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

Project description

GenAIRR

Synthetic Adaptive Immune Receptor Repertoire Generator

PyPI Tests Python License

High-performance BCR and TCR sequence simulation with full ground-truth annotations.
C engine · 23 species · zero mandatory dependencies · cross-platform wheels


Installation

pip install GenAIRR

Pre-built wheels are available for Linux, macOS, and Windows (Python 3.9+). No compiler required.


Quick Start

from GenAIRR import Experiment
from GenAIRR.ops import rate

# Generate 1,000 mutated human heavy-chain sequences
result = Experiment.on("human_igh").mutate(rate(0.02, 0.08)).run(n=1000, seed=42)

# Each record is an AIRR-format dict with full ground truth
rec = result[0]
rec["sequence"]      # full nucleotide sequence
rec["v_call"]        # e.g. "IGHVF10-G50*04"
rec["d_call"]        # e.g. "IGHD2-21*02"
rec["j_call"]        # e.g. "IGHJ4*02"
rec["mutation_rate"]  # e.g. 0.054
rec["productive"]     # True / False

Realistic Sequencing Experiment

from GenAIRR import Experiment
from GenAIRR.ops import (
    with_d_inversion, with_receptor_revision,
    rate, model, with_isotype_rates, with_antigen_selection,
    with_primer_mask, with_umi, with_pcr,
    with_5prime_loss, with_3prime_loss, with_quality_profile,
    with_indels, with_ns,
)

result = (
    Experiment.on("human_igh")

    # V(D)J recombination with biological events
    .recombine(
        with_d_inversion(0.15),
        with_receptor_revision(0.05),
    )

    # Somatic hypermutation with CSR and selection pressure
    .mutate(
        model("s5f"),
        rate(0.01, 0.05),
        with_isotype_rates(),
        with_antigen_selection(0.5),
    )

    # Library preparation
    .prepare(
        with_primer_mask(),
        with_umi(12),
        with_pcr(error_rate=1e-4, cycles=30),
    )

    # Sequencing artifacts
    .sequence(
        with_5prime_loss(min_remove=5, max_remove=30),
        with_3prime_loss(min_remove=5, max_remove=20),
        with_quality_profile(base=0.001, peak=0.02),
    )

    # Post-sequencing noise
    .observe(
        with_indels(prob=0.005),
        with_ns(prob=0.005),
    )

    .run(n=1000, seed=42)
)

Streaming (Memory-Efficient)

from GenAIRR import Experiment
from GenAIRR.ops import rate

sim = Experiment.on("human_igh").mutate(rate(0.05, 0.15)).compile(seed=42)

for record in sim.stream():
    print(record["v_call"])  # one dict at a time, no accumulation
    break                    # infinite iterator — break when done

Export

result.to_csv("repertoire.tsv")          # AIRR TSV
result.to_fasta("repertoire.fasta")      # FASTA
df = result.to_dataframe()               # pandas DataFrame

Output Fields

Every record is a dictionary containing the absolute ground truth of the simulated sequence. Unlike real-world aligners that must infer gene assignments from statistical models and heuristics, GenAIRR knows the exact origin of every nucleotide. The metadata reflects what a hypothetical perfect aligner would report if it could examine the sequence with full knowledge of the rearrangement process — no ambiguity, no probabilistic gene usage priors, no alignment scoring trade-offs.

Field Type Description
sequence str Full nucleotide sequence (post-corruption if artifacts are enabled)
sequence_length int Length of sequence in bases
germline_alignment str Ungapped germline reference aligned to sequence (lowercase = germline, uppercase = mutated, N = non-templated)
V gene
v_call str V allele name
v_sequence_start int Start of the V segment in sequence (0-based)
v_sequence_end int End of the V segment in sequence (exclusive)
v_germline_start int Start position within the V germline allele
v_germline_end int End position within the V germline allele
v_trim_5 int Bases trimmed from the 5' end of V
v_trim_3 int Bases trimmed from the 3' end of V
D gene
d_call str D allele name (empty for light chains / chains without D)
d_sequence_start int Start of the D segment in sequence
d_sequence_end int End of the D segment in sequence
d_germline_start int Start position within the D germline allele
d_germline_end int End position within the D germline allele
d_trim_5 int Bases trimmed from the 5' end of D
d_trim_3 int Bases trimmed from the 3' end of D
J gene
j_call str J allele name
j_sequence_start int Start of the J segment in sequence
j_sequence_end int End of the J segment in sequence
j_germline_start int Start position within the J germline allele
j_germline_end int End position within the J germline allele
j_trim_5 int Bases trimmed from the 5' end of J
j_trim_3 int Bases trimmed from the 3' end of J
Junction
junction_nt str Junction nucleotide sequence (V-anchor to J-anchor inclusive)
junction_aa str Junction amino acid translation
junction_start int Junction start position in sequence
junction_end int Junction end position in sequence
junction_length int Junction length in nucleotides
N/P regions
np1_region str NP1 nucleotide sequence (between V and D, or V and J)
np1_length int NP1 length in bases
np2_region str NP2 nucleotide sequence (between D and J)
np2_length int NP2 length in bases
Somatic hypermutation
mutation_rate float Fraction of positions mutated
n_mutations int Total number of point mutations
mutations str Comma-separated list of mutations (e.g. 13:a>T,30:g>A)
Functionality
productive bool Whether the sequence is productive (in-frame, no stop codons)
vj_in_frame bool Whether V and J segments are in the same reading frame
stop_codon bool Whether the junction contains a stop codon
note str Reason for non-productivity (e.g. VJ out of frame.)
Isotype
c_call str Constant region allele (when CSR is enabled)
Artifact annotations
n_pcr_errors int Number of PCR-introduced errors
pcr_errors str Comma-separated list of PCR error positions and substitutions
n_sequencing_errors int Number of sequencing-introduced errors
sequencing_errors str Comma-separated list of sequencing error positions and substitutions
is_reverse_complement bool Whether the sequence was reverse-complemented
is_contaminant bool Whether the sequence is a contaminant spike-in

All coordinates are 0-based. Gene segment boundaries account for trimming, N/P additions, and any 5'/3' corruption, so they point to the exact positions in the final sequence string.


Supported Species & Chains

GenAIRR ships with 106 built-in configurations covering 23 species (sourced from IMGT and OGRDB).

from GenAIRR import list_configs
print(list_configs())  # all available configs
Species BCR TCR
Human IGH, IGK, IGL TCRA, TCRB, TCRD, TCRG
Mouse IGH, IGK, IGL TCRA, TCRB, TCRD, TCRG
Rat IGH, IGK, IGL
Rabbit IGH, IGK, IGL TCRA, TCRB, TCRD, TCRG
Dog IGH, IGK, IGL TCRA, TCRB, TCRD, TCRG
Cat IGK, IGL TCRA, TCRB, TCRD, TCRG
Rhesus IGH, IGK, IGL TCRA, TCRB, TCRD, TCRG
All 23 species

Alpaca, Cat, Chicken, Cow, Cynomolgus, Dog, Dromedary, Ferret, Goat, Gorilla, Horse, Human, Mouse (generic + C57BL/6J), Pig, Platypus, Rabbit, Rat, Rhesus, Salmon, Sheep, Trout, Zebrafish.

Experiment.on("mouse_igh").run(n=500)
Experiment.on("rabbit_tcrb").run(n=500)
Experiment.on("rhesus_igk").run(n=500)

Key Features

  • C simulation engine — 15,000–30,000 sequences/second end-to-end on a single core
  • Context-aware S5F somatic hypermutation — 5-mer motif-based targeting with empirical substitution profiles
  • Full AIRR-format output — V/D/J calls, germline alignments, junction boundaries, mutation annotations
  • Sequencing artifact simulation — 5'/3' degradation, indels, N-insertions, quality errors, PCR artifacts
  • Biological processes — D-gene inversion, receptor revision, class switch recombination, selection pressure
  • Allele locking — constrain simulation to specific V/D/J alleles
  • Deterministic seeds — fully reproducible results across runs and platforms
  • Zero mandatory dependencies — optional extras for DataConfig building, visualization, and MCP

Reproducibility

# Pass a seed for deterministic, reproducible results
result = Experiment.on("human_igh").run(n=1000, seed=42)

Optional Extras

pip install GenAIRR[all]          # numpy, scipy, graphviz, tqdm, fastmcp
pip install GenAIRR[dataconfig]   # numpy + scipy (custom DataConfig building)
pip install GenAIRR[mcp]          # FastMCP server for AI-assisted analysis

Citing GenAIRR

If GenAIRR is useful in your research, please cite:

Konstantinovsky T, Peres A, Polak P, Yaari G. An unbiased comparison of immunoglobulin sequence aligners. Briefings in Bioinformatics. 2024;25(6):bbae556. doi:10.1093/bib/bbae556


Contributing

Contributions are welcome. See CONTRIBUTING.md for development setup and guidelines.

License

GPL-3.0. See LICENSE.

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