GenAIRR 0.6.1

An advanced immunoglobulin sequence simulation suite for benchmarking alignment models and sequence analysis.

GenAIRR

Adaptive Immune Receptor Repertoire Sequence Simulator
Generate realistic BCR & TCR repertoires with full ground-truth annotations in Python.

---

Why GenAIRR?

Benchmarking sequence aligners, studying somatic hypermutation, or training ML models on immune repertoires requires large, perfectly-annotated datasets — not noisy snippets of real sequencing data.

GenAIRR is a plug-and-play, fully-extensible simulation engine that produces realistic immunoglobulin and TCR sequences while giving you complete ground-truth labels for every position, mutation, and gene segment.

---

Key Features

Category	Highlights
Realistic Simulation	Context-aware S5F mutations, indels, allele-specific trimming, NP-region modelling
Composable Pipelines	Chain together built-in & custom steps into simulation pipelines
Multi-Chain Support	Heavy chain, kappa/lambda light chains, and TCR-beta out of the box
Research-ready Output	Full ground-truth annotations, JSON/pandas export, deterministic seeds
Docs & Tutorials	Step-by-step guides, Jupyter notebooks, API reference

---

Installation

# Python >= 3.9
pip install GenAIRR

---

Quick Start

One-liner

from GenAIRR import simulate, HUMAN_IGH_OGRDB, S5F

result = simulate(HUMAN_IGH_OGRDB, S5F(0.003, 0.25))
print(result.sequence)

CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCGGGGACCCTGTCCCTCACCTGCGCTG...

Generate multiple sequences at once:

results = simulate(HUMAN_IGH_OGRDB, S5F(0.003, 0.25), n=100)

Pipeline (Full Control)

For complete control over the simulation, use the Pipeline API:

from GenAIRR import Pipeline, steps, HUMAN_IGH_OGRDB, S5F

pipeline = Pipeline(
    config=HUMAN_IGH_OGRDB,
    steps=[
        steps.SimulateSequence(S5F(min_mutation_rate=0.003, max_mutation_rate=0.25), productive=True),
        steps.FixVPositionAfterTrimmingIndexAmbiguity(),
        steps.FixDPositionAfterTrimmingIndexAmbiguity(),
        steps.FixJPositionAfterTrimmingIndexAmbiguity(),
        steps.CorrectForVEndCut(),
        steps.CorrectForDTrims(),
        steps.DistillMutationRate(),
    ]
)

sim = pipeline.execute()
print(sim.get_dict())

{
    'sequence': 'CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCG...',
    'v_call': ['IGHVF3-G8*04'],
    'd_call': ['IGHD6-6*01'],
    'j_call': ['IGHJ4*02'],
    'productive': True,
    'mutation_rate': 0.0027,
    'mutations': {142: 'T>C'},
    'v_sequence_start': 0,
    'v_sequence_end': 293,
    'd_sequence_start': 298,
    'd_sequence_end': 316,
    'j_sequence_start': 323,
    'j_sequence_end': 367,
    # ... and more fields
}

Every output includes the full sequence, V/D/J gene calls, mutation positions, region boundaries, and quality metrics — ready for downstream analysis.

---

Examples

Full Heavy-Chain Pipeline

A production-ready pipeline that simulates sequences with biological corrections and sequencing artifacts:

from GenAIRR import Pipeline, steps, HUMAN_IGH_OGRDB, S5F

pipeline = Pipeline(
    config=HUMAN_IGH_OGRDB,
    steps=[
        # Core: generate sequence with somatic hypermutation
        steps.SimulateSequence(S5F(min_mutation_rate=0.003, max_mutation_rate=0.25), productive=True),

        # Correct ground-truth positions after trimming ambiguities
        steps.FixVPositionAfterTrimmingIndexAmbiguity(),
        steps.FixDPositionAfterTrimmingIndexAmbiguity(),
        steps.FixJPositionAfterTrimmingIndexAmbiguity(),
        steps.CorrectForVEndCut(),
        steps.CorrectForDTrims(),

        # Calculate final mutation rate
        steps.DistillMutationRate(),

        # Simulate sequencing artifacts
        steps.CorruptSequenceBeginning(),   # 5' end degradation
        steps.EnforceSequenceLength(),      # read-length limit
        steps.InsertNs(),                   # ambiguous base calls
        steps.ShortDValidation(),           # D-region QC
        steps.InsertIndels(),               # sequencing indels
    ]
)

result = pipeline.execute()

Naive Sequence (No Mutations)

from GenAIRR import Pipeline, steps, HUMAN_IGH_OGRDB, Uniform

pipeline = Pipeline(
    config=HUMAN_IGH_OGRDB,
    steps=[steps.SimulateSequence(Uniform(0, 0), productive=True)]
)
naive_seq = pipeline.execute()

Light Chain

from GenAIRR import Pipeline, steps, HUMAN_IGK_OGRDB, S5F

pipeline = Pipeline(
    config=HUMAN_IGK_OGRDB,  # kappa light chain (no D segment)
    steps=[
        steps.SimulateSequence(S5F(min_mutation_rate=0.02, max_mutation_rate=0.08), productive=True),
        steps.FixVPositionAfterTrimmingIndexAmbiguity(),
        steps.FixJPositionAfterTrimmingIndexAmbiguity(),
        steps.CorrectForVEndCut(),
        steps.DistillMutationRate(),
    ]
)

Custom Allele Combination

from GenAIRR import Pipeline, steps, HUMAN_IGH_OGRDB, S5F

pipeline = Pipeline(
    config=HUMAN_IGH_OGRDB,
    steps=[
        steps.SimulateSequence(
            S5F(0.003, 0.25),
            productive=True,
            specific_v=HUMAN_IGH_OGRDB.v_alleles['IGHVF1-G1'][0],
            specific_d=HUMAN_IGH_OGRDB.d_alleles['IGHD1-1'][0],
            specific_j=HUMAN_IGH_OGRDB.j_alleles['IGHJ1'][0]
        )
    ]
)

Batch Generation

import pandas as pd
from GenAIRR import Pipeline, steps, HUMAN_IGH_OGRDB, S5F

pipeline = Pipeline(
    config=HUMAN_IGH_OGRDB,
    steps=[
        steps.SimulateSequence(S5F(min_mutation_rate=0.003, max_mutation_rate=0.25), productive=True),
        steps.FixVPositionAfterTrimmingIndexAmbiguity(),
        steps.FixDPositionAfterTrimmingIndexAmbiguity(),
        steps.FixJPositionAfterTrimmingIndexAmbiguity(),
        steps.CorrectForVEndCut(),
        steps.CorrectForDTrims(),
        steps.DistillMutationRate(),
    ]
)

# Generate 1000 sequences as a DataFrame
df = pd.DataFrame([pipeline.execute().get_dict() for _ in range(1000)])
df.to_csv('simulated_repertoire.csv', index=False)

---

Mutation Models

Model	Description	When to use
S5F	Context-dependent somatic hypermutation based on empirical 5-mer frequencies	Realistic antibody maturation studies
Uniform	Uniform random mutations	Baselines, ablation experiments
Custom	Implement BaseMutationModel	Your own evolutionary scenarios

from GenAIRR import S5F, Uniform

# Realistic context-aware SHM
s5f = S5F(min_mutation_rate=0.01, max_mutation_rate=0.05)

# Simple uniform mutations
uniform = Uniform(min_mutation_rate=0.01, max_mutation_rate=0.05)

---

Available Data Configurations

Config	Chain	Source
HUMAN_IGH_OGRDB	Heavy chain (BCR)	OGRDB
HUMAN_IGH_EXTENDED	Heavy chain extended	OGRDB
HUMAN_IGK_OGRDB	Kappa light chain	OGRDB
HUMAN_IGL_OGRDB	Lambda light chain	OGRDB
HUMAN_TCRB_IMGT	TCR-beta	IMGT

---

Reproducibility

from GenAIRR import set_seed, get_seed, reset_seed

set_seed(42)         # deterministic results
print(get_seed())    # check current seed
reset_seed()         # back to random

---

Documentation

• Getting Started — Overview and first pipeline
• Step-by-Step Tutorial — Build a pipeline from scratch
• API Reference — All classes, parameters, and defaults
• Migration Guide — Upgrading from older versions
• Biological Context — What biological processes are simulated

---

Roadmap

• Selection-aware mutation model
• Additional germline databases
• Sphinx auto-generated API docs from docstrings

See open issues. Feel something's missing? Open a feature request.

---

Contributing

Contributions are welcome! Please read our contributing guide and check the good first issue label.

---

Citing GenAIRR

If GenAIRR helps your research, please cite:

Konstantinovsky T, Peres A, Polak P, Yaari G.
An unbiased comparison of immunoglobulin sequence aligners.
Briefings in Bioinformatics. 2024 Sep 23; 25(6): bbae556.
https://doi.org/10.1093/bib/bbae556
PMID: 39489605 | PMCID: PMC11531861

---

License

Distributed under the GPL-3.0 License. See LICENSE for details.

---

Acknowledgements

GenAIRR is inspired by and builds upon work from the immunoinformatics community — especially AIRRship.