Variant Surveillance

What the source does

• FilesystemNone observedNo reads or writes in the source
• NetworkNone observedNo outbound calls in the source
• ShellNone observedNo commands run in the source
• DependenciesPinnedNothing floats
• SecretsNone foundNo keys in source

Five audit layers

Gates applied: no behavioural pass.

Audit 0.4.1 · source sha c8c1fc3a2b13 · 19 Oct 2026Report an issue or request a re-scan

• PublisherGPTomics GitHub organizationOwner of the repository this skill is read from
• Source folderGPTomics/bioSkills/epidemiological-genomics/variant-surveillanceThe exact folder we audited
• LicenceMITAs the repository states it
• Commit pinned for this verdictc8c1fc3a2b13A new audit runs when the source changes
• Repository statusArchivedLast push 65 days ago
• Sandboxed runNot runSkills are read, not executed; layer L4 is skipped

Its description: Assigns pathogen lineages (SARS-CoV-2 Pangolin UShER mode; Nextclade clade + QC; pango-designation alias resolution) and tracks variant frequencies over time using Nextstrain (Augur + Auspice), wastewater deconvolution…

---
name: bio-epidemiological-genomics-variant-surveillance
description: Assigns pathogen lineages (SARS-CoV-2 Pangolin UShER mode; Nextclade clade + QC; pango-designation alias resolution) and tracks variant frequencies over time using Nextstrain (Augur + Auspice), wastewater deconvolution (Freyja, COJAC, alcov, lineagespot), lineage-fitness modelling (multinomial logistic), and recombinant detection (3SEQ, RDP4, Bolotie). Covers Pangolin pangolin-data and Nextclade dataset version pinning (mandatory; lineage-defining mutations change with dataset), Freyja barcode forward-only date constraint, ARTIC primer scheme churn (V3/V4/V4.1/V5.3.2/Midnight) with dropout regions, and recombinant X-prefix designation lag. Use when assigning Pango lineages and Nextclade clades to viral consensus sequences, building Nextstrain Augur surveillance pipelines, deconvolving wastewater into lineage frequencies with Freyja, tracking lineage frequencies over time, handling ARTIC primer dropouts, or running surveillance for SARS-CoV-2/influenza/Mpox/RSV/H5N1/measles.
tool_type: mixed
primary_tool: Pangolin
---

## Version Compatibility

Reference examples tested with: pangolin 4.3+ (pangolin-data 1.30+), nextclade 3.8+, augur 24.0+, freyja 1.4+, cojac 0.9+, lineagespot 1.6+ (Bioconductor), usher 0.6+, matUtils 0.6+, samtools 1.20+, lofreq 2.1+, ivar 1.4+, ARTIC pipeline 1.3+, snakemake 8.5+, pandas 2.2+, BioPython 1.84+, jq 1.7+.

Before using code patterns, verify installed versions match. If versions differ:
- `pangolin --all-versions` -- prints pangolin + pangolin-data + scorpio + constellations versions
- `nextclade dataset list --tag latest sars-cov-2` -- list current dataset tags
- `freyja --version`; `freyja barcode-build --help` (note: HYPHEN, not underscore; some legacy docs show `barcode_build`)
- `nextclade run --help` -- v3+ syntax replaced v2; old `nextclade` invocation no longer works
- `augur --version`; `augur refine --help` for current root-strategy flags

If `pangolin --inference usher` is rejected, the flag is `--analysis-mode usher` (no `--inference`). If `nextclade --input-dataset DIR` works, the installed version may be v2; v3 accepts both but `--dataset NAME` is the modern form for built-in datasets. Pangolin and Nextclade output column names differ between major releases -- introspect rather than retry.

# Variant Surveillance

**"Which lineages are circulating, and how fast are they growing?"** -> Assign consensus or wastewater samples to a curated lineage / clade nomenclature, then track frequencies over time with explicit version pinning. The lineage assignment is NOT a stable property of the sequence; it is a property of the sequence interpreted by a specific pangolin-data / Nextclade-dataset version. Two labs running the same Pangolin binary with different pangolin-data versions can produce different calls on the same genome. For published or regulatory output, pin BOTH the executable AND the dataset version (`pangolin --all-versions`; `nextclade dataset list --tag latest`), and re-run the whole archive after every dataset update -- comparing today's BA.2.86 call to last month's "Unassigned" call is invalid.

- CLI: `pangolin sequences.fasta --analysis-mode usher --outfile lineage_report.csv` -- UShER mode is the default since v4 (pangoLEARN deprecated mid-2023)
- CLI: `nextclade run --input-dataset nc_dataset/sars-cov-2 --output-tsv nc.tsv sequences.fasta` -- clade + Pango + QC + mutations
- CLI: `freyja variants sample.bam --variants sample.variants.tsv --depths sample.depths.tsv --ref reference.fa` then `freyja demix sample.variants.tsv sample.depths.tsv --output sample.demix.tsv` -- wastewater lineage deconvolution
- CLI: `augur refine --tree tree.nwk --alignment aln.fasta --metadata meta.tsv --output-tree refined.nwk --root oldest --timetree` -- Nextstrain time-scaling

## The Single Most Important Modern Insight -- Lineage assignment is dataset-version-dependent

A SARS-CoV-2 sequence called BA.5 today might be called BA.5.2.1 next week and KP.3 a month after that. pangolin-data and nextclade-dataset are updated weekly; lineage definitions evolve through pango-designation GitHub issues, often days-to-weeks before pangolin-data releases include the lineage. During the lag window, the same genome submitted in lab A (older pangolin-data) and lab B (current) gets different calls. The cross-lab "different lineage" result is then misread as biology. For any report, pin BOTH the executable AND the dataset version with `pangolin --all-versions` and `nextclade dataset list --tag latest` recorded alongside the call. For longitudinal studies, re-run the WHOLE archive after every dataset update -- comparing today's BA.2.86 call against last month's "Unassigned" call is invalid. Second-order insight: Pangolin's pangoLEARN mode was officially deprecated mid-2023 in favour of UShER mode (Pongmoragot 2024 *Virus Evol* 10:vead085); cross-study comparison of XBB sub-lineage prevalence from 2022 - mid-2023 is contaminated by the pangoLEARN -> UShER mode switch even when the same pangolin-data version is used.

## Algorithmic Taxonomy

| Tool | Mechanism | Inputs | Output | Strength | Fails when |
|------|-----------|--------|--------|----------|------------|
| Pangolin UShER mode (O'Toole 2021 *Virus Evol* 7:veab064; Pongmoragot 2024 *Virus Evol* 10:vead085) | Parsimony placement on daily-updated UShER mutation-annotated tree | SARS-CoV-2 consensus | Pango lineage call | UShER is the default since v4; more accurate than pangoLEARN for recent / divergent lineages | Designation lag for emerging lineages; recombinants require manual Pango-X designation |
| Pangolin pangoLEARN mode | Random-forest classifier trained on pangolin-data | SARS-CoV-2 consensus | Pango lineage call | Fast | DEPRECATED mid-2023; less accurate than UShER for novel sub-lineages |
| Nextclade (Aksamentov 2021 *JOSS* 6:3773) | Reference-tree placement + clade assignment + mutation calling + QC | Viral consensus (multi-pathog

Excerpt, first 6,000 characters of SKILL.md, verbatim from the audited commit. It is text from someone else’s repository, quoted so you can judge it before your agent reads it.

pip install pandas biopython

git clone https://github.com/GPTomics/bioSkills
git -C bioSkills checkout c8c1fc3a2b13

Works in

1. 2026-10-19
   ✓SAFE B 89 / 100

   first audit · source c8c1fc3a2b13

Questions about Variant Surveillance

• github.com/GPTomics/bioSkills/tree/main/epidemiological-genomics — the audited source at commit c8c1fc3a2b13 and every finding aboveObserved · 19 Oct 2026

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