12  Function Interpretation

This chapter focuses on how to use Step 5: Function Interpretation in FeatureMAP Shiny. The detailed method, parameter definitions, and result structure have already been introduced in R package-Function Annotation, so here we focus on the Shiny workflow itself.

Important

Prerequisites: Make sure Module Identification has finished successfully before starting this step.

12.1 Enter the Function Interpretation Page

After finishing Module Identification, click Next Step, or open Analysis → 5 Function Interpretation in the navigation bar.

The purpose of this step is to turn statistically supported modules into interpretable biology, using the module’s own metabolite evidence, optional PubMed literature, and a large language model.

12.2 Parameter Area

Section Field Default
Module Selection Significance metric (p-value / FDR) FDR
Significance cutoff 0.05
Annotation Mode Fast / Advanced Fast
Study Context Species, Biospecimen, Phenotype empty
Literature Use PubMed literature off
Years to search, NCBI API key 5
Large Language Model Provider (OpenAI / Google Gemini / SiliconFlow / Local) OpenAI
Model ID empty
Local base URL, shown for Local empty
API key empty
Important

Demo data: switch the metric to p-value. With the demo dataset, no module reaches FDR < 0.05 and exactly one module passes p-value < 0.05. If you keep the default FDR, the run finishes normally but reports that no module passed the cutoff. Set Significance metric to p-value to interpret that one module. The same caveat and its explanation are given in R package-Module Identification.

Important

Model ID must be a chat model name that the selected provider actually offers, for example gpt-4.1-mini for OpenAI. The ⓘ icon next to the section title links to each provider’s model list. Local targets any OpenAI-compatible endpoint (such as a self-hosted server), needs a Local base URL, and works without an API key.

Note

Study Context is optional but strongly recommended: species, biospecimen and phenotype are what turn a generic biochemical description into an interpretation of your study. The phenotype is also used as the query context when PubMed retrieval is enabled.

12.3 Fast Mode and Advanced Mode

The Annotation Mode switch chooses between the two pipelines described in R package-Function Annotation:

  • Fast – a two-call pipeline producing one interpretation per module. This is the cheaper and faster option, and the right one for a first pass.
  • Advanced – a multi-agent debate: a Proposer drafts 1–3 candidate hypotheses, a Skeptic challenges them over up to two rounds, and an Arbiter accepts or rejects each one.
Tip

In the app, Advanced mode is not a set of separate options: the per-module debate transcript and the cross-module synthesis are always produced as part of an Advanced run, and appear as their own result tabs.

12.4 Run Function Interpretation

Once the parameters are ready, click Run.

The app calls the model module by module, so this step is the slowest one and its runtime grows with the number of significant modules, with Advanced mode, and with PubMed enabled. If no module passes the selected cutoff, the run finishes normally and the result panel reports that nothing passed.

Note

API keys are entered per session and are used only for the current run; they are not stored in your results.

12.5 Result Area (Fast Mode)

In Fast mode the right panel shows one module at a time, chosen with the module selector in the toolbar.

Each report opens with the module title and a row of pills – module ID, hypothesis type, and confidence – followed by five sections:

Section Content
Function Interpretation The functional summary, plus the core driver (anchor) metabolites behind it
Biochemical Context Chemical-class profile, KEGG and HMDB pathway coverage, and the endogenous/exogenous origin profile
Module Statistics The supporting metabolites of the module and the global direction of change
Phenotype & Literature The phenotype relationship, plus clickable PMID links when PubMed was enabled
Evidence Strength The confidence label and the rationale behind it

12.6 Result Area (Advanced Mode)

In Advanced mode the right panel has three tabs.

12.6.1 Accepted Interpretations

The same report layout as Fast mode, but with two selectors: one for the module and one for the accepted hypothesis within that module. A module can therefore carry more than one accepted interpretation.

12.6.2 Debate History

An embedded chat-style transcript of the debate for the selected module, showing the Proposer, Skeptic and Arbiter turns in order. This is where you see why a hypothesis survived or was rejected. It is the same page that export_debate_html() writes in the R package.

12.6.3 Cross-Module Synthesis

An interactive network integrating the accepted hypotheses from all modules into thematic clusters, with links that are either proposed by the model from the hypothesis summaries or computed deterministically from metabolic-network edges and pathway overlap. It corresponds to res$module_synthesis and to export_synthesis_network_html() in the R package.

Each node is one accepted hypothesis, named <module>::<hypothesis>; node colour marks the thematic cluster and node size the confidence. The checkboxes above the plot switch between Biochemical links, Biology links and links supported by Both, and the panel on the right holds the integrated summary written across all modules. Hypotheses without any cross-module link are collected under Unlinked hypotheses at the bottom.

Note

The screenshot above does not come from the demo data. A cross-module synthesis only becomes meaningful when several modules carry accepted hypotheses, and the demo dataset yields a single significant module, which leaves nothing to link. The screenshot therefore shows an Advanced run on a larger real dataset, so that the clusters, the cross-module links and the integrated summary are visible. With the demo data this tab still opens, but it shows one node and no links.

Both HTML reports can be exported on the Results Download page.

12.8 Next Step

Once function interpretation is complete, click Results to download the generated tables, networks and reports.