tooluniverse-comparative-genomics

Identifies orthologs and compares gene function across species using Ensembl, UniProt, and Monarch.

1.7k|254|Updated Mar 3, 2025
One-click install
npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-comparative-genomics
Or copy as Structured Prompt for Agent
Please help me install this Agent Skill.
Skill: tooluniverse-comparative-genomics
Source: https://github.com/mims-harvard/ToolUniverse/tree/main/plugins/tooluniverse/skills/tooluniverse-comparative-genomics
Command: npx skills add https://github.com/mims-harvard/ToolUniverse --skill tooluniverse-comparative-genomics

SYSTEM DOCUMENTATION & REQUIREMENTS

💡 This Skill includes scripts (resource) components.

What problem does it solve?

Determining whether a gene has an equivalent in another species—and whether that equivalent performs the same function—requires querying many disconnected databases (Ensembl Compara, NCBI, UniProt, Monarch, OpenTargets) and interpreting ortholog relationships, conservation metrics, and phenotype data. This Skill orchestrates that entire cross-species comparison workflow so researchers get a verified, database-grounded answer instead of guessing from memory.

Core Features & Use Cases

  • Ortholog Discovery & Gene Trees: Find 1:1, 1:many, and many:many orthologs via Ensembl Compara and OpenTargets, then inspect gene trees for duplication and speciation events.
  • Conservation & Selection Analysis: Retrieve coding sequences and compute dN/dS ratios (Nei-Gojobori method) to distinguish purifying selection, positive selection, and relaxed constraint.
  • Functional & Phenotype Comparison: Compare GO annotations across species via UniProt and bridge human disease phenotypes to model organism phenotypes via Monarch.
  • Use Case: A researcher studying a human disease gene asks whether mouse is a good model. The Skill finds the mouse ortholog, confirms a 1:1 relationship, compares GO terms, checks that mouse phenotypes in Monarch recapitulate the human disease, and reports whether the model is well-supported.

Quick Start

Find the mouse ortholog of human TP53, compare its functional annotations, and assess whether mouse phenotypes recapitulate the human disease.

Frequently Asked Questions about tooluniverse-comparative-genomics

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I find the mouse ortholog of a human gene?

Use EnsemblCompara_get_orthologues with the gene symbol, species set to human, and target_species set to mouse. It returns the ortholog with its homology type (one2one, one2many, many2many) and taxonomy divergence level.

How to compute dN/dS ratio between two orthologous genes?

Retrieve the coding sequences of both orthologs, codon-align them, then run the bundled dnds.py script or the Sequence_dn_ds tool. It implements the Nei-Gojobori 1986 estimator with Jukes-Cantor correction and returns dN, dS, dN/dS, and an interpretation.

What does a 1:many ortholog relationship mean for functional analysis?

A 1:many relationship means the target species duplicated the gene, and copies may have subfunctionalized or neofunctionalized. Do not assume both copies retain the full ancestral function; analyze each paralog individually.

Why does Ensembl Compara find no ortholog for my gene?

The gene may be lineage-specific, highly divergent, or missing due to a fragmented reference assembly. Check assembly quality with NCBIDatasets tools, try ensembl_get_homology or OpenTargets homologues, and use BLAST only as a last resort since it is slow.

Can I compare GO annotations between human and mouse genes?

Yes, retrieve GO terms for each species via UniProt and group them by Biological Process, Molecular Function, and Cellular Component. Focus conservation claims on shared terms, since missing annotations often reflect annotation bias rather than true divergence.

What are the limitations of cross-species ortholog analysis?

Ensembl Compara covers vertebrates best, with limited invertebrate and plant coverage. Monarch phenotype data is richest for mouse and zebrafish, UniProt GO annotations favor well-studied organisms, and BLAST protein searches can take 5-30 minutes.