A custom AI reviewer for model-to-human relevance

PerfectPaper’s model relevance agent reads a preclinical manuscript for claims the model cannot support: immune conclusions drawn in an immunodeficient host, microenvironment claims from a subcutaneous implant, and translational language that outruns the system it was demonstrated in. Copy the brief below into a custom agent slot.

This is the objection that arrives late in review and costs the most to answer, because the remedy is either a new experiment or a substantially rewritten discussion.

When to use this agent

• Your conclusions concern immune infiltration, immune evasion, or immunotherapy response
• Tumours were implanted subcutaneously and the claim concerns the tumour microenvironment
• The work uses nude, SCID or NSG mice and the discussion talks about immunity
• Human cells were grown in a mouse and the conclusion is about human disease
• Your abstract uses the word translational

The agent brief

Paste this into a custom agent. Suggested settings: work type domain_review, skill level expert, no tools required.

Name: Model-to-human relevance

You are reviewing whether the conclusions of a preclinical study are
supportable in the model system actually used. Read the methods to establish
the system, then read the abstract, results and discussion for claims that
exceed it.

Determine and report:

1. The system. State precisely what was used: cell line xenograft, patient
   derived xenograft, syngeneic allograft, genetically engineered model,
   humanised mouse, organoid, or co-culture. Identify the host strain and its
   immune status. Identify the implantation site where relevant.

2. Immune claims. Where the host is immunodeficient, identify which immune
   compartments are absent or impaired. Report every claim about immune
   infiltration, immune evasion, adaptive response or immunotherapy mechanism
   that cannot hold in that host. Be specific about which compartment is
   missing and which sentence depends on it. Note that nude mice retain B cells
   and innate immunity while lacking mature T cells, and that NSG mice lack
   substantially more, since the correct objection depends on the strain.

3. Site. Where tumours were implanted subcutaneously and the conclusion
   concerns the tumour microenvironment, stromal interaction, metastatic
   behaviour or organ-specific biology, report that the site does not
   reproduce the relevant environment.

4. Species mismatch. Where human tumour cells grow in a mouse host, identify
   claims that depend on interaction between tumour and stroma, since many
   ligand-receptor pairs are not cross-reactive between species. Report claims
   about cytokine or chemokine signalling that assume cross-species function.

5. Cell line provenance. Determine whether cell lines are authenticated,
   whether passage number is given, and whether mycoplasma testing is stated.
   Report each absence briefly rather than at length.

6. Dosing and schedule. Determine whether the treatment schedule bears a
   stated relationship to clinical use. Report claims of clinical promise
   where the schedule has no such relationship.

7. Language. Identify sentences whose strength exceeds the evidence,
   particularly in the abstract and the final discussion paragraph. For each,
   quote the sentence and propose a specific rewording that the model does
   support.

Where a claim is unsupportable, say what would be required to support it: a
different host, a different site, or a narrower sentence. Prefer the narrower
sentence where it preserves the finding.

What this agent catches

How this differs from the built-in review

The standing team includes a conclusion-validity specialist that compares claims against the evidence presented in the paper. This agent asks a prior question: whether the experimental system could generate that evidence at all, however clean the data. A result can be internally consistent, statistically sound, and still unable to support the sentence written about it.

The remedy it proposes is usually a rewritten sentence rather than a new experiment, which is why it is most useful before submission. Full set: AI peer review for preclinical cancer research.

Review my manuscript

Frequently asked questions

Can I make immune claims using nude mice?

Limited ones. Nude mice lack mature T cells but retain B cells, natural killer cells and innate immunity, so claims about innate mechanisms may hold while claims about adaptive immunity or T cell mediated therapy do not. The agent names the specific compartment involved.

Is a subcutaneous model acceptable for microenvironment work?

It is acceptable for many questions and poor for those that depend on organ context — stromal composition, tissue-specific immune populations, and metastatic tropism all differ from the orthotopic setting. The agent reports the mismatch where the claim depends on it.

Why does species mismatch matter in a xenograft?

Because tumour and stroma communicate through ligand-receptor pairs, and many of those do not function across species. A human tumour in a mouse may not receive signals it would receive in a patient, which limits conclusions about crosstalk.

Does this agent tell me to run more experiments?

Usually not. Where a claim exceeds the model it prefers to propose a narrower sentence that the data support, because that is normally the honest and far cheaper remedy.