bio-tcr-bcr-analysis-vdjtools-analysis - SKILL.md Agent Skill

name: bio-tcr-bcr-analysis-vdjtools-analysis description: Calculate immune repertoire diversity metrics, compare samples, and track clonal dynamics using VDJtools. Use when analyzing repertoire diversity, finding shared clonotypes, or comparing immune profiles between conditions. tool_type: cli primary_tool: VDJtools measurable_outcome: Execute skill workflow successfully with valid output within 15 minutes. allowed-tools: - read_file - run_shell_command

VDJtools Analysis

Basic Usage

# VDJtools requires Java
java -jar vdjtools.jar <command> [options]

# Or with wrapper script
vdjtools <command> [options]

Calculate Diversity Metrics

# Basic diversity (Shannon, Simpson, Chao1, etc.)
vdjtools CalcDiversityStats \
    -m metadata.txt \
    output_dir/

# Metadata format (tab-separated):
# #file.name    sample.id    condition
# sample1.txt   S1           control
# sample2.txt   S2           treated

Diversity Metrics Explained

Metric	Description	Interpretation
Shannon	Entropy-based diversity	Higher = more diverse
Simpson	Probability two random clones differ	0-1, higher = diverse
InverseSimpson	1/Simpson	Effective number of clones
Chao1	Richness estimator	Total estimated clonotypes
Gini	Inequality coefficient	0=equal, 1=dominated by one
d50	Clones comprising 50% of repertoire	Lower = more oligoclonal

Sample Comparison

# Find overlapping clonotypes
vdjtools OverlapPair \
    -p sample1.txt sample2.txt \
    output_dir/

# Calculate overlap for all pairs
vdjtools CalcPairwiseDistances \
    -m metadata.txt \
    -i aa \
    output_dir/

# Overlap metrics: F2 (frequency-weighted Jaccard), Jaccard, MorisitaHorn

Spectratype Analysis

# CDR3 length distribution (spectratype)
vdjtools CalcSpectratype \
    -m metadata.txt \
    output_dir/

# V/J gene usage
vdjtools CalcSegmentUsage \
    -m metadata.txt \
    output_dir/

Clonal Tracking

# Track clones across timepoints
vdjtools TrackClonotypes \
    -m metadata_timecourse.txt \
    -x time \
    output_dir/

# Identify public clones (shared across individuals)
vdjtools JoinSamples \
    -m metadata.txt \
    -p \
    output_dir/

Input Format

VDJtools accepts MiXCR output or standard format:

# Required columns (tab-separated):
count   frequency   CDR3nt  CDR3aa  V   D   J

# Example:
1500    0.15    TGTGCCAGC...    CASSF...    TRBV5-1*01  TRBD2*01    TRBJ2-7*01

Convert from MiXCR

# Convert MiXCR output to VDJtools format
vdjtools Convert \
    -S mixcr \
    mixcr_clones.txt \
    output.txt

Parse VDJtools Output in Python

import pandas as pd

def load_diversity_stats(filepath):
    '''Load VDJtools diversity statistics'''
    df = pd.read_csv(filepath, sep='\t')
    return df

def load_overlap_matrix(filepath):
    '''Load pairwise overlap matrix'''
    df = pd.read_csv(filepath, sep='\t', index_col=0)
    return df

# Plot diversity across samples
def plot_diversity(stats_df, metric='shannon_wiener_index_mean'):
    import matplotlib.pyplot as plt

    plt.figure(figsize=(10, 6))
    plt.bar(stats_df['sample_id'], stats_df[metric])
    plt.xlabel('Sample')
    plt.ylabel(metric)
    plt.xticks(rotation=45)
    plt.tight_layout()
    plt.savefig('diversity_plot.png')

Related Skills

mixcr-analysis - Generate input clonotype tables
repertoire-visualization - Visualize VDJtools output
immcantation-analysis - BCR-specific phylogenetics