「mandatory」の検索結果

Detects somatic mutations in circulating tumor DNA, treating low-VAF detection as a signal-versus-noise problem set by error suppression and molecules sampled, not by the choice of caller. Distinguishes de novo CALLING (scanning a panel for unknown variants, bounded by per-locus error and multiple testing) from tumor-informed DETECTION (tracking a pre-specified variant set, where panel integration reaches single-ppm). Covers VarDict and Mutect2 for de novo calling, UMI-aware callers, and a pysam-based known-variant VAF tracker, with matched-WBC subtraction as the mandatory defense against clonal hematopoiesis (the dominant false positive). Use when calling or tracking tumor mutations from plasma cfDNA, setting a VAF threshold, or deciding whether a low-VAF call is tumor versus CHIP.

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Extracts cfDNA fragmentomics features (DELFI genome-wide short/long ratios, WPS nucleosome positioning, Griffin GC-corrected accessibility profiles, end-motifs/MDS, OCF) for cancer detection and tissue-of-origin from plasma WGS. Centers on the nuclease-footprint reframe (every feature re-reads one nucleosome object), the mandatory GC correction, and the cross-protocol non-comparability that breaks naive classifiers. Runs FinaleToolkit (real CLI/Python, MIT) and the Griffin Snakemake pipeline; DELFI is a method, not a package. Use when deriving fragment-based signal from cfDNA, choosing a feature family for detection vs subtyping, or diagnosing why a fragmentomic model failed validation.

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Designs donor/repair templates for precise CRISPR knock-ins -- choosing the format (ssODN, long-ssDNA/Easi-CRISPR, dsDNA/plasmid, AAV6), sizing homology arms, placing the cut within ~10 bp of the edit, and adding a mandatory codon-checked blocking (PAM/seed) mutation so the edited allele is not re-cut. Frames the HDR-vs-NHEJ-vs-MMEJ pathway competition, the MMEJ (PITCh) and homology-independent (HITI/HMEJ) alternatives for post-mitotic cells, ssODN strand/asymmetry choice, phosphorothioate end-protection, and ranked HDR enhancers. Use when designing a donor for a point mutation, epitope/fluorophore tag, allele replacement, or knock-in, or when HDR efficiency is low. Guide design and base/prime editing are separate skills.

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Reads, queries, and writes bigWig indexed binary signal tracks (coverage, fold-change, conservation, methylation-rate) with pyBigWig (Python) and the UCSC Kent tools (bedGraphToBigWig, bigWigToBedGraph, bigWigInfo, bigWigSummary, bigWigAverageOverBed) and deepTools (multiBigwigSummary, computeMatrix, bigwigCompare). Covers the central trap that a wide query returns a precomputed zoom-level summary (by default the mean, which annihilates narrow peaks) not per-base data, when exact=True/values() is mandatory, the NaN-not-zero gap-handling fork, choosing mean vs max vs sum vs coverage by biological question, and the sorted-bedGraph plus chrom.sizes build requirement. Use when extracting signal at regions, computing mean signal per gene/peak, building a browser track from bedGraph, comparing tracks, or building TSS/gene-body metaprofiles.

日本語の概要は準備中です。原文の説明を表示しています。

Decides how to preprocess plasma cfDNA sequencing data so the recoverable signal survives - library-prep-aware fragment expectations (dsDNA vs ssDNA/adaptase prep), UMI/duplex consensus with fgbio (ExtractUmisFromBam, GroupReadsByUmi --strategy paired for duplex, CallMolecularConsensusReads vs CallDuplexConsensusReads, FilterConsensusReads min-reads "total s1 s2"), the align->group->consensus->RE-align ordering, and the cfDNA dedup trap where naive coordinate dedup collapses nucleosome-coincident independent molecules. Covers when single-strand consensus suffices vs when duplex is mandatory, the singleton/sensitivity tax at low input, and reading the insert-size histogram as a pre-analytical QC instrument. Use when processing plasma cfDNA reads before fragmentomics, ctDNA mutation calling, or tumor-fraction estimation.

日本語の概要は準備中です。原文の説明を表示しています。

Detects and removes contamination in genome assemblies via two disjoint workflows - foreign-sequence screening of a single-organism (eukaryote/isolate) assembly with NCBI FCS-GX (GenBank-submission-mandatory), FCS-adaptor, and BlobToolKit blob plots; and MAG/bin quality assessment with CheckM2 plus GUNC (chimerism) plus GTDB-Tk taxonomy, judged against MIMAG. Covers why CheckM2 alone is blind to disjoint-marker chimeras, the FCS-GX RAM wall, organelle/NUMT triage, strain heterogeneity, and the HGT-vs-contamination (tardigrade) trap. Use when screening an assembly for foreign contamination before GenBank submission, assessing MAG completeness/contamination/chimerism, deciding which contigs to remove, or distinguishing real HGT from contaminant contigs.

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Bead-based signal normalization and cross-batch harmonization for CyTOF and high-parameter cytometry - EQ four-element bead normalization of instrument sensitivity drift (CATALYST normCytof, premessa), and reference-anchor cross-batch normalization (CytoNorm, per-cluster quantile splines). Covers the distinction between within-run drift correction and between-batch correction, the mandatory anchor/reference sample, why normalization is per-cluster with many quantiles, and the over-correction risk. Use when correcting CyTOF signal drift, harmonizing multi-batch or multi-site studies, or deciding whether to normalize data versus model batch in the design.

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Tests genotype-environment associations and identifies adaptive loci while correcting for the four-confound landscape (structure, demography, background selection, sampling design) using LFMM2 with mandatory K via sNMF cross-entropy elbow (LEA 3), BayPass Core/AUX/C2/IS with Omega covariance matrix, RDA / pRDA for polygenic adaptation (Forester 2018; requires imputed genotypes), OutFLANK with trimmed FST null, pcadapt, gradient forests (Ellis-Smith-Pitcher 2012, NOT mis-cited Ellis-Manel), Capblancq & Forester 2021 RDA Swiss-army-knife, genomic-offset prediction with Lind & Lotterhos 2025 three-regime caveat, Lotterhos-Whitlock sampling optima, Wang & Bradburd 2014 IBD vs IBE, and Circuitscape + ResistanceGA. Use when identifying adaptive loci across gradients, choosing K for LFMM2, deciding among GEA methods, predicting maladaptation with the novel-environment caveat, distinguishing IBD vs IBE, or optimizing sampling design.

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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.

日本語の概要は準備中です。原文の説明を表示しています。

Predicts protein-coding gene structures (exons, introns, UTRs) in eukaryotic genomes with BRAKER3 (RNA-seq + protein evidence), BRAKER1/BRAKER2, GALBA (protein-only), Funannotate (fungi), GeMoMa (homology projection), or Helixer/Tiberius (deep-learning ab initio). Covers the evidence-first tool decision, mandatory soft-masking, the training-set-quality-dominates principle, OrthoDB clade-partition selection, the one-isoform-per-locus and missing-UTR traps, merge/split errors, and reference bias against orphan genes. Use when annotating a newly assembled eukaryotic genome, choosing a gene-prediction pipeline based on available evidence, or diagnosing a poor annotation.

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Quantifies biodiversity from species abundance/incidence tables using Hill numbers (iNEXT) with coverage-based rarefaction-extrapolation (Chao & Jost 2012), asymptotic richness via Chao1/ACE/jackknife as a lower bound, Baselga turnover/nestedness partition with the Podani alternative as sensitivity check, mandatory Hellinger transformation before ordination (Legendre & Gallagher 2001), Faith PD and SES_MPD/SES_MNTD with explicit null-model choice, and Maire 2015 functional-diversity dimensionality optimization. Use when comparing diversity across sites with unequal sampling effort, picking the right richness estimator for singleton-heavy amplicon data, partitioning beta diversity into turnover vs nestedness, reporting Hill-number effective species counts rather than raw entropies, computing SES_MPD with explicit null-model justification, or deciding whether to apply standard metrics to compositional amplicon data. Not for clinical 16S microbiome diversity (see microbiome/diversity-analysis).

日本語の概要は準備中です。原文の説明を表示しています。

Call protein-RNA binding sites from CLIP-seq BAM with CLIPper, PureCLIP, Skipper, Piranha, omniCLIP, CTK, CLAM, or Paraclu. Use when choosing between coverage-based, HMM-based, beta-binomial window-based, and crosslink-site-based peak callers; applying ENCODE eCLIP thresholds (log2 IP/SMInput >= 3, -log10 p >= 3); deciding when SMInput is mandatory; or reconciling peak-set discordance between callers for the same RBP.

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Detects allele-specific transcription factor or histone modification binding from heterozygous-variant ChIP-seq using WASP (reference-bias filter; mandatory upstream), RASQUAL (joint QTL + bias-corrected testing), BaalChIP (Bayesian beta-binomial with copy-number-aware overdispersion), and AlleleSeq (personalized diploid genome). Handles imprinted-locus awareness, X-inactivation artifacts, cancer copy-number imbalance, and integration with downstream caQTL / bQTL mapping. Use when identifying variants with allelic effects on TF binding, fine-mapping causal regulatory variants, validating deep-learning variant predictions, or characterizing cis-acting regulatory effects.

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MANDATORY for every coding agent (Claude Code, Codex, or any other) — keep this repository's documentation in sync after any change to behavior, configuration, interfaces, events, schema, or features. Use automatically at the end of change-sets that alter an env var, event type, hook or state behavior, API, schema, WebSocket message, MCP tool, CLI command, or user-facing feature, and whenever the user asks to update documentation.

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MANDATORY for every coding agent and contributor touching localized content — keep all five localization surfaces (dashboard UI keys, wiki page, full mirrored guides, locale-aware formatting, language switchers) in parity across every supported language. Use automatically (without being asked) whenever you add or change user-visible UI copy, add an i18n key, edit README-EN.md or a localized guide, edit wiki/index.html, or add a language surface.

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MANDATORY for every coding agent (Claude Code, Codex, or any other) on every change-set — every applicable source file the agent creates or updates MUST start with the project's copyright/authorship header (file overview + exact author line). Use automatically whenever writing a new file or editing an existing one; do not wait to be asked. Covers JS/TS/TSX/CJS/MJS, Python, shell, and CSS. Includes the audit script to verify repo-wide compliance.

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Mandatory operating rules for ANY task involving KiCAD projects. Loaded when the user mentions KiCAD, schematics, PCBs, or any .kicad_* file. Prevents file corruption by routing all changes through Konnect MCP tools.

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Expert EU Cyber Resilience Act (CRA) advisor for Regulation (EU) 2024/2847 — mandatory cybersecurity and vulnerability handling requirements for all products with digital elements (PDEs) sold in the EU. Use this skill for gap analysis, product classification (Default / Class I / Class II), conformity assessment route selection, CE marking, SBOM requirements, vulnerability and incident reporting to ENISA/CSIRTs, support period obligations, and manufacturer/importer/distributor duties. Trigger for EU CRA, Cyber Resilience Act, PDE compliance, Annex I requirements, SBOM EU, CE marking cybersecurity, or connected product security EU.

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Expert TISAX (Trusted Information Security Assessment Exchange) advisor for the automotive supply chain — the ENX/VDA assessment regime that OEMs like VW, BMW, and Mercedes-Benz require from suppliers and service providers. Covers the VDA ISA 6 catalogue (current through 2026) and the ISA2027 transition (published July 1, 2026; mandatory for assessments ordered from January 1, 2027), assessment levels AL1/AL2/AL3, all 12 assessment objectives/labels (Confidential, Strictly Confidential, High/Very High Availability, Proto Parts/Vehicles, Test Vehicles, Proto Events, Data, Special Data), maturity scoring (0–5, target 3, cutback rules), the ENX portal process, scoping, audit-provider selection, corrective action plans and the 9-month window, 3-year label validity, and ISO 27001 mapping. Use for any TISAX, VDA ISA, ENX, automotive information-security assessment, prototype protection, or OEM supplier-security requirement question — gap assessments, label selection, readiness, and audit prep.

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Pick the right LLM for LEGAL TRANSLATION — translating contracts, statutes, case law, and legal correspondence across languages, including Arabic/MENA. Vendor-neutral routing triangulated from mid-2026 evidence (WMT25 human eval, SwiLTra-Bench legal-MT, multilingual-reasoning proxies, ArabLegalEval). There is NO clean legal-translation leaderboard, so this vertical is directional and treats human legal-linguist review as mandatory. Asks up to 4 quick questions (language pair, cost, speed, privacy/certification), then recommends a primary model + fallback + what to avoid + what a human must verify. Use when someone asks "which model to translate this contract/statute", "best AI for legal translation", "translate this legal doc to/from Arabic", or is about to machine-translate legal text without a fixed model.

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Generates standalone interactive HTML "deal cards" that translate complex regulations into negotiation-ready reference tools, systematically distinguishing mandatory obligations from negotiable implementation choices. Use when the user needs an interactive regulatory guide for (1) contract negotiation support, (2) client education or internal training, (3) regulatory briefings for commercial stakeholders, or (4) structured comparison between required and flexible compliance paths. Primary focus on EU digital regulation (Data Act, AI Act, CRA, DORA, NIS2, GDPR) but the structural pattern transfers to any regulation where separating hard obligations from implementation choice is the point. Supports bilingual output where the jurisdiction calls for it.

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Performs a legal compliance audit for a Moroccan e-commerce website, focused on personal data protection (Law 09-08) and consumer contract disclosures/obligations (Law 31-08). Use this skill when a user asks to audit, check, or assess the legal compliance of an e-commerce website operating in Morocco — presence and validity of Terms & Conditions, privacy policy, CNDP declaration, mandatory disclosures, right of withdrawal, consent banner. Out of scope: compliance for other countries, Meta/Google advertising compliance (covered by another skill), definitive legal advice (results are a starting point for professional review, not legal advice).

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Use this skill when asked to review, analyze, or draft a contract governed by Icelandic law. Triggers on requests involving Icelandic commercial agreements, consumer contracts, sales agreements, service contracts, or any contract where Icelandic mandatory rules may apply.

日本語の概要は準備中です。原文の説明を表示しています。

Expert EU Cyber Resilience Act (CRA) advisor for Regulation (EU) 2024/2847 — mandatory cybersecurity and vulnerability handling requirements for all products with digital elements (PDEs) sold in the EU. Use this skill for gap analysis, product classification (Default / Class I / Class II), conformity assessment route selection, CE marking, SBOM requirements, vulnerability and incident reporting to ENISA/CSIRTs, support period obligations, and manufacturer/importer/distributor duties. Trigger for EU CRA, Cyber Resilience Act, PDE compliance, Annex I requirements, SBOM EU, CE marking cybersecurity, or connected product security EU.

日本語の概要は準備中です。原文の説明を表示しています。