NEWS

---

pepVet 0.99.0

User-visible changes

• Redesigned interactive digest reports with ASCII-safe score profiles, explicit scoring settings and peptide counts, wrapped identifiers, and width-aware enzyme comparisons.
• Preserved resolved scoring metadata through single-protein, comparison, batch, sensitivity, and plotting workflows.
• Restored Windows protein-chunk parallelism through base R socket workers. Unix uses fork workers, and failed chunks on either backend are retried sequentially with a classed warning.

Validation and fixes

• Standardized malformed-input handling across digestion, scoring, evaluation, export, reporting, diagnostics, and plotting. Invalid inputs now fail through package conditions before reaching base R errors.
• Rejected duplicate protein identifiers and duplicate data-frame columns before they can collapse or corrupt downstream results.
• Applied the zero-count digest rule consistently: digests without peptides inside the active length range receive a zero composite score and a Poor verdict.
• Corrected the workflow-preset comparison to apply complete preset settings against an explicit three-protein digest background.
• Distinguished theoretical products, length-valid peptides, combined comparison windows, model score bands, and model-based rankings throughout package-facing documentation.
• Fixed missed-cleavage filtering in peptide-overlap plots when all levels are requested, and validated plot titles and figure dimensions before rendering.
• Corrected weight sensitivity tie handling, corner diagnostics, batch aggregation, and single-result plot semantics. Results now record simulation settings, and batch memory is bounded by a smaller default chunk.

Testing

• Reworked the test suite around public contracts, scientific invariants, classed conditions, metadata, plot semantics, and platform-specific batch execution.
• Added generated-sequence properties and a malformed-input audit covering all 37 exported functions.
• Added fast contract tests for shipped FASTA, tool-comparison, and PeptideAtlas artifacts. Data-generation workflows now run as separate offline audits and fail clearly when required inputs are missing.
• Removed an architecture-dependent threshold collision from the diagnostics ablation oracle so installed-package tests retain the same verdict-flip expectation across BLAS implementations.
• Corrected Windows-specific test assumptions about normalized path separators and avoided reinstalling an already installed package during R CMD check.

Documentation and metadata

• Prepared the package metadata and installation guidance for initial Bioconductor submission.
• Reconciled the README, vignettes, help pages, package metadata, and generated site with the current scoring and validation contracts.
• Removed the redundant custom package citation because pepVet does not yet have an associated publication DOI. Installed citations now come from DESCRIPTION metadata.
• Described the scoring weights as documented expert priors because their original derivation record is not retained. The numeric weights are unchanged.

Release infrastructure

• Added Linux coverage reporting with a 90 percent floor, retained coverage artifacts, and Codecov upload support.
• Added pkgdown builds for pull requests and GitHub Pages deployment from main, with bounded build stages and cancellation of obsolete runs.
• Added a source-package artifact build alongside parallel release-R checks on Linux, macOS, and Windows, with unfinished checks cancelled after the first check failure.
• Split CI installation into role-specific pak dependency plans and preserved resolved-library caches when later workflow stages fail.
• Bounded dependency installation in every workflow so a stalled package resolver fails promptly instead of consuming an entire job timeout.
• Consolidated routine Linux build, check, coverage, and pkgdown work behind one uncached dependency installation while retaining parallel macOS and Windows checks. This avoids intermittent cache-service stalls across duplicated Linux setup jobs.
• Added version-tag release-candidate builds and tag/published-release BiocCheck workflows. Release artifacts are built in temporary storage and are not published automatically.

pepVet 0.1.7

Empirical concordance

• Added a reproducible PeptideAtlas concordance analysis. In the sampled human tryptic digests, peptides inside the default length and GRAVY windows had a 38.0 percentage-point higher mean observation rate than peptides outside them. The result is limited to the sampled data and is not an experimental calibration of pepVet scores.
• Added bounded grid-search and threshold-calibration analyses, documented their limits, and retained the current defaults as strict, conservative settings by design.
• Corrected the concordance artifacts to store full protein lengths and regenerated the committed CSV and RDS files.

Package quality

• Standardized docstrings, limitations, error handling, plot conventions, package-qualified calls, comments, and line formatting across the source.
• Unified GRAVY calculation under one vectorized helper and removed stale helper references from package and data-generation code.
• Removed inactive GitHub workflow files and generated vignette data from version control so the repository matches the current release process.

Fixes

• Fixed edge cases in row binding, cleavage-efficiency summaries, GRAVY missing-value handling, and sensitivity plot validation.
• Fixed recommend_enzyme() tie handling so all enzymes within tolerance are returned in alphabetical order.
• Corrected charge scoring for single-residue peptides so terminal basic residues are not counted as internal charge sites.
• Fixed plot configuration updates so invalid changes leave the active configuration unchanged.

pepVet 0.1.6

New functions

• score_diagnostics() runs VIF, PCA, and ablation analyses on a batch_evaluate() result to quantify multicollinearity, dimensionality, and component importance in the scoring model.
• plot_score_diagnostics() visualises the diagnostics result as a three-panel figure: VIF bar chart with severity-colored bars, PCA scree plot with cumulative variance, and ablation waterfall with error bars and verdict-flip counts.

New documentation

• Added Score Diagnostics for pepVet Scoring Models article covering VIF, PCA, and ablation analysis with worked examples.
• Added pepVet in the Tool Landscape article comparing pepVet against MS-Digest, ExPASy PeptideMass, Protein Cleaver, ProteaseGuru, and PeptideRanger.
• Added diagnostics cross-reference to the introduction vignette.

Bug fixes

• Fixed sensitivity_analysis() batch-mode verdict instability: now uses full 3-level classification (Good/Moderate/Poor) instead of checking only the Good boundary.
• Fixed vignette pipe example where recommend_enzyme() received a comparison tibble instead of a protein sequence.
• Fixed tool-comparison vignette: replaced fragile ../inst/extdata/ paths with system.file().
• Fixed verdict threshold table in introduction vignette: said 0.7 / 0.4, code uses 0.65 / 0.40.

Housekeeping

• Refactored zzz.R to avoid the lockBinding R CMD check NOTE while preserving active bindings for mutable plot configuration.
• Fixed README installation instructions (removed S4Vectors from BiocManager install; pulled in automatically by Biostrings).
• Enabled automatic CI triggers for R CMD check on push and PR across ubuntu, macOS, and Windows.
• Added .gitattributes, .Rbuildignore updates, .onAttach removal, and cli cleanup.
• Docstring standardisation and .bind_rows() type-safety improvements.

pepVet 0.1.5

New functions

• sensitivity_analysis() performs Monte Carlo weight perturbation via Dirichlet sampling. Reports simulated verdict frequencies, composite intervals, rank stability (top-1, Kendall tau), per-protein instability in batch mode, weight importance (R squared), and corner-case composites. Optional importance and corner_cases diagnostics.
• plot_weight_sensitivity() generates a verdict-coloured density ridge plot from a sensitivity analysis result, with threshold lines and a rug mark at the default composite score.

Scoring

• Zero-cleavage hard-fail: proteins with no cleavage sites for a given enzyme now receive composite = 0 and verdict = "Poor" regardless of other scores. Previously an uncuttable protein with ideal length/hydro/charge could score up to 0.426, crossing the Moderate threshold. The fix belongs in the scoring engine so sensitivity analysis treats these as deterministic negative controls.

Plot fixes

• plot_digest_profile() coverage panel now filters to the exact requested MC level instead of showing all levels. Overlapping peptides are stacked into sub-tracks via greedy interval packing, and the panel title includes the MC level. Gap overlays remain but the subtitle no longer counts uncovered regions; a small italic caption notes when some gaps are too narrow to render at plot scale.

Site

• Updated pkgdown color palette to match the new pepVet logo colors. Primary/secondary swapped for better link contrast. Favicons regenerated.
• Replaced all logo references with the new pepVet-logo.png. Navbar shadow, rounded code blocks, sticky TOC sidebar added.
• Flattened the Articles dropdown. Removed redundant "Getting Started" entry and section headers.
• Added prev/next navigation buttons to reference pages (client-side JS).

pepVet 0.1.4

Housekeeping

• Standardised cli error messages across the package. Replaced all paste0("{.arg ", var, "}") patterns with "{.arg {var}}" cli glue syntax in .abort(), cli_warn(), and cli_inform() calls. Also converted "i" bullet paste() calls to {.val {x}} formatters.
• Added .bind_rows() helper and replaced all bare do.call(rbind, ...) calls with it. The helper returns an empty tibble for empty input instead of failing silently.
• Replaced import(cleaver) with @importFrom cleaver cleavageRanges. Removed the .cleavage_ranges workaround via get("cleavageRanges", envir = asNamespace("cleaver")) and now calls cleaver::cleavageRanges() directly.
• Removed dead code: .compute_difficulty_flags() in evaluation.R was defined but never called. Its logic was superseded by .batch_difficulty_flags().
• Made plot_coverage_map() gradient stops (color_by = "hydrophobicity") data-driven instead of hardcoding the GRAVY valid-range boundary at 0.6. The 4 color stops are now evenly spaced across the actual GRAVY range of the displayed peptides.
• Suppressed three R CMD check notes by adding .lintr, tmp/, and paper/ to .Rbuildignore.
• Added missing @return roxygen tags to 10 internal helper functions across the source.
• Removed duplicate .classify_verdict() from plot_utils.R. The function was defined in both scoring.R and plot_utils.R with identical logic; the duplicate silently shadowed the original due to file-sourcing order.
• Standardised patchwork title and tag sizes across all plot functions. Added patchwork_tag_size to .pepvet_params. Fixed plot_gravy_landscape() title size 13 -> 15. Changed plot_enzyme_comparison(), plot_digest_profile(), plot_proteome_overview(), plot_batch_comparison() to use .get_param() for tag sizes instead of hardcoded 14.
• Fixed plot_batch_comparison() heatmap colorbar to use explicit unit(..., "pt") instead of numeric (lines) values.

Bug fixes

• Fixed .onLoad() failure when called on an already-loaded namespace. The rm() call on locked namespace bindings was guarded with bindingIsActive() checks so the active-binding installation runs exactly once.

pepVet 0.1.3

Defaults

• Changed default missed_cleavages from 0L to 1L across all evaluation functions. MC=1 reflects standard bottom-up proteomics practice; MC=0 produces unrealistically poor scores for every enzyme.
• Changed default scoring weights to documented expert-prior values: S_length = 0.200, S_coverage = 0.348, S_count = 0.226, S_hydro = 0.138, S_charge = 0.088. The derivation record needed to support the earlier method and consistency-ratio description was not retained, so those claims have been removed.
• Lowered the Good verdict threshold from 0.70 to 0.65 to better align with the observed score distribution under the new weights. Centralised verdict thresholds in .pepvet_params accessed via .get_param().

Performance

• digest_protein() rewritten for batch workloads. .cleavage_ranges() is now called once on the full AAStringSet instead of once per protein, eliminating repeated S4 dispatch overhead. The non-efficiency path pre-allocates six output vectors and fills them in a single loop before constructing one tibble, replacing ~20 K individual tibble builds followed by do.call(rbind, ...).
• batch_evaluate() restructured around two bulk calls, one digest_protein() and one score_peptides() for the entire input, instead of a per-protein loop over evaluate_digest(). A new internal helper .batch_difficulty_flags() computes all four difficulty flags across all proteins simultaneously via tabulate(), tapply(), and a vectorized GRAVY calculation, replacing ~20 K per-protein subset/GRAVY/tibble::as_tibble() cycles.
• triage_proteins() fully vectorized. Row-by-row vapply logic replaced with nested ifelse() and a rowSums(matrix < 0.5) component check, making the function O(n) in a single pass.
• S_coverage scoring no longer uses IRanges::reduce(). Overlapping intervals are now merged inline via order() + cummax() on sorted starts and ends. Same result with no S4 dispatch.
• Scoring helpers (S_coverage, S_count, S_hydro, S_charge) accept a pre-computed valid_digest argument so callers can extract valid peptides once and share it across all four components instead of calling .extract_valid_digest() four times per protein.

New functions

• Added batch_compare_enzymes() to score an entire proteome against multiple enzymes in one call, returning a tidy tibble of class pepvet_batch_comparison with one row per protein-enzyme pair. Parallel execution is supported via parallel::mclapply on Unix (fork copy-on-write, zero serialization overhead) and parallel::parLapply on Windows; both are part of base R. Proteins are split into equal chunks, so all cores workers are utilised regardless of the number of enzymes.

Parallel robustness

• Fixed a bug in batch_evaluate() where parallel::mclapply worker crashes produced silently corrupted results. Failed chunks are now detected and retried sequentially.

Amino acid data

• Added U (selenocysteine, Sec) to the aa_properties reference table. 25 human proteins contain selenocysteine and were previously rejected during input validation.
• Added O (pyrrolysine, Pyl) to the aa_properties reference table (row 22). Monoisotopic mass verified from PubChem CID 119813 and ChEBI CHEBI:91273 (C₁₂H₂₁N₃O₃, 255.15829 Da). Hydrophobicity and pKa are NA: the Kyte-Doolittle scale predates the discovery of pyrrolysine (1982 vs 2002), and the ε-amino group is tied up in an amide bond and is not titratable. calculate_gravy() now passes na.rm = TRUE so sequences containing O return a valid GRAVY score computed from the remaining residues.

Removals

• Removed plot_enzyme_protein_heatmap(). The 2D tile matrix did not add enough over the other comparison functions (plot_enzyme_comparison(), plot_batch_comparison()) to justify maintenance.
• Removed plot_component_scatter(). The 2D scatter of component scores was redundant with the information already visible in plot_proteome_overview() and plot_batch_comparison().
• Removed plot_batch_summary(). The two-panel overview was superseded by the richer plot_proteome_overview() and plot_batch_comparison().
• Removed plot_protein_comparison(). The grouped bar chart did not add enough insight beyond plot_enzyme_comparison() and the batch-level comparison functions.

pepVet 0.1.2

Visualization

• Added plot_digest_profile() as a four-panel single-protein diagnostic showing length distribution, GRAVY scatter, coverage map, and component scores.
• Added plot_coverage_map() for horizontal sequence coverage visualisation with valid/invalid peptide segments and missed-cleavage expansion lanes.
• Added plot_cleavage_map() for vertical cleavage-site ticks with fragment blocks and optional efficiency coloring from annotate_cleavage_sites().
• Added plot_enzyme_comparison() for comparing component scores across multiple enzymes with sorted bars and a top-score badge.
• Added plot_protein_comparison() for comparing component scores across multiple proteins under a single enzyme with verdict badges.
• Added plot_enzyme_protein_heatmap() for a 2D tile matrix of proteins versus enzymes with composite-score gradient and verdict overlay.
• Added plot_length_distribution() for peptide-length histograms with valid-range shading and multi-input faceted mode.
• Added plot_gravy_landscape() for 2D scatter of length versus GRAVY with valid-region rectangle and multi-input comparison.
• Added plot_pI_distribution() for isoelectric-point histograms with fraction-bin coloring and multi-input density overlay.
• Added plot_missed_cleavage_impact() for showing how component scores change across MC=0/1/2.
• Added plot_batch_summary() for two-panel proteome overview: verdict histogram and score-versus-length scatter.
• Added plot_proteome_heatmap() for hierarchical clustering of component scores across a batch. Requires pheatmap (guarded).
• Added plot_component_scatter() for 2D scatter of any two score components across all batch proteins.
• Added shared infrastructure in R/plot_utils.R: .pepvet_pal colour palette, .pepvet_theme() base theme, and reusable panel builders.

Housekeeping

• Established coding conventions and standardisation strategy for consistency across the package.

pepVet 0.1.1

Batch evaluation, triage, and export

• batch_evaluate() now returns a flat tibble with one row per protein instead of a named list of evaluate_digest() results. Columns: protein_id, protein_length, n_peptides, n_valid_peptides, all component scores, composite_score, verdict, median_peptide_length, and four sequence-level difficulty flags. This is a breaking change for any code that accessed results via batch[[protein_id]]$scores.
• Added summarize_batch() to extract aggregate statistics from the batch tibble: verdict distribution, composite score distribution, per-component means, bottom-10% problem proteins, and heuristic enzyme-switch candidates.
• Added triage_proteins() to append an action column ("proceed", "consider_alternative", "try_other_enzyme", "skip") to the batch tibble based on verdict and sequence-level difficulty flags.
• Added pepvet_check() as a single-call convenience wrapper: evaluates a protein digest and immediately prints a styled console report. Returns the evaluate_digest() result invisibly.
• Added export_peptide_list() in a new R/export.R module. Exports valid peptides in "skyline" (precursor-charge CSV with computed m/z for Skyline import), "generic" (annotated CSV with GRAVY, pI, and validity), or "fasta" format. Writes to a file when file is specified; returns a tibble or character vector otherwise.
• Fixed export_peptide_list() generic format to include a pI column alongside gravy and valid.

pepVet 0.1.0

Digestion and annotations

• Added annotate_cleavage_sites() for sequence-local cleavage-efficiency annotation of trypsin-family digestion sites.
• Added optional cleavage_efficiency output in digest_protein() so peptide tables can carry high/medium/low cleavage-risk context without changing the default schema.
• Added n_high_efficiency_sites and n_low_efficiency_sites to evaluate_digest() output as informational protein-level summaries.

Scoring and utilities

• Added peptide mass and pI utilities plus residue-level monoisotopic mass data for fractionation-aware planning workflows.
• Retained preset tracking through preset_used so score tables can distinguish shipped workflows from custom configurations.

Documentation

• Reworked the README and core articles for the 0.1.0 release so digestion, scoring, presets, and cleavage annotations are explained as one coherent planning workflow.

pepVet 0.0.4

Scoring

• Reworked S_count to use an enzyme-aware expected peptide length instead of a fixed trypsin-derived constant.
• Added median_peptide_length to scoring output so enzyme comparisons show the denominator behind S_count.
• Added configurable gravy_range and length_range arguments across the scoring and evaluation helpers.
• Added pepvet_preset() with presets for standard DDA, DIA, targeted assays, membrane proteomics, FFPE-style degraded samples, and fractionated workflows.
• Clarified that S_charge tracks extra internal basic-residue richness, not baseline peptide ionizability.
• Added preset_used metadata to scoring output and evaluate_digest() params so named presets and custom scoring configurations can be distinguished explicitly.

Documentation

• Rewrote the package website copy, docstrings, README, and articles for v0.0.4 with detailed workflow guidance and preset-specific examples.
• Added a dedicated article on workflow presets, including practical examples and use-case notes for each preset.
• Added scoring-model positioning, evidence-basis, scope, and known-limitations guidance so heuristic and literature-backed assumptions are documented in-package.

Site

• Updated pkgdown navigation to surface the preset guide alongside the core workflow articles.

pepVet 0.0.3

New functions

• evaluate_digest() wraps digest_protein() and score_peptides() into a single call.
• compare_digests() runs multi-enzyme comparison for a single protein, sorted by composite score.
• recommend_enzyme() returns the top-scoring enzyme name from a comparison.
• batch_evaluate() runs evaluate_digest() across every protein in a multi-FASTA file.
• digest_report() prints styled console output for evaluation and comparison results, with colour-coded bar charts and ranked tables.

Documentation

• Rewrote README.md with scoring component table, reference fixture table, and workflow diagram.
• Expanded the getting-started vignette to cover all seven exported functions end-to-end.
• Added Choosing a Proteolytic Enzyme article covering enzyme biology, worked comparisons on BSA, Histone H3.1, and alpha-synuclein isoforms, and guidance for membrane proteins, phosphoproteomics, and IDPs.
• Added Understanding the Scoring Model article with mathematical definitions for all components, weight customisation guidance, verdict calibration notes, and known limitations.

Site

• Configured pkgdown site with structured navbar, grouped reference index, and flatly Bootstrap 5 theme.

pepVet 0.0.2

Core engine

• digest_protein() performs cleaver-compatible digestion with validated input handling for character sequences, AAString, AAStringSet, and FASTA paths.
• score_peptides() computes five component scores (S_length, S_coverage, S_count, S_hydro, S_charge) and optional proteome-aware S_unique.

Data

• Added aa_properties reference tibble with Kyte-Doolittle hydrophobicity, molecular weight, and side-chain pKa values.
• Added eight reference FASTA fixtures in inst/extdata/.

CI

• Established GitHub Actions workflows for R CMD check and lint.