arda — Antigen Receptor Domain Annotation

Quickstart · Documentation · Commands · Output reference · Benchmarks

arda annotates T and B cell receptor sequences. Give it sequencing reads — bulk RNA-seq, targeted amplicon or single cell — and it returns AIRR Rearrangement records with V/D/J/C gene calls, FR1–FR4 and CDR1–CDR3 coordinates and the junction, plus a clonotype table. One command, no workflow engine, no container.

It works on nucleotide and amino-acid input, on FASTA and FASTQ, across all loci in one pass, for human and mouse (full IG + TR) and for rat, rabbit and rhesus macaque (IG only — IMGT ships no TR reference for those three). It also annotates records with no read behind them — a CDR3 amino acid plus a V and J call, as in a VDJdb row — marking up which residues each germline templates and repairing the junction. D inference from amino-acid junctions is provided by vdjtools, using ARDA markup and germline.

Install

pip install arda-mapper

That is all. The distribution is arda-mapper and imports as arda; binary wheels carry its C++ extensions for CPython 3.10–3.13 on Linux, macOS (arm64) and Windows. The MMseqs2 search binary and the curated germline reference are fetched automatically on first use into ~/.cache/arda — no conda, no manual reference build on Linux and macOS. On Windows, run search workflows with Linux Python inside WSL2; the automatic MMseqs2 downloader targets Linux and macOS. Run arda info to see what got resolved.

For a development checkout, bash setup.sh builds a uv venv, compiles the extensions and fetches IgBLAST and MMseqs2. See the installation guide.

Quick start

Pick the mode that matches your library. The mode name carries that library's speed configuration, so there are no flags to get right:

arda rnaseq   --r1 R1.fq.gz --r2 R2.fq.gz -p SAMPLE -d out/   # bulk / whole-transcriptome
arda amplicon --r1 R1.fq.gz --r2 R2.fq.gz -p SAMPLE -d out/   # targeted RepSeq / 5'RACE
arda cells    asm/PBMC.consensus.fq.gz -p out/PBMC            # single cell, from UMI consensus

rnaseq and amplicon run mapping → assembly → error correction and write:

Single-cell runs assemble molecules per cell before annotation and pairing, writing SAMPLE.contigs.fasta, SAMPLE.contigs.airr.tsv, SAMPLE.chains.tsv and SAMPLE.cells.tsv, plus diagnostics and QC. See the single-cell output reference.

Progress goes to stderr; the output paths, one per line, to stdout.

Already have assembled sequences? Skip the pipeline:

arda annotate -i sequences.fasta -o out.airr.tsv --organism human

Full walkthrough with real output: Quickstart.

Why arda

IgBLAST-quality regions, without IgBLAST at runtime. arda does the expensive work once, offline, building a reference of every in-frame V·J germline scaffold already annotated by IgBLAST. At runtime it maps a query to that reference with MMseqs2 and projects the markup through the alignment in C++. Region concordance with IgBLAST is 98–99.7 % on ~7,300 real GenBank mRNA records across five organisms. IgBLAST is needed only to rebuild the reference.

Precise on bulk RNA-seq. Over 16 datasets where every compared tool ran (5,273 real fragments, Wilson 95 % CIs): recall 0.986 [.982–.989], precision lower bound 0.889 [.881–.897]. Recall ties TRUST4; precision does not — arda's lower bound sits above every competitor's upper bound.

Cheap, not only fast. Mapping holds a flat 300–650 MB at any read depth, which is what lets many samples share a node. On a 100,000-read TRA amplicon arda uses 3.2× less peak memory and 1.4× less CPU than MiXCR, and returns the most clonotypes over the most reads.

It declines rather than guessing. A D call carries the E-value it was accepted on. A junction whose Cys104 anchor is not in the read is not emitted. A germline with no derivable anchor is flagged, not invented. A j_call requires J evidence rather than inheriting it from the scaffold.

Embeddable and scriptable. import arda; arda.annotate_sequences(...) returns AIRR record dicts. The library runs MMseqs2 and manages temporary search files internally. The CLI uses plain files in and out, so it drops into any workflow engine; the same sample sheet drives the CLI, a SLURM array, the Nextflow module and the Snakemake workflow, and a sharded run is byte-identical to a single-node one.

Every figure above is measured. Methods, repetition spread, and what each comparison is and is not entitled to claim: Benchmarks.

Documentation

Start with the tutorial, use a how-to guide for a task, consult reference pages for exact interfaces, and read the explanations for the reasoning behind them.

From Python

import arda

records = arda.annotate_sequences(
    ["GACGTGCAG...", ("clone7", "CAGGTG...")],   # strings or (id, seq) pairs
    seqtype="nt", organism="human",
)

Each record is a dict of AIRR fields — v_call, d_call/d2_call, j_call, c_call/c_class, fwr1–fwr4, cdr1–cdr3 with 1-based closed *_start/*_end and *_aa, junction(_aa), np1–np3, d_support, the per-segment CIGARs, v_mutations/j_mutations, productive, and more. The TSV form passes airr.schema validation.

Reading arda's output — note that quoting is off, both when writing and when reading:

import polars as pl

clones = pl.read_csv("out/SAMPLE.clones.tsv", separator="\t", quote_char=None)
top = (clones.filter(pl.col("locus") == "TRB")
       .with_columns((pl.col("duplicate_count") / pl.col("duplicate_count").sum()).alias("frequency"))
       .sort("duplicate_count", descending=True))

Examples

examples/ is a runnable tour, every artifact derived from real data committed to this repository and regenerated by python examples/regenerate.py: one real mRNA per locus; the two human reads (of 7,341, across five organisms) carrying a tandem D-D; seven VDJdb records covering every junction-repair outcome; and a 1,035-read FASTQ that runs the whole bulk RNA-seq pipeline in about six seconds.

Development

bash setup.sh                                         # uv venv, C++ extensions, IgBLAST, mmseqs
source .venv/bin/activate

python -m pytest tests/unit tests/synthetic tests/realworld -q   # the CI gate
ruff check src/
make -C docs html                                                # zero warnings required

tests/realworld compares against IgBLAST on committed fixtures and runs offline. tests/benchmark is opt-in with RUN_BENCHMARK=1. Install -e '.[test]' before reading a green suite as full coverage — optional extras gate optional suites.

Layout: the package is src/arda/ (cli.py, annotate/, rnaseq/, refbuild/), the four nanobind C++ extensions are src/_markup/, src/_prefilter/, src/_segmap/, src/_denoise/, the committed references are in database/, and integrations/ holds the Nextflow module and Snakemake workflow. Contributor guidance is in AGENTS.md; design records are in project/; planned work is in ROADMAP.md; data provenance is in SOURCES.md; per-release changes are in CHANGELOG.md.

Related tools

arda is part of the antigenomics stack and stays deliberately inside annotation. Repertoire biology — diversity, clonality, rarefaction, overlap, cross-sample clonotype matching — belongs to vdjtools, which takes arda-mapper as a dependency.

License

ISALGO LAB Academic and Non-Commercial Research License v1.0. See LICENSE.