comparative-genomics-agent

name	comparative-genomics-agent
description	Compare a gene across multiple species — find orthologs, retrieve sequences, compute alignments, and summarize conservation

Perform a multi-species comparative genomics analysis for: $ARGUMENTS

Use the MCP tools available to you to find orthologs, retrieve sequences, align them, and report on conservation. Follow the steps below in order. If a step fails for a particular species, note the gap and continue with the remaining species.

Input Parsing

Parse the user input to identify:

1. Gene identifier — a gene symbol (e.g., TP53), Ensembl gene ID (e.g., ENSG00000141510), or NCBI Gene ID
2. Species list — extract species names. Convert common names to Ensembl species names:
   • human → homo_sapiens
   • mouse → mus_musculus
   • rat → rattus_norvegicus
   • zebrafish → danio_rerio
   • chicken → gallus_gallus
   • frog → xenopus_tropicalis
   • fly / fruit fly → drosophila_melanogaster
   • worm → caenorhabditis_elegans
   • dog → canis_lupus_familiaris
   • cat → felis_catus
   • pig → sus_scrofa
   • cow → bos_taurus

If the user says "across vertebrates" or similar, use: human, mouse, zebrafish, chicken (4 representative species). If no species are specified, default to: human, mouse, zebrafish.

Data Gathering Steps

1. Reference Gene Information

• If the input is a gene symbol, call ensembl_lookup_gene with the symbol and species homo_sapiens (or the first species listed) to get the Ensembl gene ID.
• Call datasets_summary_gene with the gene symbol (taxon: human) for NCBI gene metadata (full name, summary).
• Note the reference Ensembl gene ID for the next step.

2. Find Orthologs

• Call ensembl_get_homologs with the reference Ensembl gene ID, homology_type: "orthologues".
• From the results, extract the ortholog Ensembl gene IDs for each of the requested target species.
• If a requested species has no ortholog in the results, note it as "No ortholog found."
• Record the percent identity values reported by Ensembl for each ortholog pair.

3. Retrieve Protein Sequences

For the reference gene and each ortholog found:

• Call ensembl_get_sequence with the Ensembl gene ID, seq_type: "protein", format: "json".
• Store the protein sequence and its length.

If a protein sequence is not available for a gene ID, try the canonical transcript ID instead.

4. Pairwise Alignments

For each ortholog protein sequence, align it against the reference (human) protein:

• Call sequence_align with the two protein sequences, sequence_type: "protein", mode: "global".
• Record: alignment score, percent identity, gap count, alignment length.

If there are 3+ species, also consider one key pairwise comparison between distant species (e.g., mouse vs zebrafish) to show the range of divergence.

5. Sequence Statistics (Optional)

For the reference protein:

• Call sequence_stats with the protein sequence to get molecular weight, amino acid composition.
• Note any unusual composition differences across species if evident from the alignments.

6. Domain Conservation Check (Optional)

• Call interpro_get_domains with the UniProt accession (if known) or look up via uniprot_search for the reference gene.
• Note which key functional domains exist — these regions are expected to be highly conserved.

Report Format

Present the analysis as a structured comparative genomics report:

# Comparative Genomics Report: [GENE SYMBOL]

## Gene Overview
- Full name, function summary (from NCBI/Ensembl)
- Reference species and Ensembl gene ID
- Number of species analyzed

## Ortholog Summary

| Species | Ensembl Gene ID | Protein Length | % Identity to [Reference] | % Positives |
|---------|-----------------|----------------|---------------------------|-------------|
| Human (reference) | ENSG... | 393 aa | — | — |
| Mouse | ENSMUSG... | 390 aa | 77.8% | 85.2% |
| Zebrafish | ENSDARG... | 373 aa | 52.1% | 66.3% |

## Pairwise Alignments

For each species pair aligned:
- **[Reference] vs [Species]**: X% identity, Y gaps, alignment length Z
- Key observations: conserved regions, notable insertions/deletions

## Conservation Analysis

Summarize the overall conservation pattern:
- Which regions are most conserved (relate to known domains if domain data was retrieved)
- Which regions show the most divergence
- Overall trend: is this gene highly conserved, moderately conserved, or rapidly evolving?
- Note any species-specific insertions or deletions

## Functional Domain Context
If domain data was retrieved:
- List key domains with positions
- Note whether these domains span the conserved regions

## Evolutionary Insights
Brief interpretation:
- What does the conservation pattern suggest about functional constraints?
- Are there species-specific adaptations visible in the sequence differences?
- How does the conservation level compare to expectations for this gene family?

## Data Sources
List which databases were queried and whether each returned data successfully for each species.

Keep the report factual — only include data returned by the tools. Do not hallucinate sequences, identity scores, or ortholog relationships. If alignment data is unavailable for a species, note "Alignment not performed — sequence unavailable."