seqtree 0.0.1__tar.gz → 0.0.3__tar.gz

{seqtree-0.0.1 → seqtree-0.0.3}/.gitignore

@@ -10,3 +10,4 @@ __pycache__/
 _skbuild/
 docs/_build/
 bench/figures/
+bench/cache/

{seqtree-0.0.1 → seqtree-0.0.3}/CMakeLists.txt

@@ -7,7 +7,9 @@ set(CMAKE_POSITION_INDEPENDENT_CODE ON)
 if(NOT CMAKE_BUILD_TYPE)
   set(CMAKE_BUILD_TYPE Release)
 endif()
-set(CMAKE_CXX_FLAGS_RELEASE "-O3")
+if(NOT MSVC)
+  set(CMAKE_CXX_FLAGS_RELEASE "-O3")
+endif()  # MSVC Release already uses /O2; -O3 is not a valid MSVC flag
 
 option(SEQTREE_TESTS "Build C++ tests" OFF)
 option(SEQTREE_BENCH "Build C++ benchmarks" OFF)
@@ -18,6 +20,8 @@ find_package(Threads REQUIRED)
 add_library(seqtree_core STATIC
   src/codec.cpp
   src/substitution_matrix.cpp
+  src/positional_matrix.cpp
+  src/kmer_index.cpp
   src/trie.cpp
   src/index.cpp
   src/engine_seqtm.cpp
@@ -41,6 +45,10 @@ if(SEQTREE_TESTS)
     tests/cpp/test_matrix.cpp
     tests/cpp/test_trie.cpp
     tests/cpp/test_engines.cpp
+    tests/cpp/test_edge.cpp
+    tests/cpp/test_serialize.cpp
+    tests/cpp/test_positional.cpp
+    tests/cpp/test_kmer_index.cpp
   )
   target_include_directories(seqtree_tests PRIVATE tests/cpp src)
   target_link_libraries(seqtree_tests PRIVATE seqtree_core)

{seqtree-0.0.1 → seqtree-0.0.3}/PKG-INFO

@@ -1,6 +1,6 @@
 Metadata-Version: 2.2
 Name: seqtree
-Version: 0.0.1
+Version: 0.0.3
 Summary: Fast fuzzy search over biological sequences (C++ core, Python bindings)
 Keywords: sequence-search,fuzzy-matching,CDR3,immunology,bioinformatics,trie
 Author-Email: ISALGO laboratory <mikhail.shugay@gmail.com>
@@ -25,10 +25,17 @@ Provides-Extra: docs
 Requires-Dist: sphinx; extra == "docs"
 Requires-Dist: pydata-sphinx-theme; extra == "docs"
 Requires-Dist: nbsphinx; extra == "docs"
+Provides-Extra: control
+Requires-Dist: huggingface_hub; extra == "control"
+Provides-Extra: pmhc
+Requires-Dist: huggingface_hub; extra == "pmhc"
 Description-Content-Type: text/markdown
 
 # seqtree
 
+[![PyPI](https://img.shields.io/pypi/v/seqtree.svg)](https://pypi.org/project/seqtree/)
+[![Python](https://img.shields.io/pypi/pyversions/seqtree.svg)](https://pypi.org/project/seqtree/)
+[![License](https://img.shields.io/pypi/l/seqtree.svg)](LICENSE)
 [![CI](https://github.com/antigenomics/seqtree/actions/workflows/ci.yml/badge.svg)](https://github.com/antigenomics/seqtree/actions/workflows/ci.yml)
 [![Docs](https://github.com/antigenomics/seqtree/actions/workflows/docs.yml/badge.svg)](https://antigenomics.github.io/seqtree/)
 
@@ -49,7 +56,25 @@ Two search engines over one trie:
 `(ref_id, score, n_subs, n_ins, n_dels)`. Downstream libraries map `ref_id` back
 to their own payloads (V gene, MHC, counts) and filter.
 
-## Build
+Beyond search, seqtree ships:
+
+- **Substitution matrices** — built-in `BLOSUM62` and `PAM50`, plus custom matrices via
+  `SubstitutionMatrix.from_similarity` (Gram-distance penalty `s(a,a)+s(b,b)−2·s(a,b)`).
+- **E-values / significance** — calibrate hit counts against a background control repertoire
+  (`load_control` + `evalues`), the TCRNET approach on a finite-sample footing. See the
+  [E-value guide](https://antigenomics.github.io/seqtree/evalue.html).
+
+## Install
+
+```fish
+pip install seqtree       # prebuilt wheels for CPython 3.10–3.13
+```
+
+Prebuilt wheels cover **Linux x86-64**, **macOS arm64 (Apple Silicon)**, and **Windows x86-64**.
+There are **no Intel/x86-64 macOS wheels** — Intel Macs build from source (see below), which just
+needs a C++17 compiler and CMake (pulled in automatically by the build).
+
+## Build from source
 
 ```fish
 bash setup.sh            # repo-local .venv + editable install
@@ -81,6 +106,13 @@ print(aln.aligned_query, aln.aligned_ref, aln.ops)
 
 # batch-vs-batch (auto-indexes the larger set)
 pairs = seqtree.pairwise_batch(query_set, db_set, p, alphabet="aa")
+
+# E-values against a background control repertoire (TCRNET-style significance)
+control = seqtree.load_control("human_trb_aa", size=1_000_000)
+target = seqtree.Index.build(vdjdb_cdr3s, alphabet="aa")
+for q, r in zip(queries, seqtree.evalues(target, control, queries, p)):
+    if r["p_enrichment"] < 1e-3:
+        print(q, r["E"], r["n_target"], r["n_control"])
 ```
 
 ## Tests
@@ -95,10 +127,17 @@ pytest tests/python              # Python tests
 ## Benchmarks
 
 ```fish
-python bench/bench.py                                   # fast tier (real VDJdb data)
-env RUN_BENCHMARK=1 python bench/bench.py --sizes 1000000 --queries 1000000 --threads 16
+python bench/bench_gnuplot.py        # throughput / scaling / matrix / collisions → SVG (needs gnuplot)
+python bench/bench.py                # recall vs ground truth (real VDJdb data)
+python bench/bench_evalue.py         # true E-value benchmark (target vs background control)
+python bench/bench_evalue_matrix.py  # significance across reference/control/query/scope grid
+python bench/bench_epitope.py        # epitope detection-complexity (GIL vs NLV)
 ```
 
+Figures (throughput, scaling, matrix-scoring overhead, collisions, E-value matrix, epitope
+detection) and the full methodology are in the [benchmarks docs](https://antigenomics.github.io/seqtree/benchmarks.html).
+Set `RUN_BENCHMARK=1` for the large tiers.
+
 ## Development
 
 This repo follows **git-flow**:
@@ -107,5 +146,6 @@ This repo follows **git-flow**:
 - `dev` — integration branch for day-to-day work.
 - feature branches branch off `dev` and merge back via PR; releases merge `dev` → `master`.
 
-Roadmap (affine gaps, position-specific matrices, e-value / significance via
-control-set and tf-idf, succinct memory packing) lives in [docs/roadmap.rst](docs/roadmap.rst).
+Roadmap (affine gaps, position-specific matrices, succinct memory packing) lives in
+[docs/roadmap.rst](docs/roadmap.rst). Control-set E-values already ship — see the
+[E-value guide](https://antigenomics.github.io/seqtree/evalue.html).

{seqtree-0.0.1 → seqtree-0.0.3}/README.md

@@ -1,5 +1,8 @@
 # seqtree
 
+[![PyPI](https://img.shields.io/pypi/v/seqtree.svg)](https://pypi.org/project/seqtree/)
+[![Python](https://img.shields.io/pypi/pyversions/seqtree.svg)](https://pypi.org/project/seqtree/)
+[![License](https://img.shields.io/pypi/l/seqtree.svg)](LICENSE)
 [![CI](https://github.com/antigenomics/seqtree/actions/workflows/ci.yml/badge.svg)](https://github.com/antigenomics/seqtree/actions/workflows/ci.yml)
 [![Docs](https://github.com/antigenomics/seqtree/actions/workflows/docs.yml/badge.svg)](https://antigenomics.github.io/seqtree/)
 
@@ -20,7 +23,25 @@ Two search engines over one trie:
 `(ref_id, score, n_subs, n_ins, n_dels)`. Downstream libraries map `ref_id` back
 to their own payloads (V gene, MHC, counts) and filter.
 
-## Build
+Beyond search, seqtree ships:
+
+- **Substitution matrices** — built-in `BLOSUM62` and `PAM50`, plus custom matrices via
+  `SubstitutionMatrix.from_similarity` (Gram-distance penalty `s(a,a)+s(b,b)−2·s(a,b)`).
+- **E-values / significance** — calibrate hit counts against a background control repertoire
+  (`load_control` + `evalues`), the TCRNET approach on a finite-sample footing. See the
+  [E-value guide](https://antigenomics.github.io/seqtree/evalue.html).
+
+## Install
+
+```fish
+pip install seqtree       # prebuilt wheels for CPython 3.10–3.13
+```
+
+Prebuilt wheels cover **Linux x86-64**, **macOS arm64 (Apple Silicon)**, and **Windows x86-64**.
+There are **no Intel/x86-64 macOS wheels** — Intel Macs build from source (see below), which just
+needs a C++17 compiler and CMake (pulled in automatically by the build).
+
+## Build from source
 
 ```fish
 bash setup.sh            # repo-local .venv + editable install
@@ -52,6 +73,13 @@ print(aln.aligned_query, aln.aligned_ref, aln.ops)
 
 # batch-vs-batch (auto-indexes the larger set)
 pairs = seqtree.pairwise_batch(query_set, db_set, p, alphabet="aa")
+
+# E-values against a background control repertoire (TCRNET-style significance)
+control = seqtree.load_control("human_trb_aa", size=1_000_000)
+target = seqtree.Index.build(vdjdb_cdr3s, alphabet="aa")
+for q, r in zip(queries, seqtree.evalues(target, control, queries, p)):
+    if r["p_enrichment"] < 1e-3:
+        print(q, r["E"], r["n_target"], r["n_control"])
 ```
 
 ## Tests
@@ -66,10 +94,17 @@ pytest tests/python              # Python tests
 ## Benchmarks
 
 ```fish
-python bench/bench.py                                   # fast tier (real VDJdb data)
-env RUN_BENCHMARK=1 python bench/bench.py --sizes 1000000 --queries 1000000 --threads 16
+python bench/bench_gnuplot.py        # throughput / scaling / matrix / collisions → SVG (needs gnuplot)
+python bench/bench.py                # recall vs ground truth (real VDJdb data)
+python bench/bench_evalue.py         # true E-value benchmark (target vs background control)
+python bench/bench_evalue_matrix.py  # significance across reference/control/query/scope grid
+python bench/bench_epitope.py        # epitope detection-complexity (GIL vs NLV)
 ```
 
+Figures (throughput, scaling, matrix-scoring overhead, collisions, E-value matrix, epitope
+detection) and the full methodology are in the [benchmarks docs](https://antigenomics.github.io/seqtree/benchmarks.html).
+Set `RUN_BENCHMARK=1` for the large tiers.
+
 ## Development
 
 This repo follows **git-flow**:
@@ -78,5 +113,6 @@ This repo follows **git-flow**:
 - `dev` — integration branch for day-to-day work.
 - feature branches branch off `dev` and merge back via PR; releases merge `dev` → `master`.
 
-Roadmap (affine gaps, position-specific matrices, e-value / significance via
-control-set and tf-idf, succinct memory packing) lives in [docs/roadmap.rst](docs/roadmap.rst).
+Roadmap (affine gaps, position-specific matrices, succinct memory packing) lives in
+[docs/roadmap.rst](docs/roadmap.rst). Control-set E-values already ship — see the
+[E-value guide](https://antigenomics.github.io/seqtree/evalue.html).

seqtree-0.0.3/ROADMAP.md

@@ -0,0 +1,172 @@
+# Downstream wrappers roadmap: `vdjmatch` and `mhcmatch`
+
+**Status:** living draft. Owner: @mikessh. Extend freely — sections marked _(TBD: owner)_ await
+more detail.
+
+**Purpose.** `seqtree` is the shared substrate — a fast, payload-agnostic fuzzy-search core (C++ +
+Python) with a control-calibrated E-value theory (see `appendix/evalue.tex`). It deliberately stops
+at the reference-implementation level: the *applied* tools — `vdjmatch` (TCR antigen specificity) and
+`mhcmatch` (peptide–MHC) — are separate packages built on top of it. This file is the contract
+between them, written so an agent developing either package can pick it up cold: it states what
+`seqtree` already provides, where each wrapper plugs in, and which design decisions are still open.
+
+**How to use this doc (for agents).** Before implementing a feature in `vdjmatch`/`mhcmatch`:
+1. Check **§1 Substrate** for the `seqtree` primitive that already covers it — do not reimplement
+   search, E-values, anchor masking, or k-mer indexing.
+2. Read the matching subsection in **§2** (vdjmatch) or **§3** (mhcmatch) for the intended design and
+   the relevant `appendix/evalue.tex` section.
+3. Treat the math in the appendix as the spec; treat formulas here marked _(design)_ as direction,
+   not final — confirm with the owner before committing to one.
+
+---
+
+## 1. Substrate: what `seqtree` provides
+
+| Capability | Module / symbol | Notes |
+|---|---|---|
+| Fuzzy fixed-length search | `seqtree.Index`, engines `seqtm` / `seqtrie` | per-type edit caps + Hamming fast path; or banded DP |
+| Local / best-window mode | `Mode::Local` (C++) | class-II register, general local match |
+| Substitution scoring | `SubstitutionMatrix` (Gram → squared-distance penalty `s_aa+s_bb−2·s_ab`) | payload-agnostic |
+| Per-position scoring | `PositionalMatrix` (`penalty(pos,a,b)` = base × per-position weight; weight 0 = free/anchor) | the hook for PSSMs and anchor masking |
+| k-mer seed index | `KmerIndex` (C++): unique-k-mer trie + CSR postings + per-peptide allele tag; `seed_and_gather` (GIL-released, parallel) | million-scale candidate generation |
+| Control-calibrated E-values | `seqtree.evalues`, `seqtree.load_control` | `Ê = (N/M)·n_C`, Poisson tail, `exclude_exact` |
+| Anchor / layout model | `seqtree.layout`: `AnchorSpec`, `DEFAULTS`, `mask_anchors`, `kmers`, `presentation_features`, `weight_profile` | parametrized anchors; class-II register trick |
+| pMHC homology + reverse | `seqtree.pmhc`: `PMHCStore`, `search_homologs`, `assign_allele`, `find_mimics`, `build_kmer_index` | reference impl; mhcmatch productionizes |
+| Presentation-aware E-values | `seqtree.pmhc_evalue.homolog_evalue` | per-allele null |
+
+**E-value theory** lives in `appendix/evalue.tex`: the empirical-control null (§Setup, §Null), the
+Poisson/Chen–Stein bound (§Poisson), multiple testing (§E-value), the closest-hit Gumbel law
+(§Gumbel), Karlin–Altschul as the i.i.d. special case (§KA), the pMHC presentation-aware extension
+(§Epitopes, §Reverse problem), and elementary applications — UMI/barcode birthday-collision and
+CDR3-nt error clustering (§Related applications).
+
+**Datasets.** `isalgo/pmhc_data` ships two tiers (see `appendix` Table "Scope of the two pmhc_data
+tiers"): **full** (every IEDB-positive epitope–allele assay) and **shortlist** (epitope–allele pairs
+with ≥2 supporting publications). `mhcmatch` should expose tier choice; the benchmark uses full.
+TCR side: VDJdb (specificity-labelled) + `isalgo/airr_control` (matched control repertoire).
+
+---
+
+## 2. `vdjmatch` — TCR antigen-specificity
+
+**Goal.** Given a query TCR (CDR3, optionally V/J, optionally paired α/β), score its similarity to
+known antigen-specific TCRs and return a control-calibrated E-value per candidate epitope —
+generalizing TCRNET-style neighbour counting (appendix §Intro) to a usable annotation tool.
+
+### 2.1 Train / test / validation splits
+- **Split by epitope, not by sequence.** Held-out *epitopes* test generalization to unseen
+  specificities; held-out *sequences within an epitope* test within-specificity recall. Never let the
+  same clonotype leak across splits (dedup to unique clonotypes first — appendix Prop. on collapse).
+- **Three-way:** train (fit substitution/positional weights, §2.2), validation (tune scope/budget and
+  E-value thresholds), test (report ROC/PR per epitope, as the MHC-guess benchmark does per allele).
+- **Null/control** is independent of the split: `airr_control` supplies the background `P₀`; size it
+  per appendix §"How large must the control be?".
+- _(TBD: owner)_ exact epitope-level CV scheme, minimum cluster size, negative sampling.
+
+### 2.2 Custom substitution matrices (epitope–paratope interaction-aware)
+- **Hook:** `seqtree.PositionalMatrix` (per-position `penalty(pos,a,b)`) and/or a bespoke
+  `SubstitutionMatrix`. seqtree already wires `PositionalMatrix` into the seqtm Hamming path.
+- **Intent:** replace BLOSUM with a CDR3-position-weighted matrix reflecting which residues actually
+  contact the peptide–MHC (paratope), learned from structural contacts or from specificity data
+  (residues whose substitution most changes specificity get the most weight; framework positions →
+  weight 0). Mirrors how `layout.weight_profile` builds anchor/TCR-facing weights for pMHC.
+- _(TBD: owner)_ source of contact statistics (structures vs. learned), per-V-gene vs. global matrix.
+
+### 2.3 Single-chain E-value (have today)
+- Per chain (β, or α), this is exactly `seqtree.evalues`: count neighbours of the query among the
+  epitope-specific set vs. the control, report `Ê` and `p_enrich`. No new theory needed.
+
+### 2.4 Paired α/β E-value (both chains known)
+- _(design)_ Under chain independence in the null, the **joint** null ball-mass factorizes:
+  `π₀^{αβ} ≈ π₀^α · π₀^β`, so the paired intensity is `λ_αβ = N · π₀^α π₀^β` and the paired enrichment
+  is a Poisson tail on the count of references matching **both** chains within budget. Equivalent to
+  Fisher-combining the per-chain `p_enrich` when independence holds; the appendix `b₂` co-occupancy
+  term measures the dependence to correct for. Implement as a joint `seed_and_gather` keyed on a
+  paired peptide id.
+- This is strictly more specific than either chain alone (joint null mass is tiny) → far smaller
+  E-values for true pairs.
+
+### 2.5 Paired estimate for a single chain (rarity of the unknown chain)
+- _(design)_ When only one chain (say β) is observed, marginalize the paired E-value over the unknown
+  α: weight the single-chain evidence by the **rarity** of the partner that would complete a known
+  pair — a generation-probability / abundance prior on α (`Pgen`, appendix §thymic/selection). A β
+  matching a rare-α-paired reference is more informative than one matching a common-α pairing. Yields
+  a "paired-equivalent" E-value from one chain without observing the other.
+- _(TBD: owner)_ the exact prior (OLGA/Murugan `Pgen` vs. empirical α-abundance), and calibration.
+
+### 2.6 API sketch _(non-binding)_
+```python
+vm = vdjmatch.Annotator.from_vdjdb(chains=("beta",), matrix=paratope_matrix, control=airr_control)
+hits = vm.annotate(cdr3b="CASS...", v="TRBV...", scope=2)          # -> [(epitope, Ê, p_enrich), ...]
+hits = vm.annotate_paired(cdr3a=..., cdr3b=...)                    # §2.4
+hits = vm.annotate(cdr3b=..., partner_prior="pgen")               # §2.5
+```
+
+---
+
+## 3. `mhcmatch` — peptide–MHC
+
+**Goal.** Productionize the `seqtree.pmhc` reference layer: epitope homology / cross-reactivity,
+molecular mimicry, allele guessing, and non-binder filtering — with tuned thresholds and the
+additions below.
+
+### 3.1 Reuse from seqtree (have today)
+- Homology / mimicry: `search_homologs`, `find_mimics` (anchor-masked TCR-facing k-mers; per-allele
+  presentation-aware E-values via `pmhc_evalue.homolog_evalue`). Positive control: the Dolton et al.
+  A\*02:01 cross-reactive trio.
+- Allele guessing (reverse problem): `assign_allele` + the vote-fraction ranking / register trick
+  validated in `bench/bench_mhc_guess.py` (appendix §Reverse problem). ROC-AUC 0.90–0.98.
+- **Non-binder filter** (appendix §Reverse problem, "Filtering non-binders"): _binds no MHC_ →
+  best-over-panel E-value high / no allele scores above background; _doesn't bind allele a_ →
+  per-allele `E_a > α`. mhcmatch exposes both thresholds.
+- Tier choice (full vs shortlist, §1 Datasets).
+
+### 3.2 Motif logos
+- For each allele (and each class-II core register), render a sequence logo of the anchor / pocket
+  residues from its presented set — the visual counterpart of `presentation_features`. Use a standard
+  information-content logo (bits per position). Class II: build the logo over the register-aligned
+  9-mer cores (the register trick already picks the core), so anchors P1/P4/P6/P9 are columns.
+- _(TBD: owner)_ logo library choice; whether to weight by `n_references` (shortlist confidence).
+
+### 3.3 MHC pseudosequence → clustering & promiscuity
+- **Pseudosequence:** represent each allele by the polymorphic residues that line the peptide-binding
+  groove (the pseudosequence of peptide-contacting positions, as used for per-allele MHC binding
+  prediction by Glynn, Ghersi & Singh, *PNAS* 2025, [doi:10.1073/pnas.2405106122](https://doi.org/10.1073/pnas.2405106122)).
+  This turns "allele" from an opaque label into a short sequence the **same seqtree engine** can compare.
+- **Cluster MHCs** by pseudosequence distance (seqtree fuzzy search on the pseudosequence "alphabet"
+  of groove residues) → groups of functionally similar alleles. This is the principled way to express
+  **cross-allele similarity**, which `seqtree.pmhc` deliberately does *not* model (appendix §Impl.
+  limitation: "distinct alleles are distinct nulls"). mhcmatch is where that limitation is lifted.
+- **Promiscuity** (esp. class II — appendix §"Class-II promiscuity"): a peptide presented across a
+  pseudosequence-cluster of alleles is promiscuous; quantify as the spread of its positive alleles
+  over the MHC clustering, and use the cluster to pool nulls for related alleles when data are thin.
+- _(TBD: owner)_ pseudosequence position set per locus (HLA-A/B/C, DR/DQ/DP, mouse H-2), distance
+  metric, cluster cut.
+
+### 3.4 API sketch _(non-binding)_
+```python
+mm = mhcmatch.Store.from_pmhc(tier="shortlist")
+mm.logo("HLA-A*02:01")                       # §3.2
+clusters = mm.cluster_alleles(class_="mhc1")  # §3.3, via pseudosequence
+mm.is_binder("SIINFEKL", allele="H-2Kb", alpha=0.05)   # §3.1 non-binder filter
+mm.promiscuity("PKYVKQNTLKLAT")              # §3.3
+```
+
+---
+
+## 4. Shared conventions
+- **seqtree is upstream and stays generic.** New general-purpose primitives (a learned matrix loader,
+  a logo helper, a pseudosequence comparator) may land in seqtree if reusable; tuned thresholds,
+  predictors, and domain glue stay in the wrappers.
+- **Anchors** are parametrized in `seqtree.layout` (presets per class, overridable) — wrappers pass
+  `AnchorSpec`, they don't hardcode positions.
+- **Citations:** never fabricate. Verify every DOI via a tool before adding it (PubMed/arXiv).
+- **Versioning / gitflow:** feature branch → `dev` → `master`; end commit messages with the
+  `Co-Authored-By` trailer; don't publish to PyPI without an explicit release.
+
+## 5. Pointers
+- E-value theory & all derivations: `appendix/evalue.tex` (compiled `appendix/evalue.pdf`).
+- pMHC usage & limitations: `docs/pmhc.rst`. Benchmarks & figures: `docs/benchmarks.rst`,
+  `bench/bench_mhc_guess.py`.
+- seqtree internal roadmap (PSSM-graded d_TCR, native local align, Flashback build, predictor proteome
+  scans): `docs/roadmap.rst`.

seqtree-0.0.3/appendix/.gitignore

@@ -0,0 +1,10 @@
+# LaTeX build artifacts
+*.aux
+*.bbl
+*.blg
+*.fdb_latexmk
+*.fls
+*.log
+*.out
+*.toc
+# evalue.pdf is committed (linked from the docs); regenerate with `make`.

seqtree-0.0.3/appendix/.latexmkrc

@@ -0,0 +1,2 @@
+# OldStandard OpenType text+math requires lualatex (see Makefile).
+$pdf_mode = 4;

seqtree-0.0.3/appendix/Makefile

@@ -0,0 +1,17 @@
+# Compile the E-value derivation. Requires a TeX distribution (latexmk + lualatex + bibtex)
+# and rsvg-convert (librsvg) to convert the referenced SVG plots to PDF for \includegraphics.
+# lualatex (not pdflatex) is required for the OldStandard OpenType text+math fonts; the
+# compiler is pinned in .latexmkrc ($pdf_mode = 4) so a bare `latexmk` also picks it up.
+FIGS = epitope_detection.pdf evalue_matrix.pdf mhc1_rocpr.pdf mhc2_rocpr.pdf
+
+evalue.pdf: evalue.tex refs.bib $(FIGS)
+	latexmk -lualatex -interaction=nonstopmode -halt-on-error evalue.tex
+
+# Benchmark SVGs (bench/figures) -> PDF for inclusion as figures.
+%.pdf: ../bench/figures/%.svg
+	rsvg-convert -f pdf -o $@ $<
+
+.PHONY: clean
+clean:
+	latexmk -C evalue.tex
+	rm -f $(FIGS)