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| # BenchRep-T: immuneML-ready AIRR export | |
| This folder contains every BenchRep-T repertoire in AIRR Rearrangement format. It also has metadata files, the benchmark's fixed fold splits, and runnable specifications for [immuneML](https://github.com/uio-bmi/immuneML). | |
| The specimens and rows are the same as in the native files under `Mal-ID/` and `immunoSEQ/`. Only the columns differ: they are mapped onto one shared AIRR schema, and junctions are rebuilt where they can be checked. | |
| - **Source:** built from dataset revision `165c55149366eadfef1507240aa8c0c60d391fbb` with `utils/immuneml_export.py` and `utils/immuneml_tasks.py` from [github.com/boyd-lab/BenchRep-T](https://github.com/boyd-lab/BenchRep-T). | |
| - **Tested with:** immuneML 3.0.27 (with pandas 2.3.3) and the `airr` 2.0.0 schema validator. See [Verification](#verification). | |
| ## Quick start | |
| ```bash | |
| pip install "immuneML==3.0.27" "pandas<3" | |
| ``` | |
| ```python | |
| # Download one cohort with its task files and spec (here: rheumatoid arthritis) | |
| from huggingface_hub import snapshot_download | |
| snapshot_download( | |
| "lordim/BenchRep-T", repo_type="dataset", local_dir="BenchRep-T", | |
| allow_patterns=["immuneML/immunoSEQ/Savola_RA/*", "immuneML/tasks/ra/*", | |
| "immuneML/specs/ra.yaml"], | |
| ) | |
| ``` | |
| From the BenchRep-T code repository, the same download is `python -m utils.huggingface_data --layout immuneml --cohort ra --output-dir BenchRep-T`. | |
| ```bash | |
| cd BenchRep-T # specs use paths relative to this directory | |
| immune-ml immuneML/specs/ra.yaml results/ra | |
| ``` | |
| > **Use pandas 2 with immuneML 3.0.27.** immuneML declares `pandas>=2.1.0`, so a plain `pip install immuneML` currently installs pandas 3. With pandas 3, immuneML 3.0.27 fails to import AIRR files whose text columns are only partly filled, such as Mal-ID's `d_call`. immuneML's own lock file pins pandas 2.1.1. | |
| ## Layout | |
| ``` | |
| immuneML/ | |
| ├── README.md # this file | |
| ├── MANIFEST.tsv # every file: sha256, size; repertoires also: source file, source sha256, rows | |
| ├── export_report.json # per-cohort row counts and junction statistics | |
| ├── Mal-ID/ metadata.csv + repertoires/ 550 specimens | |
| ├── immunoSEQ/ | |
| │ ├── Savola_RA/ metadata.csv + repertoires/ 91 | |
| │ ├── Musvosvi_TB/ metadata.csv + repertoires/ 140 | |
| │ ├── Rawat_T1D/ metadata.csv + repertoires/ 614 | |
| │ ├── Mitchell_T1D/ metadata.csv + repertoires/ 196 | |
| │ └── Emerson_CMV/ metadata.csv + repertoires/ 761 | |
| ├── tasks/<task>/ metadata.csv, fold{0,1,2}_train.csv, fold{0,1,2}_test.csv | |
| └── specs/<task>.yaml one immuneML specification per task | |
| ``` | |
| Repertoire file names are the same as in the native folders. `MANIFEST.tsv` maps every exported repertoire to its native source file and that file's checksum. | |
| ## Repertoire files | |
| Each repertoire file is a gzipped, tab-separated AIRR Rearrangement file. It has one row for each row of the native file, in the same order: no rows are added, removed or merged. Every file has the same 20 columns, including all 14 fields that AIRR requires: | |
| | Column | Mal-ID | immunoSEQ cohorts (Savola, Musvosvi, Rawat, Mitchell, Emerson) | | |
| |---|---|---| | |
| | `sequence_id` | native `sequence_id` | generated as `<specimen_label>\|<row number>`, with rows numbered from 0 | | |
| | `sequence` | native read, uppercased | native rearrangement `sequence` (identical to Adaptive's `nucleotide`) | | |
| | `rev_comp` | `F` (every native `strand` is `+`) | `F` | | |
| | `productive`, `vj_in_frame` | native `t`/`f` written as `T`/`F` | `T`/`T` (native files keep only Adaptive `sequenceStatus == "In"`) | | |
| | `stop_codon` | native `t`/`f` written as `T`/`F` | empty: the Adaptive exports carry no stop-codon flag | | |
| | `locus` | `TRB` (native `TCRB`) | `TRB` | | |
| | `v_call`, `j_call` | native, with alleles (e.g. `TRBV12-3*01`) | native, gene level (e.g. `TRBV12-3`) | | |
| | `d_call` | native | empty (BenchRep-T doesn't harmonize Adaptive D calls) | | |
| | `sequence_alignment`, `germline_alignment`, `v_cigar`, `d_cigar`, `j_cigar` | empty (full IgBLAST fields stay in `Mal-ID/repertoires`) | empty | | |
| | `junction`, `junction_aa` | rebuilt; see below | rebuilt; see below | | |
| | `cdr3_aa` | native `cdr3_aa`, unchanged | native `cdr3_aa`, unchanged | | |
| | `duplicate_count` | empty: Mal-ID files have no count column | native `num_reads` (= Adaptive `count (templates/reads)`); empty where Adaptive gives none or `-1` | | |
| | `repertoire_id` | specimen label | specimen label | | |
| ### `cdr3_aa` and `junction_aa` | |
| These follow IMGT definitions: | |
| - The **junction** runs from the conserved cysteine (2nd-CYS, position 104) to the conserved phenylalanine or tryptophan (J-PHE/J-TRP, position 118), both included. | |
| - The **CDR3** is the junction without those two anchor residues (positions 105–117). | |
| **`cdr3_aa` is the BenchRep-T benchmark sequence.** It is copied from the native files unchanged, and every method in the paper uses it. It is also immuneML's default analysis region (`region_type: IMGT_CDR3`), so the specs analyse exactly the sequences the benchmark used. | |
| **`junction` and `junction_aa` are new.** The native files don't have them; Mal-ID's columns exist but are empty. They are rebuilt from nucleotide data. A candidate junction is kept only if it passes every check: | |
| 1. its length is 3 × (length of `cdr3_aa` + 2); | |
| 2. it contains only A, C, G and T; | |
| 3. it translates without a stop codon; | |
| 4. its translation without the first and last residue equals `cdr3_aa`; | |
| 5. it occurs in `sequence`. | |
| If no candidate passes, both columns are left empty and the row is still exported. Anchor residues are not required to be C and F/W; the table below reports how often they are. | |
| How candidates are found: | |
| - **Mal-ID:** take the last codon of IgBLAST's `fwr3`, then `cdr3`, then the first codon of `fwr4`, after removing alignment gaps (`-`) and uppercasing. | |
| - **Savola, Musvosvi, Mitchell:** take Adaptive's annotated window, `nucleotide[vIndex : vIndex + cdr3Length]`, which Adaptive defines to span the junction. If the window is unusable, fall back to the search below. | |
| - **Rawat, Emerson** (no position columns): translate `sequence` in all three reading frames, find `cdr3_aa`, and take one codon on each side. If more than one valid candidate is found, keep the one with C…F/W anchors. If that still leaves more than one, the junction is left empty (`ambiguous`). | |
| | Cohort | Rows | Junction rebuilt | Anchors C…F/W¹ | Not rebuilt (reason) | | |
| |---|---:|---:|---:|---| | |
| | Mal-ID | 71,302,390 | 99.778% | 99.60% | 146,897 nucleotide CDR3 doesn't translate to `cdr3_aa`; 11,577 length; 134 stop codon | | |
| | Savola_RA | 1,079,493 | 99.9997% | 99.28% | 3 length | | |
| | Musvosvi_TB | 13,963,315 | 99.9998% | 99.34% | 21 length | | |
| | Rawat_T1D | 55,538,654 | 99.9994% | 99.50% | 341 ambiguous | | |
| | Mitchell_T1D | 26,298,037 | 99.9998% | 99.56% | 42 length | | |
| | Emerson_CMV | 119,423,488 | 99.998% | 99.45% | 2,534 ambiguous; 15 stop codon | | |
| ¹ Share of rebuilt junctions that start with C and end with F or W. | |
| A "length" rejection means the annotated window's length doesn't match `cdr3_aa`, and the frame search found no valid alternative. Per-method and per-reason counts are in `export_report.json`. | |
| Using junctions in immuneML: | |
| - With `region_type: IMGT_JUNCTION`, immuneML analyses `junction_aa` and drops the rows without a junction (0.22% of Mal-ID rows, a handful elsewhere). Every other row is kept. | |
| - immuneML 3.0.27 stores empty `junction`/`junction_aa` cells internally as the text `NAN`. Under IMGT_JUNCTION, only its default illegal-character check removes those rows. Don't combine `region_type: IMGT_JUNCTION` with `import_illegal_characters: true`. | |
| **There is no nucleotide `cdr3` column, on purpose.** | |
| - It would only repeat `junction[3:-3]`. | |
| - immuneML 3.0.27 turns empty cells of a partly filled `cdr3` column into `NAN`, then silently drops those rows as containing illegal characters, even under the default IMGT_CDR3 analysis. | |
| - Without the column, immuneML derives `cdr3` from `junction` itself, and keeps every row. | |
| ### Other conversion notes | |
| - **Counts.** BenchRep-T methods weight every row equally and never read counts; the example specs do the same (`reads: unique`). `duplicate_count` is provided for other analyses. | |
| - immuneML reads an empty `duplicate_count` as `-1`. | |
| - It is empty for all Mal-ID rows, and for 8,313,647 Emerson rows (7.0%) in 77 of the 761 Emerson files, where Adaptive reported no template count. | |
| - Mal-ID rows are kept as published, so several rows can share a clone or CDR3. | |
| - **V/J gene names.** Mal-ID calls keep alleles; the immunoSEQ calls are gene level, with V genes that BenchRep-T treats as indistinguishable already collapsed. Before comparing genes across cohorts, strip alleles (`TRBV7-8*01` → `TRBV7-8`) and collapse IMGT singleton names as `utils/gene_harmonization.py::canonicalize_gene` does. The example specs use `cdr3_aa` only. | |
| - **Rows that immuneML would filter.** | |
| - The native files are already filtered to productive rearrangements with standard-amino-acid `cdr3_aa`. | |
| - With the default import settings (`import_productive: true`, `import_illegal_characters: false`), immuneML 3.0.27 keeps every row; this was checked on all cohorts (see Verification). | |
| ## Metadata files | |
| `<cohort>/metadata.csv` is comma-separated (immuneML doesn't read tab-separated metadata) and has one row per specimen: | |
| | Column | Content | | |
| |---|---| | |
| | `filename` | repertoire file name, resolved against `<cohort>/repertoires/` | | |
| | `subject_id` | specimen label. immuneML's manual splits match on `subject_id` and require it to be unique, so it identifies the specimen, not the person | | |
| | `identifier` | `<cohort key>__<specimen label>`, unique across all cohorts | | |
| | `participant_label` | the person: specimens of one participant share it | | |
| | `disease` | the native label, unchanged (e.g. `Healthy/Background`, `Healthy`, `Controller`) | | |
| | `fold` | BenchRep-T's fixed outer fold, 0–2 | | |
| | `age`, `sex`, `ancestry` | where the native metadata has them: Mal-ID and Emerson have all three; Rawat and Mitchell have age and sex | | |
| immuneML treats every column except `filename`, `subject_id` and `identifier` as a label. | |
| These files keep only the fields above. The full native metadata, including HLA, autoantibody and sequencing statistics, stays in `<cohort>/metadata.tsv` outside this folder. Two fields are deliberately left out here: | |
| - Rawat's exact specimen dates; | |
| - Mitchell's `ancestry`, a cohort-level constant set during conversion (see DATASHEET.md). | |
| ## Tasks and folds | |
| Each task folder lists only the task's two classes. Filenames are relative to `immuneML/`, so one dataset can span cohorts. | |
| For each fold k: | |
| - `fold{k}_test.csv` holds that fold's specimens; | |
| - `fold{k}_train.csv` holds the other two folds. | |
| This is exactly how the BenchRep-T evaluators split, and their per-fold predictions are pooled for the reported metrics. immuneML's `k_fold` and `stratified_k_fold` splits don't reproduce these folds: they ignore participants and draw new folds. | |
| | Task | Cohort(s) | Positive class | Negative class | Specimens | Test fold 0 / 1 / 2 | | |
| |---|---|---|---|---:|---| | |
| | `malid-hiv` | Mal-ID | `HIV` | `Healthy/Background` | 295 | 99 / 99 / 97 | | |
| | `malid-t1d` | Mal-ID | `T1D` | `Healthy/Background` | 293 | 98 / 100 / 95 | | |
| | `malid-lupus` | Mal-ID | `Lupus` | `Healthy/Background` | 261 | 88 / 87 / 86 | | |
| | `malid-covid19` | Mal-ID | `Covid19` | `Healthy/Background` | 255 | 85 / 86 / 84 | | |
| | `malid-influenza` | Mal-ID | `Influenza` | `Healthy/Background` | 234 | 78 / 78 / 78 | | |
| | `mitchell-t1d` | Mitchell_T1D | `T1D` | `Healthy/Background` | 196 | 65 / 66 / 65 | | |
| | `t1d-pooled` | Mal-ID + Mitchell_T1D | `T1D` | `Healthy/Background` | 489 | 163 / 166 / 160 | | |
| | `rawat-t1d` | Rawat_T1D | `T1D` | `Healthy/Background` | 614 | 205 / 205 / 204 | | |
| | `tb-progression` | Musvosvi_TB | `Progressor` | `Controller` | 140 | 47 / 48 / 45 | | |
| | `ra` | Savola_RA | `Rheumatoid Arthritis` | `Healthy` | 91 | 30 / 33 / 28 | | |
| | `cmv` | Emerson_CMV | `CMV` | `Healthy/Background` | 761 | 321 / 320 / 120 | | |
| Notes on the folds: | |
| - **Shared controls.** The five Mal-ID tasks share the same 197 healthy controls. | |
| - **Pooled T1D.** `t1d-pooled` adds a `source_cohort` column. It keeps only the demographic columns both cohorts have (age, sex). | |
| - **Emerson.** Fold 2 is the independent validation cohort (cohort 2, 120 specimens); folds 0 and 1 split the discovery cohort. The paper's CMV results are fold 2. | |
| - **Rawat.** The paper's Rawat results are fold 2 (204 specimens). | |
| - **RA.** All 91 specimens are included. The paper's 90-specimen RA comparison is a bootstrap subset that leaves out `RA6-SF`; that is not an exclusion from the dataset. Participant RA6 has three specimens, all in fold 1. | |
| - **TB folds are not fully participant-grouped.** Three controllers have specimens in more than one fold: `07-0177` (folds 0, 1, 2), `07-0202` (0, 2) and `04-1104` (0, 2). The export keeps the folds exactly as the benchmark used them. | |
| ## Specifications | |
| `specs/<task>.yaml` imports the task as an AIRR repertoire dataset with `region_type: IMGT_CDR3`. It encodes repertoires as 3-mer frequencies of `cdr3_aa` (`KmerFrequency`, `reads: unique`) and trains a class-balanced `LogisticRegression`. It contains one `TrainMLModel` instruction per fold, each using a manual split on that fold's train and test CSVs. | |
| The specs are runnable examples of the data contract, not the benchmark's methods. Change the encodings and models as you like, but keep the dataset and `manual_config` blocks to stay on the benchmark folds. | |
| Run the specs from the directory that contains `immuneML/`. Mal-ID (71 M rows) and Emerson (119 M rows) are the largest cohorts, so start with a smaller one. | |
| ## Verification | |
| Before publication, the export was checked as follows: | |
| - **Against the native files:** every row of every file was re-read and compared with its native source. Checks: row counts; `cdr3_aa`, `v_call`, `j_call` and counts unchanged; `sequence` changed only by uppercasing; `sequence_id` unique per file; every rebuilt junction re-checked against the rules above. | |
| - **AIRR schema:** all 287,605,377 rows in all 2,352 files pass the `airr` 2.0.0 Rearrangement validator. | |
| - **immuneML import** (3.0.27, pandas 2.3.3), on 10 specimens × 2,000 rows from every cohort and on the full RA cohort: | |
| - the default import keeps every row; | |
| - `cdr3_aa`, `junction_aa`, V/J calls, `sequence_id` and `duplicate_count` survive the round trip; | |
| - immuneML's derived `cdr3` equals `junction[3:-3]`; | |
| - `IMGT_JUNCTION` drops exactly the rows without a junction. | |
| - **TrainMLModel runs:** | |
| - all three folds of `ra.yaml` on the full RA cohort; | |
| - reduced copies of `mitchell-t1d` (numeric specimen IDs) and `t1d-pooled` (two cohorts, `/` in class names); | |
| - in every run, each fold's train/test sizes match the CSVs. | |
| ## Provenance and terms | |
| - **Regenerating:** from the code repository, run `python -m utils.immuneml_export --snapshot <native download> --output-root <dir>`, then `python -m utils.immuneml_tasks --output-root <dir>`. The gzip output has no timestamps or file names in it, so rerunning with the same software reproduces the checksums in `MANIFEST.tsv`. | |
| - **Terms:** this folder is a reformatting of the native BenchRep-T files and carries the same terms and source attributions. See the dataset card and `DATASHEET.md`. | |