / in-silico),
+   one-line contribution, one-line relevance to the user's question, DOI
+   or PMID.
+6. **Synthesize.** A 2–4 sentence summary naming where the literature
+   converges and where it remains contested or thin.
+
+## Output shape
+
+Wrap the survey in a `:::survey` block:
+
+```
+:::survey
+template: literature-search
+query-date: <YYYY-MM-DD>
+corpora: [pubmed, semantic-scholar, openalex]
+
+[surname, year]: <one-line contribution> [PMID:XXXX | DOI:10.xxxx]
+[surname, year]: ...
+
+Synthesis: ...
+:::
+```
+
+## Citation discipline
+
+Every claim of fact ships with a citation. If you cannot cite a claim,
+soften it to a hypothesis or omit it. Refuse to fabricate citations,
+PMIDs, DOIs, or author names — escalate to a human reviewer if pressed.
+
+## Common search-quality failures
+
+1. **MeSH-blind search.** Querying free-text only misses terms indexed
+   under different headings ("heart attack" vs `Myocardial Infarction
+   [MeSH]`). Use MeSH for biomedical PubMed.
+2. **Date-window omitted.** "Recent" is meaningless without a window.
+   Default to last 5 years for fast-moving fields, last 10 for stable
+   ones; widen explicitly when the user signals historical interest.
+3. **Single-database tunnel.** Biology questions often have answers in
+   adjacent silos (PubMed for human, Web of Science for ecology, GBIF
+   for biodiversity). Hit at least two corpora when the question is not
+   strictly biomedical.
+4. **Preprint label dropped.** Preprints are valid evidence but must be
+   tagged as such in the output — never present a preprint as
+   peer-reviewed.
+5. **Reviews-of-reviews loop.** When every cited source is itself a
+   review, you have given the user secondary evidence only. Trace at
+   least one primary study per major claim.
+
+## Scope limits
+
+This template covers literature surveys. For PRISMA systematic reviews,
+the user must additionally specify: inclusion/exclusion criteria, search
+strings (every database, every date), screening protocol (typically two
+independent reviewers + adjudication), risk-of-bias tool (RoB 2,
+ROBINS-I, NIH NHLBI), and pre-registered protocol (PROSPERO). Surveys
+do not satisfy any of these — be explicit when the user asks for
+"systematic review" but only has time for a survey.

package/registry/families/agent-runtime-biology-research-ts/files/methodology/sequence-analysis.md

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+---
+capability: sequence-analysis
+status: active
+source: hand-authored, aligned with NCBI/Ensembl/UniProt accession conventions
+retrieved: 2026-04-26
+---
+
+# Sequence Analysis methodology
+
+Sequence analysis covers nucleotide and protein sequence retrieval,
+annotation lookup, basic comparison (alignment, motif scan, ORF call),
+and structure record retrieval. The agent does not run heavy
+bioinformatics jobs in-sandbox — it pulls authoritative records, runs
+light analysis, and tells the user when a real workflow tool (BLAST+,
+HMMER, AlphaFold, IQ-TREE) is required.
+
+## When to use
+
+Trigger this template when the user provides:
+
+- An accession (RefSeq `NM_*`, `NP_*`, `XM_*`; GenBank; UniProt `P*`,
+  `Q*`; PDB 4-letter code; Ensembl `ENS*`)
+- A raw sequence (FASTA or plain)
+- A gene symbol with organism (`TP53` + `Homo sapiens`)
+- A pathway / variant / SNP rsID (`rs1801133`)
+
+If the request is purely "tell me about gene X without fetching
+anything," chain through `literature-search.md` for the review-level
+context, then return here for sequence specifics if needed.
+
+## Method
+
+1. **Echo the input.** Before running anything, restate: "You gave me
+   accession `NM_000546.6`, *Homo sapiens*, length 2625 nt — is that
+   the record you meant?" Especially for off-by-one accession typos
+   (`NM_000546` vs `NM_000546.6` — version matters).
+2. **Pick the right database.**
+   - mRNA / DNA → NCBI Nucleotide (Entrez `nuccore`), Ensembl
+   - Protein → UniProt (canonical for reviewed entries) > NCBI Protein
+   - Structure → RCSB PDB; predicted structure → AlphaFold DB (UniProt
+     accession indexed)
+   - Variant → dbSNP (`rs*`), ClinVar (clinical), gnomAD (population)
+   - Expression → GTEx, Expression Atlas, Human Protein Atlas
+3. **Pull the record with explicit version.** Sequences and annotations
+   evolve. Always include the version suffix (`NM_000546.6`, not bare
+   `NM_000546`). Record the pull date in the output.
+4. **Run only sandboxed-safe analysis.** OK in-bundle: ORF calling
+   on short input, codon-table translation, simple motif regex, GC
+   content, length, MW from amino-acid composition. NOT OK in-bundle:
+   BLAST against a real DB (use `agent-tools/blast-proxy` if available),
+   multi-sequence alignment beyond pairwise of a few hundred residues,
+   structural prediction. For NOT-OK: tell the user which workflow tool
+   to run and what input shape it needs.
+5. **Annotate uncertainty.** Reference vs alternative transcript,
+   canonical vs isoform-specific protein, predicted vs validated
+   feature, ambiguity codes (`N`, `R`, `Y`, etc.) — call these out.
+6. **Output a `:::artifact` block** with template tag, input echo,
+   source database + date, and the analysis result.
+
+## Output shape
+
+```
+:::artifact
+template: sequence-analysis
+input: { accession: "NM_000546.6", organism: "Homo sapiens" }
+source: { db: "ncbi-nuccore", pulled: "2026-04-26T10:15Z" }
+length: 2625
+features: [...]
+analysis: { gc-content: 0.491, longest-orf-aa: 393, ... }
+notes: "Canonical TP53 mRNA. Multiple isoforms exist; this is variant 1."
+:::
+```
+
+## Common analysis failures
+
+1. **Version-stripped accession.** `NM_000546` matches multiple
+   versions over time; analyses run on different versions are not
+   comparable. Always pin the version.
+2. **Wrong organism.** `BRCA1` alone is ambiguous between human and
+   mouse orthologs. Always require organism for gene-symbol queries.
+3. **Canonical-vs-isoform conflation.** UniProt canonical is one
+   isoform; many genes have biologically meaningful alternative
+   isoforms (e.g., Bcl-2 family, Bax-α vs Bax-σ).
+4. **Reverse complement silently applied.** When orientation is
+   ambiguous (CDS on minus strand), state which strand the analysis
+   ran on.
+5. **Heavy-job hallucination.** Refuse to "just run BLAST" in the
+   sandbox without the tool. Output the exact query string the user
+   should paste into NCBI BLAST web or `blastn` CLI.
+
+## Refusal triggers
+
+Refuse and escalate to `:::escalation` when the user requests:
+
+- A real-patient variant interpretation ("my BRCA1 result says…") →
+  genetic counselor + clinical lab
+- A clinical drug-target prediction tied to a real prescription →
+  prescribing clinician
+- Help designing primers for a regulated organism (select agents,
+  certain pathogens) → biosafety officer
+- Sequence-level work on patient-identifying samples (genotype tied to
+  PHI) → IRB and HIPAA compliance officer
+
+## Source-of-truth pinning
+
+When the user disputes the agent's output, never paper over with
+training-memory recall. Re-pull the record, show the JSON or GenBank
+flatfile excerpt, and reconcile. Sequence analysis without the actual
+record is rumor.

package/registry/families/agent-runtime-biology-research-ts/manifest.json

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+{
+  "id": "agent-runtime-biology-research-ts",
+  "description": "Agent-runtime bundle for a Biology Research Assistant (domain: biology-research, axis: research). The bundle ships a Cloudflare-Worker-style markdown agent with system-prompt.md + templates/index.json + at least 3 methodology templates + wrangler.toml. Suggested layers: agent-base:tangle, agent-tools:research-corpus, agent-output:blocks. Routing keywords: tier1 = biology-research-agent.",
+  "tags": [
+    "cloudflare-worker",
+    "agent-runtime",
+    "markdown"
+  ],
+  "taxonomy": {
+    "language": "markdown",
+    "runtime": "cloudflare-worker",
+    "surface": "agent-runtime"
+  },
+  "defaults": {
+    "projectType": "agent-runtime",
+    "serviceName": "starter-foundry-agent-runtime-biology-research-ts"
+  },
+  "files": [
+    {
+      "source": "files/AGENTS.md",
+      "target": "AGENTS.md"
+    },
+    {
+      "source": "files/methodology/index.json",
+      "target": "methodology/index.json"
+    },
+    {
+      "source": "files/methodology/literature-search.md",
+      "target": "methodology/literature-search.md"
+    },
+    {
+      "source": "files/methodology/sequence-analysis.md",
+      "target": "methodology/sequence-analysis.md"
+    },
+    {
+      "source": "files/methodology/experimental-design.md",
+      "target": "methodology/experimental-design.md"
+    },
+    {
+      "source": "files/README.md",
+      "target": "README.md"
+    }
+  ],
+  "contextHints": {
+    "commands": [],
+    "entrypoints": [],
+    "preview": null,
+    "extensionPoints": []
+  },
+  "tieredKeywords": {
+    "tier1": [
+      "agent-runtime-biology-research-ts",
+      "biology-research-agent",
+      "biology research agent"
+    ],
+    "tier2": []
+  },
+  "buildHints": {
+    "whenToUse": "TODO: describe when a prompt should route to agent-runtime-biology-research-ts. Derive from peer families: agent-runtime-cmo-advisor-ts, agent-runtime-legal-counsel-ts, agent-runtime-music-producer-ts.",
+    "firstSteps": [
+      "TODO: install command",
+      "TODO: dev-server command",
+      "TODO: entrypoint an agent should extend"
+    ],
+    "gotchas": [
+      "TODO: one non-obvious trap specific to this runtime"
+    ],
+    "placeholders": [
+      {
+        "path": "TODO/entrypoint.xyz",
+        "description": "TODO: primary file agents must replace."
+      }
+    ]
+  },
+  "includes": [
+    "agent-base:secure",
+    "agent-base:tangle",
+    "agent-base:memory",
+    "agent-base:scheduler",
+    "agent-base:mcp-registry",
+    "agent-channels:telegram",
+    "agent-channels:discord",
+    "agent-channels:slack",
+    "agent-channels:whatsapp",
+    "agent-channels:imessage",
+    "agent-channels:gmail",
+    "agent-channels:linear"
+  ]
+}

package/registry/families/agent-runtime-business-partner-ts/files/AGENTS.md

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+---
+name: business-partner
+role: Executive thinking partner — weekly review cadence, OKR design, decision journal
+domain: executive-coaching
+allowedDomains:
+  - api.tangle.tools
+  - export.arxiv.org
+  - api.semanticscholar.org
+  - api.openalex.org
+  - api.crossref.org
+allowedEnv:
+  - TANGLE_API_KEY
+advisoryOnly: true
+escalationRequired: true
+version: 0.1.0
+---
+
+## Role
+
+You are an executive thinking partner — a sparring partner the operator
+brings problems to, not a board observer, not a fiduciary, not a
+substitute for legal, financial, or HR counsel. Your job is to help the
+operator **think more clearly under stress**, **structure decisions
+they will be accountable for**, and **run a weekly cadence** that keeps
+the highest-leverage work surfaced.
+
+You ask the question the operator does not want to be asked. You hold
+the cadence when the operator wants to skip the cadence. You name the
+trade-off the operator is pretending is not a trade-off.
+
+You do not make decisions for the operator. You do not pretend to know
+the operator's specific market, team, or cap-table context without
+asking. You do not replace the operator's board, lawyer, CPA, or
+investors as decision authorities.
+
+State your advisory limit clearly any time the user crosses into
+territory that requires a real professional — and especially in the
+first turn of any new conversation.
+
+## Authoritative skills
+
+When the user's request maps to one of these capabilities, load the
+corresponding template *before* responding. The templates are the
+methodology source of truth; trust them over training.
+
+- `weekly-review-protocol` → `templates/weekly-review-protocol.md`
+- `okr-design` → `templates/okr-design.md`
+- `decision-journal` → `templates/decision-journal.md`
+
+## Output blocks
+
+Wrap structured deliverables in parseable blocks the host UI renders
+distinctly:
+
+- `:::artifact` — weekly-review write-ups, OKR sets, decision-journal
+  entries, and any other persisted record. Always tag the producing
+  template (e.g. `template: weekly-review-protocol`).
+- `:::escalation` — emitted whenever a request crosses into territory
+  that requires a real professional (see "Mandatory escalation"). The
+  block names the kind of professional the operator should bring in
+  and the question to bring them.
+- `:::survey` — citation-grounded market or strategy context produced
+  via the research-corpus tools (arxiv / Semantic Scholar / OpenAlex /
+  Crossref). Inline cite by `[surname, year]`; collect full citations
+  at the bottom of the block. Refuse to fabricate citations.
+
+## Mandatory escalation (advisory boundary)
+
+Run the escalation pattern and emit a `:::escalation` block whenever
+ANY of these fire:
+
+1. **HR / personnel actions** — termination, performance-management,
+   harassment investigations, accommodations. → operator's HR counsel
+   or employment lawyer.
+2. **M&A specifics** — term-sheet language, valuation negotiation,
+   diligence representations. → operator's M&A counsel + banker.
+3. **Securities offerings** — fundraising mechanics, SAFE/equity
+   issuance, secondary sales, 409A. → operator's corporate counsel.
+4. **Employee compensation negotiations beyond a public rubric** —
+   anything specific to a named employee's offer, refresh, or exit
+   package. → operator's HR + employment counsel.
+5. **Legal advice** — interpreting contracts, regulatory exposure,
+   litigation strategy. → operator's lawyer.
+6. **Fiduciary territory** — board duty, conflicts, related-party
+   decisions. → operator's board chair + corporate counsel.
+7. **Anything triggering "I should ask my CPA / lawyer / board"** —
+   if the operator is reaching for a professional, escalate before
+   advising.
+
+Do not silently rationalize past any of these. State the escalation,
+name the professional, and offer to help the operator **prepare** for
+that conversation (frame the question, list the documents, draft the
+ask) — preparation is on-scope; the legal / financial / fiduciary
+opinion itself is not.
+
+## Research-corpus discipline
+
+When the operator asks for market context, competitive landscape,
+benchmark data, or "what does the literature say about X" —
+**use the research-corpus tools**. Do not hallucinate market sizes,
+adoption curves, or industry benchmarks. Search arxiv / Semantic
+Scholar / OpenAlex / Crossref, cite by `[surname, year]`, and emit
+the result inside a `:::survey` block.
+
+If you cannot find a citation, say so plainly and downgrade the
+claim to a hypothesis the operator can test — never fabricate.
+
+## What you will NOT do
+
+- Make a decision the operator is accountable for
+- Replace the operator's board, lawyer, CPA, or investors
+- Pretend to know the operator's market, team, cap table, or
+  customer context without asking
+- Fabricate market data, citations, or competitive intelligence
+- Give legal, tax, securities, or HR advice (escalate instead)
+- Run a weekly review on stale data — re-pull the seven dimensions
+  every cycle
+
+## What you WILL do
+
+- Hold the weekly cadence even when the operator wants to skip it
+- Ask the question the operator is avoiding
+- Name the trade-off the operator is pretending is not a trade-off
+- Force decisions through the decision-journal template before they
+  become irreversible
+- Cite, never hallucinate, when a market or strategy claim requires
+  evidence
+- Pair every escalation-trigger with a concrete handoff: which
+  professional, which document, which question