Network Pharmacology

SciMiner Network Pharmacology

Build a transparent hypothesis, not a mechanism claim. Keep experimental, curated-database, predicted, literature, and computational evidence separate throughout the workflow.

Prerequisites and boundaries

• SCIMINER_API_KEY must be injected by the SciMiner gateway before skill execution. Use it directly as the X-Auth-Token for SciMiner tool calls; never print, copy, or persist the key.
• If SCIMINER_API_KEY is unavailable at runtime, stop and report that the gateway did not inject the required credential. Do not attempt to derive or locate the API key through other means.
• Resolve every SciMiner capability from the live tool-doc index at https://sciminer.tech/tool_api_files/ and read the selected *_api_doc.md immediately before invocation. That document is authoritative for provider/tool names, parameters, upload behavior, polling, and results.
• Return each successful task's share_url. Preserve its task_id and source-document URL in the project manifest.
• Treat network_report.html as mandatory for every completed analysis, including empty, negative, or partial-result analyses. Do not replace it with a prose-only answer, a CSV-only handoff, or a network image.
• Do not use a target prediction, a network centrality score, enrichment, or docking score as proof of binding, efficacy, synergy, causality, or clinical benefit.
• Do not call a tool with guessed parameters. Ask for missing required inputs or omit the optional analysis.

Inputs and project contract

Collect or create project_manifest.json before analysis. Record the project question, date, analyst, species, disease term and ontology ID, compound source, structures, access dates, database/tool versions, thresholds, and every exclusion.

Accept one of these input shapes:

1. A compound table with compound_id, name, and SMILES/InChIKey; optionally source herb, plant part, preparation, measured abundance, and exposure evidence.
2. A formula/herb list. First request or retrieve a traceable compound table; never invent constituents from an herb name.
3. A small molecule and disease/phenotype. Require a canonical disease term and species before disease-target analysis.
4. User-provided targets, PPI edges, omics results, or docking structures. Preserve their source and identifier namespace.

Read evidence-model.md before scoring, filtering, ranking, or interpreting results. Read sciminer-tool-routing.md before selecting a SciMiner capability.

Workflow

1. Resolve entities and scope

• Canonicalize compounds by structure, not display name. Preserve original names and aliases.
• Record herb Latin name, Chinese/common name, medicinal part, preparation, and formula role separately; do not merge them into a single label.
• Normalize genes and proteins to one primary namespace and report unmapped or one-to-many mappings.
• Resolve the disease to an ontology term. State whether the question concerns therapeutic mechanism, repurposing, toxicity, or a specific phenotype.
• Define a biologically defensible universe before overlap or enrichment work; for an omics study, it is normally the tested/detectable genes, not the full genome by default.

2. Build the component evidence table

• Assign component evidence tier: measured > curated/literature > database-listed > in-silico candidate.
• Use SciMiner tools for structure conversion, Lipinski/PAINS checks, ADMET, descriptors, or pKa only when they answer the study question. Do not apply universal OB/DL cutoffs mechanically.
• Keep rejected compounds and the reason in component_exclusions.csv.
• For a formula, retain herb-to-compound provenance so that apparent multi-herb convergence can be inspected.

3. Acquire and grade target evidence

• Prefer quantitative bioactivity or curated mechanism evidence. Use target prediction only as a hypothesis-generating lane.
• Use the live SciMiner target-prediction documentation for each compound. Store input structure, returned rank/score, model name, task ID, and share URL.
• Use a separate SciMiner off-target analysis for safety or promiscuity questions; do not present its result as disease efficacy evidence.
• For disease relevance, use independent genetics, functional, expression, pathway, clinical, and literature sources where available. If the SciMiner Life-Science Database Query skill is installed, route broad database retrieval through its minimum relevant sub-skills; otherwise document the public sources actually used.
• Create target_evidence.csv with one row per compound–target–evidence record, not one merged opaque score.

4. Construct and analyze the evidence network

• Build typed edges: herb→compound, compound→target, target→disease, target↔target, target→pathway, and compound→adverse-effect when available.
• Attach evidence_tier, evidence_type, source, access_date, score_or_value, and direction to every eligible edge. Use unknown rather than inferring activation or inhibition.
• Report graph size, isolated nodes, connected components, source composition, and confidence-filter sensitivity before selecting hubs or modules.
• Treat frequent network hubs (for example, TP53, AKT1, TNF, IL6) as generic candidates until disease relevance, tissue/cell context, and compound evidence justify their prioritization.
• Use render_network_report.py to make a standalone, interactive HTML report and a machine-readable JSON network. Supply node and edge tables rather than hand-drawing a network. If the evidence screen yields no eligible network, run the renderer without node/edge inputs so it records the empty-state outcome instead of omitting the HTML report.

5. Interpret pathways and biological context

• Perform enrichment on the declared foreground against the declared background and report method, multiple-testing adjustment, annotation release/date, and gene-ID conversion losses.
• Prefer disease-relevant modules and directional evidence over long lists of generic GO terms. Explain whether each proposed effect is direct, indirect, predicted, or unknown.
• Cross-check leading targets against tissue/cell context and any supplied transcriptomic/proteomic evidence. Do not conflate disease-associated expression with a causal drug target.

6. Add computational support only when justified

• Run docking only for a short, pre-specified compound–target set with target evidence, a credible structure and binding-site rationale.
• Use live SciMiner documentation for tools such as AutoDock Vina, DiffDock, or scoring tools. Record receptor structure ID, chain, ligand/protonation state, search box/site, tool/model, and task URL.
• Inspect pose plausibility and known activity where possible. Label docking as supporting computational evidence; never use it as standalone validation.

7. Report conclusions, negative findings, and validation

Deliver project_manifest.json, component_evidence.csv, target_evidence.csv, nodes.csv, edges.csv, network.json, network_report.html, and a concise narrative.

Required HTML report and verification

Make network_report.html the primary evidence handoff, not a supplementary graphic. Include the network with entity and evidence-tier legend, searchable/filterable entities, graph summary and connectedness, source/tier composition, all available derived observations, selected-node evidence details, provenance/share URLs, and explicit interpretation limits. Do not hide relevant dimensions behind a single chart or deliver an unexplained hairball. Keep conclusions clearly labelled as curated, predicted, computational, or unknown.

Run the renderer as the final artifact-generation step, then verify the exact file exists before responding:

python scripts/render_network_report.py --nodes /nodes.csv --edges /edges.csv --output-dir /report --title "Evidence-graded network for "
if (-not (Test-Path /report/network_report.html)) { throw "Network HTML report was not generated" }

For a documented empty or negative result, omit --nodes and --edges but still run the command with --output-dir and --title. Never invent placeholder nodes or edges to make the visual look complete. Link the generated HTML in the final handoff together with the manifest and raw tables.

State separately:

• robust observations;
• ranked but unverified hypotheses;
• contradictory or missing evidence;
• negative results, including no credible target, disconnected network, non-significant enrichment, or failed docking;
• the smallest discriminating experiment for each leading hypothesis (for example, target engagement, pathway readout, gene perturbation, or exposure assay).

Minimum output schema

Use these fields unless the source lacks a value:

component_evidence.csv: compound_id,name,structure,source_herb,component_tier,source,access_date,decision,reason
target_evidence.csv: compound_id,target_id,target_symbol,evidence_tier,evidence_type,score_or_value,direction,source,access_date,task_id,share_url
nodes.csv: id,label,type,evidence_tier,score,description
edges.csv: source,target,evidence_type,evidence_tier,weight,direction,source_ref

Use type values such as herb, compound, target, disease, pathway, and adverse_effect. Do not omit rows merely because their confidence is low; encode the confidence and filter transparently in views.

Visual and writing rules

• Use the interactive report for exploration and export a filtered, legible static figure for a manuscript. Never use a dense all-entity hairball as the sole figure.
• Use color for entity type and line style/opacity for evidence tier; include a legend and source counts.
• Make titles claim only the evidence level, for example: “Predicted and curated target network for …”, not “Mechanism of …”.
• Cite database/tool documents and access dates next to conclusions. Include SciMiner share URLs for every successful task.