mutation-effect

name	mutation_effect
description	Analyze mutations by comparing wild-type and mutant sequences. Use this skill when: (1) User provides WT and MT sequences, (2) User asks about mutation impact (e.g., "p.R175H"), (3) User wants to compare two sequences, (4) User asks "what's the difference between these sequences".
license	MIT
category	mutation-analysis
tags	["mutation","variant","sequence-comparison","hgvs"]

Mutation Effect Analysis

Compare wild-type and mutant sequences to identify mutations.

When to Use

• User provides WT and MT sequences
• User asks about mutation impact (p.R175H)
• User wants to compare two sequences
• User asks "what's the difference"

Workflow

Step 1: Parse Input

Extract WT and MT sequences from user input:

WT: MEEPQSDPSVEPPLSQETFSDLWKLLPENNVLSPLPSQAMDDLMLSPDDIEQWFTEDPGP
MT: p.R175H

or

WT: ATCG
MT: ATGG

Step 2: Compute Differences

from open_rosalind.skills_v2.mutation import tools

diff = tools.diff(wt="MEEPQ", mt="MEEPQ")
# Returns: {n_differences: 0, positions: [], changes: [], severity: "none"}

diff = tools.diff(wt="MEEPQ", mt="MEEPH")
# Returns: {n_differences: 1, positions: [4], changes: ["Q→H"], severity: "moderate"}

Step 3: Classify Impact

Rule-based classification:

• Charge reversal (K→E, R→D): high
• Hydrophobic→polar (V→S): moderate
• Conservative (I→L): low
• Synonymous: none

Step 4: Return Evidence-Grounded Result

return {
    "annotation": {
        "kind": "mutation",
        "n_differences": 1,
        "severity": "moderate"
    },
    "confidence": 0.75,
    "notes": [],
    "mutation": diff  # Full diff object (evidence)
}

Expected Outputs

Field	Description
n_differences	Number of mutations
positions	List of mutation positions
changes	List of changes (e.g., "Q→H")
severity	Impact level (none/low/moderate/high)
properties	Property changes (charge, hydrophobicity)

Design Principles

1. Tool-first: All data from mutation.diff tool
2. Evidence-grounded: Return full mutation object
3. Traceable: Diff computation logged
4. Fail-safe: Invalid sequences → confidence=0.0

Fallback Strategy

If sequences are identical:

• Return n_differences=0
• severity="none"
• Log to notes