「validation」の検索結果

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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Discovers, classifies, filters, and quantifies full-length transcript isoforms from PacBio Iso-Seq/Kinnex (HiFi) and Oxford Nanopore (cDNA/direct-RNA) long reads, using the isoseq+pigeon pipeline, SQANTI3, and ONT tools (IsoQuant, FLAIR, Bambu, StringTie2). Covers why a novel isoform is an artifact until proven otherwise (RT template-switching, intra-priming, and 5' degradation manufacture junctions and truncations), the SQANTI3 structural categories and their trust order, the Kinnex skera-split step, orthogonal CAGE/poly-A/short-read-junction validation, and why long-read isoform quantification needs EM. Use when building a full-length isoform catalog, classifying/filtering long-read transcripts, running Iso-Seq or ONT cDNA/dRNA analysis, or judging novel-isoform reliability.

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Infer or annotate TCR antigen specificity by unsupervised clustering (TCRdist/tcrdist3, GLIPH2, clusTCR, GIANA) and database lookup (VDJdb, IEDB, McPAS-TCR), and rank candidates with supervised predictors (ERGO-II, NetTCR-2.x, pMTnet) under explicit caveats. Encodes the central truth that general TCR-epitope prediction for UNSEEN epitopes essentially does not work (collapses to near-random; IMMREP22, Grazioli 2022) because labeled data is dominated by a few immunodominant epitopes and there is no true negative set — so clustering for discovery is the honest task and de-novo binding needs wet-lab validation. Use when annotating TCR specificity or grouping a repertoire. Epitope/MHC context lives in mhc-binding-prediction.

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Handles BED-format genomic intervals (BED3 through BED12, narrowPeak/broadPeak) and the coordinate-system substrate the whole interval category rests on, with bedtools (CLI) and pybedtools/pyranges/pandas (Python). Covers the 0-based half-open vs 1-based-closed convention boundary and the start-1/end-unchanged conversion, the silent failures (chrom-name mismatch, CRLF, lexicographic-vs-version sort under -sorted), genome/chrom.sizes generation, sorting contracts, BED12 block invariants, validation, makewindows, cross-assembly liftover (liftOver/CrossMap), and BED<->VCF/BAM/FASTA conversion. Use when reading, creating, validating, sorting, lifting between genome builds, or converting interval files, preparing inputs for bedtools/tabix/bigBed, or debugging an off-by-one or empty-overlap result.

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Nominates and assesses CRISPR off-target sites genome-wide. Enumerates candidate sites by mismatch and bulge tolerance with Cas-OFFinder/CRISPRitz, ranks them with the published CFD score (SpCas9-only, relative ranker) or MIT/CRISTA/energy models, runs variant-aware screening against gnomAD/individual genomes (CRISPRme), and frames the empirical genome-wide discovery assays (GUIDE-seq, CIRCLE-seq, CHANGE-seq, DISCOVER-seq, Digenome-seq) and high-fidelity nuclease choice (HiFi Cas9, Sniper-Cas9, eSpCas9, SpCas9-HF1). Use when assessing guide RNA specificity, choosing among candidate guides, screening a therapeutic guide against population variation, or planning empirical off-target validation. Distinguishes predicted vs detected vs validated. On-target activity scoring and deaminase (Cas-independent) base/prime-editor off-targets are separate skills.

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Transfers gene annotations between genome assemblies via coordinate liftover (UCSC liftOver, CrossMap for same-species version updates) or feature/sequence projection (Liftoff for same/close species, miniprot for protein-level cross-species, TOGA/GeMoMa/CAT for distant clades). Covers the coordinate-vs-projection decision by divergence, why a successful lift is not biological confirmation, reference bias, the silent-dropping of unmapped features, build/PAR/MHC/inversion hazards, and transfer-vs-de-novo validation. Use when annotating a new assembly of a species with an existing reference, harmonizing coordinates across builds, or mapping annotations across related species.

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Identifies differential m6A methylation between conditions from MeRIP-seq paired IP/input data using exomePeak2 (GC-bias-aware differential via its bam_ip/bam_input control + bam_treated_ip/bam_treated_input treatment arms), QNB beta-binomial, MeTDiff HMM, and RADAR, plus the paired-symmetric edgeR/DESeq2-on-peak-counts route when batch/lot covariates need fixed-effect handling that exomePeak2's API does not accept. Covers paired vs unpaired vs interaction designs, batch confounding and per-lot meta-analysis, the stoichiometry-vs-expression-vs-IP-efficiency confound, and effect-size filtering against under-powered N=2 designs. Use when comparing m6A across two or more conditions, choosing between exomePeak2/QNB/RADAR/MeTDiff for a design, handling batch confounding when exomePeak2's API is too rigid, distinguishing real hyper/hypo-methylation from expression shifts, applying effect-size thresholds, or planning orthogonal stoichiometry validation (GLORI/SAC-seq/m6Anet mod_ratio).

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Calls m6A peaks from MeRIP-seq / m6A-seq paired IP-vs-input data using exomePeak2 (transcript-aware, GC-bias-corrected Poisson GLM), MeTPeak (HMM over sliding windows), MACS3/MACS2 with --nomodel --broad --keep-dup all (genome-wide broad alternative), and DRACH motif enrichment via HOMER or ggseqlogo as a sanity check (NOT a filter). Covers BED12 vs narrowPeak output, exonic vs intronic peak handling, multi-tool reconciliation (intersection vs union), the m6A-vs-m6Am ambiguity at 5'UTR peaks that antibody methods cannot resolve, and orthogonal validation (miCLIP/GLORI/m6A-SAC-seq/m6Anet). Use when calling peaks from paired IP/input genome BAMs, choosing exomePeak2 (transcript-aware default) vs MACS3 (broad genomic) vs MeTPeak (HMM-smoothed low-coverage), confirming DRACH enrichment as a sanity check on the peak set, reconciling differing peak sets across tools, validating MeRIP peaks against single-base methods, interpreting 5' peaks where m6Am contamination is possible, or recommending a consensus strategy.

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Simulate transcription factor perturbation effects on cell state in silico with CellOracle and Dynamo, and predict transcriptional responses to genetic perturbations with GEARS, scGen, and CPA. Covers the direction-not-magnitude principle, local-linear validity, the GRN/velocity error it inherits, baseline discipline (mean and additive baselines), and the validation gap. Use when predicting TF knockout or overexpression effects, ranking driver TFs for fate transitions, or planning perturbation experiments. For GRN construction see multiomics-grn; for experimental Perturb-seq see single-cell/perturb-seq.

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Designs and analyzes pooled prime-editor (PE) screens for installing precise genetic variants without bystander confounding. Covers pegRNA design with PRIDICT and PRIDICT2 for predicting per-pegRNA editing efficiency, pegRNA architecture (spacer + scaffold + PBS + RTT), PE2/PE3/PE3b/PEmax variants, MOSAIC in situ saturation mutagenesis, the PRIME pooled-screen methodology (Ren 2023; ~3,699 ClinVar variant screens), chromatin context as a major locus-level determinant of PE efficiency, scaffold-incorporation and indel byproduct quantification with CRISPResso2, and the cross-modal validation strategy of PE + base-editor screens for variant function. Use when designing a pegRNA library for variant installation, choosing between BE and PE for a specific edit, predicting pegRNA efficiency before library synthesis, analyzing PE screen output, distinguishing intended-edit from scaffold-incorporation, or scaling PE screens to thousands of variants.

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Discover RBP binding motifs from CLIP-seq peaks or single-nucleotide crosslink sites using HOMER, MEME/STREME, kpLogo, mCross (CL-position-registered motifs), PEKA (positional k-mer enrichment), RBPamp (affinity), and RNA Bind-n-Seq (RBNS) cross-validation. Use when characterizing RBP sequence specificity, registering motifs to crosslink positions, validating in vivo CLIP motifs against in vitro RBNS Kd, reconciling motif disagreements across tools, or correcting for the uracil crosslinking bias that contaminates raw CLIP motif logos.

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Cross-method decision tree for calling hits in pooled CRISPR screens. Catalogs statistical models (MAGeCK RRA, MAGeCK MLE, BAGEL2, drugZ, JACKS, Chronos, CERES), experimental designs each is built for, failure modes outside design domain, reconciliation when methods disagree, multiple-testing and effect-size thresholds, the order of operations (count -> QC -> CN-correct -> hit-call -> validate), the second-best-sgRNA conservative rule, and consensus-hit strategy. Use when choosing among MAGeCK / BAGEL2 / drugZ / JACKS / Chronos for a given design, reconciling disagreement across two or three methods on the same screen, deciding whether to require consensus, gating downstream validation by hit-confidence tier, or interpreting unstable hit lists across reruns.

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Analyzes base-editing screens for variant function. Covers library design (Hanna 2021 ClinVar-scale CBE screen benchmarked on BRCA1/2, Cuella-Martin 2021 DDR saturation), CBE vs ABE chemistry choice (BE3/BE4 vs ABE7.10/ABE8.20/ABE8e), editing-window math (positions 4-8 from PAM-distal end; 4-7 for ABE7.10), bystander-edit quantification and the variant-call ambiguity it creates, sgRNA-efficiency filtering before hit calling, indel byproduct interpretation, the substitution-vs-indel diagnostic, variant annotation against ClinVar / COSMIC, and the Broad be-validation-pipeline. Use when designing a BE variant screen, choosing CBE vs ABE for a specific edit, interpreting bystander-confounded hits, distinguishing functional signal from indel artifact, integrating CRISPResso2 output with screen scoring, or deciding BE vs PE for SNV installation.

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Reads, validates, and prepares CDISC SDTM and ADaM clinical trial data for analysis. Covers SDTM domain joins (DM, AE, EX, VS, LB, DS), ADaM architecture (ADSL, BDS, OCCDS, ADTTE) with traceability, treatment-emergent AE conventions, baseline derivation, SUPPQUAL/NSV handling, Define-XML 2.1, and Pinnacle 21 / CORE validation. Use when working with clinical trial datasets in CDISC SDTM/ADaM format, preparing analysis-ready data, or validating for regulatory submission.

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Validates docked / generated protein-ligand poses using PoseBusters physical-validity tests, strain energy quantification, geometric checks (planarity, vdW overlap, bond/angle distortion), and pose-energy reasonableness. Use when QC-ing docking results, comparing classical vs ML docking outputs, or filtering pose lists before SAR analysis.

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Builds QSAR / QSPR models using chemprop D-MPNN, MolFormer, Uni-Mol, ChemBERTa, random forest baselines, and Gaussian processes with explicit handling of OECD 5 principles, applicability domain (kNN, leverage, conformal prediction, Mahalanobis), scaffold-balanced splits, ensemble uncertainty, calibration (Platt, isotonic), feature importance (SHAP, atomic attribution), and prospective validation. Use when building target-specific predictive models from in-house bioassay data, ADMET endpoints, or selectivity profiles.

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Enumerates virtual chemical libraries via reaction SMARTS transformations using RDKit and reaction templates, with explicit handling of atom mapping, RDChiral template extraction, product validation, RECAP/BRICS fragmentation, R-group decomposition, matched molecular pair analysis (MMPA), and Free-Wilson analysis. Use when generating combinatorial libraries from building blocks, enumerating analog series, deriving structure-activity rules, or extracting transformations from reaction data.

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Performs alchemical free-energy calculations including relative binding free energy (RBFE / FEP+) and absolute binding free energy (ABFE) via OpenFE, FEP+, GROMACS, AMBER pmemd, and OpenMM with explicit lambda scheduling, soft-core potentials, MBAR/BAR analysis, cycle-closure validation, and protocol-appropriate enhanced sampling. Compares ML alternatives (Boltz-2 affinity, DeepDock). Use when ranking analogs by binding affinity beyond docking accuracy, performing prospective lead optimization, or validating SAR predictions.

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Runs cis-pQTL Mendelian randomization for drug-target validation using UKB-PPP (Olink), deCODE (SomaScan), Fenland, INTERVAL, ARIC, and FinnGen-PPP proteomes plus colocalization triangulation, phenome-wide on-target adverse-effect scans, cross-platform Olink/SomaScan replication, and PAV (protein-altering variant) sensitivity. Use when nominating or de-risking a drug target from plasma-proteome GWAS, mimicking pharmacological inhibition via cis-pQTL instruments, separating shared-causal from LD-confounded signal under the Schmidt 2020 cis-MR framework, screening on-target adverse phenotypes pheWAS-style, or producing publication-grade STROBE-MR plus PP.H4 evidence for a target gene.

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Validate alignment quality with insert size distribution, proper pairing rates, GC bias, strand balance, and other post-alignment metrics. Use when verifying alignment data quality before variant calling or quantification.

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Use when the user mentions simulator testing, visual verification, push notification testing, location simulation, screenshot capture, OR live accessibility validation (VoiceOver announcements, Dynamic Type, ADA checks) on the simulator.

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Use when the user mentions App Store screenshot validation, screenshot review, checking screenshots before submission, or verifying screenshot dimensions and content.

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Build SwiftUI layouts using stacks, grids, lists, scroll views, forms, and controls. Covers VStack/HStack/ZStack, LazyVGrid/LazyHGrid, List with sections and swipe actions, ScrollView with ScrollPosition and scroll-driven reveal surfaces, Form with validation, Toggle/Picker/Slider, .searchable, and overlay patterns. Use when building data-driven layouts, collection views, paged detail reveals, settings screens, search interfaces, or transient overlay UI.

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Implement iOS authentication flows with AuthenticationServices and LocalAuthentication. Use when building Sign in with Apple, passkey/WebAuthn registration or sign-in with ASAuthorizationPlatformPublicKeyCredentialProvider, ASAuthorizationController credential state and revocation handling, ASWebAuthenticationSession OAuth or third-party login, Password AutoFill, identity-token server validation, or local biometric re-authentication with LAContext.

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