seqeron-protein-features

name	seqeron-protein-features
description	Predict features of a PROTEIN sequence with Seqeron (MCP tools OR the C# API). Use for intrinsic disorder / IDRs (TOP-IDP) and MoRFs, signal-peptide prediction + cleavage site, transmembrane helices & membrane topology, coiled-coil regions, protein domains, PROSITE / common protein motifs, protein low-complexity (SEG) regions, and Kyte–Doolittle hydrophobicity profiles. Triggers: "predict disorder in this protein", "find the intrinsically disordered regions", "find the signal peptide / where is it cleaved", "transmembrane regions of this protein / membrane topology", "coiled-coil prediction", "what domains / PROSITE motifs are in this protein", "hydrophobicity plot", "is this residue disorder-promoting". Input is an AMINO-ACID sequence. Server: analysis.
allowed-tools	Read, Bash, Grep, Glob

seqeron-protein-features — disorder/IDRs, signal peptide, TM, coiled-coil, domains/motifs, hydrophobicity

Routing + orchestration skill for the protein-feature-prediction family on the Analysis server (backing classes DisorderPredictor.*, ProteinMotifFinder.*, plus SequenceStatistics for the hydrophobicity profile). Input is always a protein (amino-acid) sequence. It picks the right tool and gives a dual-mode recipe (MCP tool call and the equivalent Seqeron.Genomics C# Method ID).

• Rigor is delegated. Tool-only computation, envelope, provenance, cross-check, coordinate reporting, and the alpha / not-for-clinical caveat are owned by bio-rigor — it applies by default; do not restate its rules.
• Don't know a tool name? Use seqeron-discovery (python3 scripts/skills/find-tool.py <kw> --server analysis) — never guess.
• Point, don't duplicate. Full I/O schemas live in docs/mcp/tools/analysis/<tool>.md; algorithm invariants in docs/algorithms/ProteinPred/ + docs/algorithms/ProteinMotif/. This skill links, it does not copy.

Scope boundary — protein features vs DNA annotation

This skill OWNS the protein-SEQUENCE feature family. The overloaded bio-annotation name-drops it but its real subject is DNA-shaped annotation. Route by input:

• PROTEIN input → here. Disorder, MoRFs, signal peptide, TM helices, coiled-coils, protein domains, protein PROSITE / common motifs, protein SEG low-complexity, hydrophobicity.
• DNA/RNA input → bio-annotation. ORFs/genes/promoters, variants, DNA motifs (exact/degenerate/PWM, MotifFinder.*), nucleotide low-complexity/DUST (SequenceComplexity.*), repeats, k-mers, splicing, methylation, RNA structure. Do not confuse ProteinMotifFinder.FindMotifByProsite (protein, here) with the DNA motif tools there. If you only have DNA, translate to protein first via bio-qc (translate) before entering this skill.

Decision guide — which tool for which question

Question (protein input)	Tool ([MCP] / Method ID)
Per-residue disorder + IDRs + disorder content (TOP-IDP)	predict_disorder / DisorderPredictor.PredictDisorder ⚠ confidence guarded
Molecular-recognition features within disorder	predict_morfs / DisorderPredictor.PredictMoRFs
Single amino-acid disorder propensity / is-promoting	disorder_propensity · is_disorder_promoting / DisorderPredictor.GetDisorderPropensity · .IsDisorderPromoting
Protein low-complexity (SEG) — from the disorder engine	predict_low_complexity_seg / DisorderPredictor.PredictLowComplexityRegions
Protein low-complexity (SEG) — from the motif engine	find_protein_low_complexity_regions / ProteinMotifFinder.FindLowComplexityRegions
N-terminal signal peptide + cleavage site	predict_signal_peptide / ProteinMotifFinder.PredictSignalPeptide
Transmembrane helices + membrane topology	predict_transmembrane_helices / ProteinMotifFinder.PredictTransmembraneHelices
Coiled-coil regions (heptad / MTIDK-style)	predict_coiled_coils / ProteinMotifFinder.PredictCoiledCoils
Protein domains	find_protein_domains / ProteinMotifFinder.FindDomains
Common protein sequence motifs	find_protein_motifs / ProteinMotifFinder.FindCommonMotifs
Scan a PROSITE pattern in a protein	find_motif_by_prosite / ProteinMotifFinder.FindMotifByProsite
Compile a PROSITE pattern → regex	prosite_to_regex / ProteinMotifFinder.ConvertPrositeToRegex
Kyte–Doolittle hydrophobicity profile	hydrophobicity_profile / SequenceStatistics.CalculateHydrophobicityProfile

⚠ Envelope note. predict_disorder's per-residue / per-region confidence is DISORDER-REGION-001 (uncalibrated). See the STOP rule below. The region boundaries themselves follow the validated TOP-IDP threshold and are fine to report.

Canonical dual-mode pipelines

Coordinates: protein positions are 0-based residue indices; regions are [start,end] inclusive per the tool doc. Report the base explicitly.

(a) Disorder + IDRs → MoRFs (intrinsic-disorder characterization)

1. [MCP] predict_disorder(sequence, windowSize?=21, disorderThreshold?=0.542, minRegionLength?=5) → residuePredictions, disorderedRegions[{start,end,meanScore,confidence,regionType}], overallDisorderContent.
2. [MCP] predict_morfs(sequence, minLength?=10, maxLength?=25) → MoRF intervals within disordered context.

• [C# API] DisorderPredictor.PredictDisorder(...) → .PredictMoRFs(...).
• Envelope: report region boundaries + overallDisorderContent; treat confidence as uncalibrated (DISORDER-REGION-001). If a validated per-region call is required, use the DisorderPredictor.PredictDisorderRegions branch and STOP rather than raising the mode (below).
• Cross-check: an IDR should overlap a hydrophobicity minimum from pipeline (e) and (usually) a protein SEG low-complexity region.

(b) Membrane / secretion topology → signal peptide + TM helices

1. [MCP] predict_signal_peptide(proteinSequence, prokaryote?=false) → signal-peptide presence + cleavage site.
2. [MCP] predict_transmembrane_helices(proteinSequence, windowSize?=19, threshold?=1.6) → TM segments + in/out topology.

• [C# API] ProteinMotifFinder.PredictSignalPeptide(...) → .PredictTransmembraneHelices(...).
• Cross-check: each TM segment should sit on a hydrophobicity peak from pipeline (e); a called signal peptide occupies the N-terminus and should not be double-counted as TM1.

(c) Structural / functional motifs → coiled-coils + domains + PROSITE

1. [MCP] predict_coiled_coils(proteinSequence, windowSize?=28, threshold?=0.5) → coiled-coil intervals + score.
2. [MCP] find_protein_domains(proteinSequence) → domain calls; find_protein_motifs(proteinSequence) → common motifs.
3. [MCP] targeted PROSITE: find_motif_by_prosite(proteinSequence, prositePattern, motifName?) → hits; prosite_to_regex(prositePattern) inspects the compiled regex first.

• [C# API] ProteinMotifFinder.PredictCoiledCoils(...) · .FindDomains(...) · .FindCommonMotifs(...) · .FindMotifByProsite(...) · .ConvertPrositeToRegex(...).
• Cross-check: confirm a PROSITE hit's residue span against prosite_to_regex before interpreting.

(d) Protein low-complexity (SEG) masking before motif interpretation

1. [MCP] predict_low_complexity_seg(sequence, triggerWindow?=12, triggerThreshold?=2.2, extensionThreshold?=2.5, minLength?=1) or find_protein_low_complexity_regions(proteinSequence, windowSize?=12, triggerComplexity?=2.2, extensionComplexity?=2.5) → SEG intervals.

• [C# API] DisorderPredictor.PredictLowComplexityRegions(...) or ProteinMotifFinder.FindLowComplexityRegions(...).
• Both are protein SEG. Use as a filter: down-weight domain/PROSITE hits that fall inside SEG regions (compositionally biased, prone to spurious matches).

(e) Hydrophobicity profile (supporting evidence)

1. [MCP] hydrophobicity_profile(proteinSequence, windowSize?=9) → per-window Kyte–Doolittle score.

• [C# API] SequenceStatistics.CalculateHydrophobicityProfile(...).
• Feeds cross-checks: peaks corroborate TM helices (b); troughs corroborate IDRs (a).

Envelope — STOP rule (guarded unit in scope)

• DISORDER-REGION-001 (predict_disorder / DisorderPredictor.PredictDisorder, output the per-residue / per-region confidence) is Permissive-only (blocked in Strict & Moderate; default is Moderate). No disorder predictor publishes a calibrated confidence standard. If a task requires a validated per-region confidence and the call would run below its MinimumMode (throws SeqeronLimitationException), STOP and report the envelope — do not raise the mode to force output (bio-rigor rule). Named alternative: the region boundaries are validated (TOP-IDP threshold), so report those + overallDisorderContent via DisorderPredictor.PredictDisorderRegions; treat confidence as advisory only. The other tools in this family (signal peptide, TM, coiled-coil, domains, motifs, SEG, hydrophobicity) are not guarded.

End-to-end grounded example — "characterize this protein"

Task. Given one protein sequence, (1) map intrinsically disordered regions, (2) test for a signal peptide, (3) find transmembrane helices, (4) call coiled-coils + domains, (5) mask protein low-complexity, (6) profile hydrophobicity to corroborate (1) and (3).

Tool / Method ID chain (MCP names; C# path in parentheses):

1. predict_disorder(sequence, minRegionLength=5) → disorderedRegions (report boundaries + overallDisorderContent; confidence advisory). (DisorderPredictor.PredictDisorder)
2. predict_signal_peptide(proteinSequence, prokaryote=false) → N-terminal signal + cleavage site. (ProteinMotifFinder.PredictSignalPeptide)
3. predict_transmembrane_helices(proteinSequence, threshold=1.6) → TM segments + topology. (ProteinMotifFinder.PredictTransmembraneHelices)
4. predict_coiled_coils(proteinSequence) + find_protein_domains(proteinSequence) → coiled-coil + domain calls. (ProteinMotifFinder.PredictCoiledCoils / .FindDomains)
5. find_protein_low_complexity_regions(proteinSequence) → SEG intervals to down-weight motif hits. (ProteinMotifFinder.FindLowComplexityRegions)
6. hydrophobicity_profile(proteinSequence, windowSize=9) → peaks over TM (step 3), troughs over IDRs (step 1). (SequenceStatistics.CalculateHydrophobicityProfile)

Provenance
1) predict_disorder(sequence, minRegionLength=5) → disorderedRegions [0-based, boundaries validated; confidence advisory], overallDisorderContent
2) predict_signal_peptide(proteinSequence, prokaryote=false) → signal peptide + cleavage site
3) predict_transmembrane_helices(proteinSequence, threshold=1.6) → TM segments + topology
4) predict_coiled_coils(proteinSequence); find_protein_domains(proteinSequence) → coiled-coil + domains
5) find_protein_low_complexity_regions(proteinSequence) → SEG intervals (mask/down-weight)
6) hydrophobicity_profile(proteinSequence, windowSize=9) → peaks corroborate TM (3), troughs corroborate IDRs (1)
Coordinates: 0-based residue indices; regions [start,end] inclusive. Units: normalized scores / bits / kcal-scale KD.
Envelope: DISORDER-REGION-001 — report validated boundaries + overallDisorderContent; confidence uncalibrated (STOP if a validated per-region confidence is required).
Caveat: alpha software; not for clinical use — independently validate before any decision use.

Reference

• Tool map (this family's protein tools, one-liners + Method ID + doc) — the curated index (no generated slice): reference/tool-map.md
• Fuller recipes + parameter guidance + envelope STOP rule: reference/pipelines.md
• Algorithm background (invariants/formulas — link, don't copy): Disorder_Prediction.md · Disordered_Region_Detection.md · MoRF_Prediction.md · Signal_Peptide_Prediction.md · Transmembrane_Helix_Prediction.md · Coiled_Coil_Prediction.md · Domain_Prediction.md · PROSITE_Pattern_Matching.md · Low_Complexity_Region_Detection.md
• Operating envelope / guarded units: LIMITATIONS.md (DISORDER-REGION-001).
• Cross-cutting: bio-rigor (rigor guardrail) · seqeron-discovery (tool lookup) · bio-annotation (DNA-shaped annotation & DNA motifs — overlap boundary above).