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tooluniverse-protein-sae-variant-interpretation

Interpret a missense variant via ESMC-6B Sparse Autoencoder (SAE) feature activations. For a given protein + variant, computes which interpretable SAE features (catalytic, ligand-binding, PTM, structural motif, domain, etc.) are lost or gained at the mutation site. Use when standard pathogenicity scores (AlphaMissense, ClinVar) say a variant is damaging but you need a MECHANISTIC explanation — e.g. 'why is this variant LoF?' Complements (does not replace) variant-interpretation and variant-to-mechanism skills, which focus on ACMG classification or regulatory mechanism.

74

Quality

93%

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SecuritybySnyk

Low

Low-risk findings worth noting

The canonical home for this skill is tooluniverse-protein-sae-variant-interpretation in mims-harvard/ToolUniverse

SKILL.md
Quality
Evals
Security

Quality

Content

88%Weight 40%Scale 1-5

Reviews the quality of instructions and guidance provided to agents. Good implementation is clear, handles edge cases, and produces reliable results.

A strong, dense operational skill: executable tool calls with expected outputs, explicit ref-residue validation before mutation, honest limitations, and a cross-validation checklist. Its only real gaps are minor — a few could-be-trimmer explanations of things Claude already knows, and secondary material (long path, interpretation table) inlined in a single 245-line file that could be split into one-level-deep references.

Suggestions

Trim redundant indexing reminders ('Python is 0-indexed, position is 1-indexed' appears twice) and the background definition of SAE features in the intro — Claude needs the workflow, not the primer.

Move the long path (Steps 4-5), the interpretation category table, and the cross-validation layer table into a references/ file (e.g. references/sae-interpretation.md) linked from the main workflow, keeping SKILL.md as a lean overview plus the quick path.

DimensionReasoningScore

Conciseness

Mostly lean and operational — tool calls with expected outputs, cost/latency notes, and a compact reporting template — with only minor trimmable fat: 'Verify ref_sequence[174] == "R" (Python is 0-indexed, position is 1-indexed)' and 'Python is 0-indexed' restate what Claude already knows, and the opening line 'SAE features are interpretable latent dimensions of the model's hidden state' is light background. Not enough padding to drop to anchor 3's 'noticeably could be tightened'; well above anchor 2.

4 / 5

Actionability

Fully executable end-to-end: concrete tool invocations with parameters and documented return shapes (ESM_explain_variant_mechanism, ESM_score_variant_sae_disruption, ESM_score_variant_sae_batch, ESM_get_sae_features), complete runnable delta-aggregation code, a saturation-variant recipe, and a copy-ready reporting template. Edge behavior is documented ('both tools return a clear error'), covering the common cases like the anchor-5 example.

5 / 5

Workflow Clarity

A clearly sequenced 5-step workflow with an explicit validation checkpoint — 'Verify ref_sequence[174] == "R"' and 'If the reference residue does NOT match, return an explicit error — do not silently mutate the wrong position' — plus error-recovery guidance ('you supplied the wrong isoform / mis-labeled the variant') and a cross-validation checklist for high-stakes calls. The batch/saturation path inherits the same validation, so the batch-validation cap does not apply.

5 / 5

Progressive Disclosure

No bundle files exist (references/, scripts/, assets/ are absent), so everything is inline in a single well-sectioned SKILL.md (~245 lines) with clear headers — 'When to use this skill', 'Required inputs', 'Prerequisites', 'Workflow (5 steps)', 'Interpretation table', 'Honest limitations', 'Cross-validation pattern', 'Reporting format'. Navigation is easy and there is zero reference nesting, but the long-path steps, interpretation table, and cross-validation layers are secondary material that could live in one-level-deep reference files, which keeps it at anchor 4 rather than 5 (which expects content appropriately split across files).

4 / 5

Total

18

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20

Passed

Description

95%Weight 40%Scale 1-5

Based on the skill's description, can an agent find and select it at the right time? Clear, specific descriptions lead to better discovery.

An exemplary description: concrete capability statements, an explicit 'Use when' clause with user-voiced trigger phrases, and explicit boundary demarcation against sibling skills. The only mild weakness is that it names roughly two concrete actions rather than a longer list, which keeps specificity at 4 rather than 5.

DimensionReasoningScore

Specificity

Concrete actions are explicit — 'Interpret a missense variant via ESMC-6B Sparse Autoencoder (SAE) feature activations' and 'computes which interpretable SAE features (catalytic, ligand-binding, PTM, structural motif, domain, etc.) are lost or gained at the mutation site' — with the feature categories adding specificity. It stops just short of the 5 anchor's 'multiple specific concrete actions; comprehensive coverage' (essentially two actions), but well above anchor 3's '1-2 concrete actions, not comprehensive' because the enumerated categories and the lost/gained framing make coverage broad.

4 / 5

Completeness

Explicitly answers both: what — 'computes which interpretable SAE features ... are lost or gained at the mutation site'; when — 'Use when standard pathogenicity scores (AlphaMissense, ClinVar) say a variant is damaging but you need a MECHANISTIC explanation'. Both are concrete and use explicit trigger phrasing, matching the anchor-5 example structure.

5 / 5

Trigger Term Quality

Comprehensive natural terms with synonyms: 'missense variant', 'damaging', 'pathogenicity scores', 'AlphaMissense', 'ClinVar', 'LoF', 'mechanistic explanation', and the user-voiced phrase "why is this variant LoF?". These are exactly the phrases a user would say when needing this skill; no significant synonym gaps (score 4's 'a few natural terms missing' doesn't apply).

5 / 5

Distinctiveness Conflict Risk

Clear niche (SAE-based mechanistic explanation of missense variants) plus explicit de-confliction: 'Complements (does not replace) variant-interpretation and variant-to-mechanism skills, which focus on ACMG classification or regulatory mechanism'. This actively routes adjacent requests to sibling skills, minimizing wrong-skill triggering.

5 / 5

Total

19

/

20

Passed

Validation

100%

Checks the skill against the spec for correct structure and formatting. All validation checks must pass before discovery and implementation can be scored.

Validation — 16 / 16 Passed

Validation for skill structure

No warnings or errors.

Repository
mims-harvard/ToolUniverse
Reviewed

Table of Contents

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