「nes」の検索結果

Identify direct miRNA-target interactions from AGO HITS-CLIP, AGO-CLEAR-CLIP (chimeric reads), HEAP (Halo-Ago2 mouse), chimeric eCLIP / miR-eCLIP (deep miRNA-target profiling), or CLASH using chimeric-read processing pipelines, seed-pairing analysis, and 3' auxiliary pairing rules. Use when distinguishing direct miRNA targets from indirect, integrating CLIP-derived target maps with TargetScan / miRDB / DIANA predictions, applying canonical 7mer-8mer seed matching with 3' UTR context, or recovering miRNA-mRNA chimeras at scale.

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Profiles RNA-binding protein targets without antibody or UV crosslinking using STAMP (APOBEC1-RBP fusion, C-to-U editing), scSTAMP (single-cell), TRIBE/HyperTRIBE (ADAR-RBP, A-to-I editing), DART-seq (APOBEC1-YTH for m6A), or Bullseye/SAILOR edit-site detection pipelines. Use when antibody is unavailable or specificity is doubtful, when single-cell RBP profiling is needed (scSTAMP), or when in vivo RBP profiling without UV is preferred.

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Build and analyze pangenomes for prokaryotes (Panaroo, PPanGGOLiN, PEPPAN, GET_HOMOLOGUES, anvi'o pangenomics) and eukaryotes (Minigraph-Cactus, PGGB, vg pangenome graphs). Implement Tettelin core/accessory/cloud genome decomposition (Tettelin 2005), Heap's law open/closed pangenome modeling, gene presence/absence GWAS (Scoary, pyseer), pangenome graph variant calling (vg, PanGenie), and structural-variation graph indexing. Use when assembling species- or genus-level pan-gene catalogs, separating core from accessory/shell/cloud genes, testing gene-content associations with phenotypes, building pangenome graphs from haplotype-resolved assemblies, calling SVs from pangenome graphs, or selecting between bacterial-pangenome and eukaryotic-pangenome workflows.

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Calculates tumor mutational burden from WES/WGS/panel data with Friends of Cancer Research harmonization equations, per-assay calibration (FDA 10/Mb = 7.8 TSO500 = 8.4 OncomineTML), synonymous/indel/germline filtering, hypermutator tiering, blood TMB, and integration with HLA-LOH and neoantigen quality (Luksza 2017 fitness). Use when assessing ICI eligibility under tumor-specific cutoffs (McGrail 2021), comparing tissue vs bTMB, or auditing TMB-H reporting against ESMO 2024 and FDA pembrolizumab pan-tumor 2020.

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Project gene annotations across genomes using TOGA (Kirilenko 2023 whole-genome-alignment chain-based projection with intactness classification), CESAR 2.0 (Sharma & Hiller 2017 codon-aware exon projection), LiftOff (Shumate & Salzberg 2020 reference-based annotation transfer), Liftover (UCSC), GeMoMa (Keilwagen 2019 evidence-based projection), and Comparative Annotation Toolkit (CAT). Use when transferring annotations from a well-annotated reference to query genome(s), classifying gene-loss vs gene-intact across many genomes at scale, building Zoonomia-style comparative annotations across hundreds of mammals or birds (Kirilenko 2023), detecting pseudogenization, projecting alternative isoforms, or selecting between WGA-anchored (TOGA) vs ortholog-based (LiftOff) annotation transfer strategies.

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Queries gnomAD v4 (807k samples), v3, v2.1.1, and constraint metrics with grpmax FAF95, bottleneck-group exclusion, LOEUF interpretation, SV/CNV/mtDNA catalogs, and Whiffin max-credible-AF framework. Use when filtering rare variants, applying ACMG BS1/BA1, ranking genes by LoF intolerance, or selecting between v2 (GRCh37 + chrX/Y constraint) and v4 (GRCh38 + 807k samples).

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Detect syntenic blocks and structural rearrangements between genomes using MCScanX (Wang 2012), JCVI/MCScan (Tang 2008 Python), GENESPACE (Lovell 2022) for orthology-anchored riparian visualization, SyRI for structural variation, AnchorWave for sequence-level synteny, i-ADHoRe 3.0 for highly diverged species, SynNet for synteny networks, and ntSynt for multi-genome macrosynteny. Use when identifying collinear gene blocks across species, distinguishing macrosynteny from microsynteny, detecting inversions/translocations/duplications, anchoring orthology in WGD lineages, producing publication riparian plots, computing synteny block age via Ks (cross-references whole-genome-duplication), or running synteny-aware ortholog inference in polyploids.

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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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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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Performs retrosynthetic planning using AiZynthFinder (MCTS, template-based), Chemformer (template-free transformer), ASKCOS, and emerging RetroSynFormer with explicit handling of route scoring, building-block availability (eMolecules, Enamine, Mcule), forward prediction validation (Molecular Transformer), and disconnection-aware multi-objective search (MO-MCTS). Use when assessing synthetic feasibility of generated or selected molecules, planning multi-step syntheses, building synthesis-aware design pipelines, or screening libraries for retro-route feasibility.

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Trains and applies base-resolution deep learning models on ChIP-seq / ChIP-nexus / CUT&RUN data. Uses BPNet (Avsec 2021 Nat Genet 53:354; soft motif syntax from ChIP-nexus), chromBPNet (Pampari A et al 2025 Nat Genet; bias-factorized base-resolution profiles), EnFormer (Avsec 2021 Nat Methods 18:1196; 196 kb input, ~100 kb effective receptive field), DeepSEA (Zhou 2015; multi-task CNN), and JASPAR 2026 deep-learning collection (1259 BPNet ChIP models). Performs in silico mutagenesis for variant-effect prediction, DeepLIFT/Grad attribution, and TF-MoDISco motif discovery from attribution scores. Use when predicting variant effects on TF binding, discovering soft motif syntax / cooperativity, integrating ChIP-seq with sequence-only predictions, or applying precomputed JASPAR Deep Learning models to new variants.

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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. Filters AI-docking outputs (DiffDock, EquiBind, NeuralPLexer) where ~50% of poses fail physical-validity tests. Use when QC-ing docking results, comparing classical vs ML docking outputs, or filtering pose lists before SAR analysis.

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Identifies super-enhancers from H3K27ac, MED1, or BRD4 ChIP-seq using ROSE, ROSE2, LILY, HOMER -style super, and ENCODE dELS cross-referencing. Handles peak stitching parameters, ranking choices, hockey-stick inflection, marker choice (H3K27ac vs MED1/BRD4), and cross-condition comparison with spike-in normalization. Constructs core regulatory circuitry (Saint-Andre 2016) from SE-encoded TFs. Use when identifying cell-identity / cancer-associated regulatory domains, comparing super-enhancers between conditions, identifying master transcription factor networks, or predicting BET-inhibitor responsiveness.

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Performs gene-level association from GWAS summary statistics via genetically predicted tissue expression using FUSION, PrediXcan, S-PrediXcan, S-MultiXcan, UTMOST, MOSTWAS, kTWAS, EpiXcan, TIGAR-V2, and probabilistic fine-mapping with FOCUS and MA-FOCUS. Use when running TWAS from GWAS sumstats, prioritising candidate causal genes from a GWAS lead locus, picking single-tissue vs cross-tissue models, identifying LD-induced TWAS false positives, choosing ancestry-matched prediction weights, fine-mapping co-regulated TWAS hits, or triangulating TWAS with cis-eQTL Mendelian randomization and colocalization to nominate a causal gene.

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Map nucleosome center positions, occupancy, and fuzziness from ATAC-seq fragment-size patterns using NucleoATAC, ATACseqQC, DANPOS3, or scprinter. Use when characterizing nucleosome organization at promoters and enhancers, calling +1/-1 nucleosomes flanking NFRs, generating V-plots for chromatin structure visualization, or comparing nucleosome positioning between conditions.

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Analyzes alternative splicing at single-cell resolution. The first decision is library chemistry — 10X 3' is fundamentally limited (RT primes from poly-A, R2 falls in 3' UTR, <0.1 junction read per cell per AS event). Plate-based full-length methods (Smart-seq3, FLASH-seq, VASA-seq, STORM-seq) and single-cell long-read (MAS-Iso-seq, scISOr-Seq2) are the chemistries that give per-cell isoform structure. Tools include MARVEL (R, Smart-seq integrated), BRIE2 (Bayesian PSI with regulatory features and ELBO_gain test), scQuint (junction-cluster, plate-based; not for 10X), SpliZ (annotation-free Z-score), Psix (graph-smoothness regulated AS), and Sierra (alternative polyadenylation, often confused with AS). Use when analyzing isoform usage in scRNA-seq, identifying cell-type-specific splicing, or determining whether scRNA-seq chemistry supports splicing analysis at all.

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Assesses RNA-seq data quality specifically for alternative splicing analysis. QC layers include experimental design audit (library prep, read length, depth, replicates), STAR 2-pass cohort-style alignment, junction saturation curves and discovery plateau detection, novel-vs-known junction ratio diagnostics, junction-overhang distribution, splice-site strength scoring (MaxEntScan intrinsic + SpliceAI context-aware), strandedness verification, GENCODE basic vs comprehensive choice, and rRNA contamination screening. Splicing analysis is more demanding than DGE on read length, depth, library prep, alignment strategy, and annotation choice — failures silently bias PSI estimates and inflate novel-junction false positives. Use when evaluating data suitability for splicing analysis, troubleshooting low event detection, or designing sequencing experiments where AS is a primary endpoint.

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Predict enhancer-gene regulatory connections from ATAC-seq using ABC, ENCODE-rE2G, HiChIP, or Cicero. Use when linking distal enhancers to target genes, choosing between contact-aware (ABC, ENCODE-rE2G), accessibility-only (Cicero), and orthogonal (HiChIP H3K27ac, EpiMap) approaches, validating predictions against CRISPRi-FlowFISH gold-standard, or building cell-type-specific regulatory maps for fine-mapping or therapeutic target discovery.

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Use this skill when the user asks how to build + manage direct shipper relationships — moving from spot market to dedicated lanes, customer scoring + credit assessment, contract terms, dedicated capacity agreements, KPI reporting, and how to handle customer disputes. Reference standard customer-carrier contract terms.

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Use when a carrier asks about trailer types — dry van, reefer, flatbed, step-deck, conestoga, tanker, dump, lowboy, intermodal chassis, auto-hauler. Covers length / weight rules, common specs, reefer unit options (Carrier vs Thermo King), liftgate options, kingpin setting, and trailer-to-tractor matching.

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Use this skill when the user asks about passenger-carrying CMVs — buses, motorcoaches, charter operations, school buses, limousines, shuttle services. Covers different HOS rules (10-hour driving / 15-hour on-duty / no 34-restart), Class C CDL with P endorsement, S endorsement for school bus, FMCSA Hours-of-Service for passenger vehicles, $5M insurance minimum, BMC-32 filing, accessibility requirements, and how passenger ops differ from property. Cite 49 CFR 395.5 + 387.33.

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Use this skill when the user asks specifically about preparing for the New Entrant Safety Audit (NESA) under 49 CFR 385 Subpart D — different from a Compliance Review. Covers what auditors look at, the 18-month window, automatic failure conditions, the 60-day fix window, what to NOT do, and how to convert from "new entrant" to permanent authority. Cite 49 CFR 385.301-321.

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Use this skill when the user asks about US-Mexico cross-border CMV operations — long-haul cross-border program, B-1 visas for Mexican drivers, FMCSA OP-1(MX) authority, US-Mexico border commercial zones, USMCA / NAFTA implications, customs brokerage (C-TPAT, FAST), and how a US carrier handles cross-border loads. Reference 49 CFR 365.501-507.

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Use this skill to differentiate IFTA (fuel tax) and IRP (apportioned registration). Covers what each is for, deadlines, and how they interact.

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