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Render a 'brand identity reveal' video from a config — a single poster frame in a real, softly-lit space (real wall, soft-focus plant in the corner, dappled leaf shadow, illuminated poster) whose artwork HARD-CUTS through ~10 on-brand poster mockups (hero product, IG post, hanging banners, sticker sheet, logo lockup, poster, two lifestyle stills, packaging, big icon) then holds on a brand end card. The environment plate is one create-image-fal generation; the mockups are real-DOM HTML frame-stepped via Playwright, perspective-composited into the detected frame quad with the plate's real leaf-shadow multiplied back onto each poster (reads as behind glass), sequenced by FFmpeg. Deterministic assembly, FREE (the plate comes from create-image-fal, the bed from create-music-elevenlabs), music bed only and approved brand copy only. Use for the brand-identity-reveal format.

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Use when a Simulink model is incompatible with Simulink Design Verifier (sldvcompat returns false, or an SLDV analysis errors out on an unsupported construct) and needs to be made analyzable. Diagnoses the incompatibility, applies the matching fix to a copy, and confirms the copy is compatible; optionally raises confidence the fix preserved behavior via a back-to-back consistency replay (agreement on the generated tests, not a proof of equivalence). Do NOT use for running test generation, design error detection, or requirement verification themselves — only for making a model compatible so those can proceed.

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Local vision CLIs: glance (describe/ask/OCR an image), ground (locate a target, pixel box), detect (element inventory), trace (image to SVG geometry), crop (cut a pixel box to a file), and scripts/html_shot.py (HTML file to image). Use for any task involving an image — questions, text, splitting and transcribing long screenshots or chat histories, locating elements, comparing, rebuilding as HTML/SVG, digitizing a sketch or diagram, reading values off a chart, operating a GUI from screenshots — and to re-check an image yourself when a description you were given lacks a detail.

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Use Verify for snapshot testing in .NET. Approve API surfaces, HTTP responses, rendered emails, and serialized outputs. Detect unintended changes through human-reviewed baseline files.

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Use Slopwatch to detect LLM reward hacking in .NET code changes. Run after every code modification to catch disabled tests, suppressed warnings, empty catch blocks, and other shortcuts that mask real problems.

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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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Detects A/B chromatin compartments from balanced Hi-C contact matrices via eigenvector decomposition of the distance-normalized, Pearson-correlated cis matrix with cooltools (eigs_cis), then orients (phases) the compartment eigenvector against a GC or gene-density track so the active (A) sign is not arbitrary. Covers the eigenvector-is-a-choice problem (per-arm view_df to remove the centromere gradient; picking the eigenvector by max correlation with activity, not by eigenvalue), GC phasing with bioframe.frac_gc, resolution choice (100kb-1Mb), saddle plots and saddle_strength for compartmentalization strength, the cohesin-loss-strengthens-compartments result, subcompartments (SNIPER/Calder/dcHiC), and cross-condition compartment switching. Use when calling A/B compartments, computing E1/eigenvectors, phasing the eigenvector, building saddle plots, choosing a compartment resolution, quantifying compartment strength, or comparing compartmentalization across conditions.

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Estimates tumor fraction (the genome-wide proportion of cfDNA molecules that are tumor-derived, the cfDNA analogue of bulk-tumor purity) from shallow whole-genome sequencing with ichorCNA, an HMM over 1 Mb bins that jointly EM-estimates tumor fraction, ploidy, and subclonal prevalence over a normal/ploidy grid. Encodes the load-bearing reframes: tumor fraction is the quantity that travels across assays and is NOT mutation VAF (clonal-het VAF approximately TF/2), CNA-based estimation has a hard ~3 percent limit-of-detection floor, and near-diploid or copy-neutral-LOH genomes return a falsely low value. Selects the estimator by data type (sWGS to ichorCNA, deep panel to max-VAF, methylation to deconvolution, sub-3 percent to fragmentomics or methylation). Use when quantifying tumor burden from a liquid biopsy, picking a tumor-fraction estimator for a given assay, or reconciling a TF estimate against a panel VAF.

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Calls germline small variants (SNPs and indels) from Oxford Nanopore and PacBio HiFi long reads with Clair3, a two-stage (pileup + full-alignment) deep-learning caller, selecting the chemistry- and basecaller-version-matched model, enabling read-based phasing, and benchmarking against GIAB with stratification. Covers why the model string is the experiment (no auto-detection, silent degradation on mismatch), why ONT homopolymer/STR indels are the residual error whole-genome F1 hides, and the somatic/trio/RNA boundary to the ClairS/Clair3-Trio family. Use when calling germline SNVs/indels from ONT or HiFi BAMs, choosing a Clair3 model, phasing variants, or benchmarking long-read calls.

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Assesses genetic health of populations for conservation with Ne estimation across time horizons (LDNe NeEstimator V2 option-file API + SNeP physical-linkage correction; recent trajectory via GONE/GONE2; deep history via Stairway Plot 2 / dadi / fastsimcoal2 / PSMC), F-statistics, runs of homozygosity binned by length class to date inbreeding, genetic-load decomposition (Bertorelle 2022 realized vs masked), the modern 100/1000 Ne rule (Frankham 2014), Ne/Nc 2-6 orders of magnitude in marine fish (Hauser & Carvalho 2008), tree-sequence forward simulations (SLiM 4 + pyslim + tskit), and the Sukumaran-Knowles caveat against MSC methods for management-unit definition. Use when estimating Ne by time horizon, detecting inbreeding via F_ROH, decomposing genetic load, justifying conservation thresholds, distinguishing ESU/MU/DPS, configuring NeEstimator V2, or correcting LDNe physical linkage.

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Detects acquired antimicrobial-resistance determinants and chromosomal point-mutation resistance in bacterial assemblies using AMRFinderPlus, ResFinder 4.0 (acquired + PointFinder), CARD-RGI, abritAMR, staramr, and species-specific callers (TB-Profiler, Mykrobe). Harmonises cross-tool output via hAMRonization, contextualises determinants with mobile-genetic-element annotation (MOB-suite, PlasmidFinder, MobileElementFinder, ICEberg), predicts phenotype against EUCAST or CLSI breakpoints, and translates calls into WHO GLASS reporting categories. Use when screening clinical or surveillance isolates for AMR, distinguishing acquired vs intrinsic vs point-mutation resistance, calling rpoB / katG / pncA / gyrA / mgrB mutations, reconciling AMRFinderPlus vs RGI vs ResFinder disagreement, contextualising carbapenemases or mcr alleles on plasmids, predicting susceptibility from genotype against the WHO Mtb 2nd-edition catalogue, or building a hAMRonized multi-lab AMR surveillance pipeline.

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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.

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Aligns and QCs methylated-RNA-immunoprecipitation (MeRIP / m6A-seq) IP and input libraries using STAR or HISAT2 splice-aware mapping, samtools sort/index, IP/input matched-pair tracking, antibody-lot metadata recording, replicate concordance via deepTools multiBamSummary + plotCorrelation, IP enrichment QC via plotFingerprint and per-transcript IP/input ratio distributions, library-complexity saturation curves via PreSeq, and the explicit do-NOT-deduplicate convention for standard non-UMI MeRIP. Use when preparing paired IP and input BAM files for exomePeak2 / MeTPeak / MACS3 peak calling, evaluating MeRIP replicate concordance and IP enrichment, deciding whether to deduplicate (standard MeRIP typically NOT), choosing genome-vs-transcriptome alignment for downstream peak vs m6Anet workflows, recording antibody clone and lot metadata for cross-batch reconciliation, detecting failed IPs via saturation curves and IP/input distribution shape, or generating IP-over-Input bigWig tracks for visualisation.

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Designs genomics experiments so technical nuisance variation (batch, lane, plate, flow cell, operator, reagent lot, processing day) is balanced against the biological variable of interest and therefore estimable rather than confounded, using constrained sample-to-batch assignment (designit, OSAT), the confounder/mediator/collider distinction, and the principle that no post-hoc correction recovers a fully confounded design. Covers detecting hidden batches with surrogate variable analysis, a decision table for downstream correction (ComBat-seq, RUVSeq, SVA) whose execution is deferred to differential-expression/batch-correction, and reproducibility metadata. Use when assigning samples to sequencing batches/lanes/plates, avoiding batch-condition confounding, deciding whether a design is salvageable by correction, choosing a correction method, or estimating the number of hidden batches. For the experimental unit, randomization, and blocking concepts see experimental-design/randomization-blocking.

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Quality control for flow, spectral, and mass cytometry - time-based anomaly cleaning (flowAI, flowCut, PeacoQC, flowClean), margin/boundary event removal, signal-drift detection, dead-cell exclusion, CyTOF Gaussian/DNA/event-length checks, instrument calibration/standardization (MESF, CS&T, peak-2), and batch-level outlier flagging. Use when assessing acquisition quality, choosing a cleaning tool, ordering QC relative to compensation, deciding margin removal before density-based steps, or flagging problematic samples before clustering or differential analysis.

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Reads, inspects, and writes Flow Cytometry Standard (FCS) files from conventional, spectral, and mass cytometry (CyTOF), and parses FlowJo/Cytobank/Diva workspaces. Covers FCS 2.0/3.0/3.1/3.2 internals ($PnE linear-vs-log, $DATATYPE, $SPILLOVER vs SPILL vs $COMP, $TIMESTEP), channel/parameter metadata, the silent linearize/truncate defaults, and R (flowCore, flowWorkspace, CytoML) plus Python (FlowKit, readfcs) readers. Use when loading flow or mass cytometry data, mapping detector channels to antibodies, extracting the event matrix, choosing a reader, or bridging FCS to the scanpy/AnnData ecosystem before preprocessing.

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Designs and analyzes in vivo CRISPR screens in animal tumor models, organoids, and immune-cell adoptive transfers. Covers bottleneck math (250x cells/sgRNA requires ~25M cells implanted; impossible for most syngeneic models, forcing focused libraries), focused library design (Manguso 2017 Nature 547:413 immune screen; Chen 2015 tumor screens), CRISPR-StAR intrinsic-control screening (Uijttewaal 2025 Nat Biotechnol 43:1848), clonal-dynamics-limited detection, tumor-explant DNA recovery, syngeneic vs xenograft vs PDX considerations, and the relationship to downstream MAGeCK / drugZ analysis. Use when designing in vivo CRISPR screens for tumor / immune / metastasis biology, choosing focused vs genome-wide for animal models, addressing bottleneck-induced clonal collapse, picking the syngeneic / xenograft / PDX model, integrating in vivo with in vitro results, or applying CRISPR-StAR for animal experiments.

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Quality control for pooled CRISPR screens covering library representation, Gini index, log-skew, replicate Pearson and Spearman concordance, essentialome precision-recall AUC against CEGv2 (Hart 2017), Cas9 cut-toxicity diagnostics, copy-number amplicon detection (Aguirre 2016 / Munoz 2016), bottleneck propagation through plasmid pool, infection, selection, and endpoint stages, MOI verification, and DepMap-style screen-quality scoring. Use when assessing screen quality before hit calling, deciding whether to repeat or rescue a screen, diagnosing low-confidence hits, choosing between MAGeCK / BAGEL2 / Chronos based on quality grade, picking a normalization strategy from QC signatures, or evaluating whether an in-vivo screen retained adequate library complexity.

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Detect distant homologs using profile and structure-aware methods that go beyond standard BLAST. Use when sequence identity falls into the twilight zone (<35% pairwise), when BLAST fails to find homologs that should exist, when working at metagenomic scale (DIAMOND, MMseqs2), or when structure beats sequence (Foldseek). Covers PSI-BLAST (iterative PSSM), jackhmmer (iterative HMM), HHblits/HHsearch (profile-profile), DIAMOND, MMseqs2, and Foldseek (3Di structural alphabet, van Kempen 2024).

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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, Schwede & Hiller 2017 codon-aware exon projection), LiftOff (Shumate & Salzberg 2021 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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Infer orthologous genes and gene families across species using OrthoFinder3 (HOG-based phylogenetic orthology), SonicParanoid2, Broccoli, ProteinOrtho, OMA / FastOMA hierarchical orthologous groups, eggNOG-mapper, JustOrthologs, and TOGA whole-genome-alignment orthology. Use when building single-copy ortholog sets for phylogenomics, classifying co-orthologs and in/out-paralogs after gene duplication, propagating functional annotation via orthology with awareness of the ortholog conjecture, distinguishing speciation from duplication via gene-tree species-tree reconciliation, computing Quest-for-Orthologs benchmark performance, or running synteny-aware ortholog detection in WGD-affected lineages.

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Detect positive (diversifying / episodic / pervasive) selection using codon dN/dS frameworks. Implements PAML codeml site models (M0/M1a/M2a/M7/M8/M8a), branch models, branch-site model A (Zhang 2005), and HyPhy methods (BUSTED, BUSTED-S, BUSTED-MH, BUSTED-PH, MEME, FEL, FUBAR, aBSREL, SLAC, RELAX, GARD, FUBAR-MH). Includes McDonald-Kreitman framework (asymptotic alpha, impMKT, polyDFE, DFE-alpha, GRAPES) for within-species + divergence inference, RERconverge for trait-correlated rate shifts, CSUBST for convergent substitution, and PhyloAcc for accelerated noncoding evolution. Use when testing adaptive evolution at codons, branches, or full gene; running GARD recombination pre-screen; controlling alignment-error and gBGC false positives; reconciling PAML vs HyPhy results; or performing genome-scale selection scans.

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Build whole-genome alignments using Progressive Cactus (Armstrong 2020 reference-free clade-level WGA), Minigraph-Cactus (Hickey 2024 pangenome-aware), LASTZ chain/net (UCSC pipeline), MUMmer4 (Marçais 2018 pairwise), minimap2 -x asm5/10/20 (Li 2018 fast pairwise), AnchorWave (Song 2022 WGD-aware), and Mauve / progressiveMauve (bacterial). Operates the HAL toolkit (Hickey 2013) for downstream extraction including halSynteny, halLiftover, halBranchMutations, and hal2maf. Use when constructing multi-species alignments for comparative-annotation projection (TOGA), synteny detection, conservation analyses (phyloP / PhastCons), or pangenome graph construction; selecting between reference-free (Cactus) and reference-anchored (LASTZ chains/nets) approaches; tuning sensitivity for closely vs distantly related genomes; or producing HAL files for genome-wide downstream tools.

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Detect, date, and contextualize whole-genome duplication (WGD / paleopolyploidy) events using wgd v2 (Chen et al 2024), KsRates (Sensalari 2022 substitution-rate-corrected Ks dating), DupGen_finder (Qiao 2019), MAPS (Li 2018 phylogenomic), POInT (Conant 2008 ordered-block), SLEDGe (2024 ML-based), Whale.jl (Bayesian DL+WGD), and synteny-anchored paranome construction. Use when identifying ancient polyploidy from Ks distributions and synteny block analysis, positioning WGD events relative to speciation, distinguishing tandem from segmental from WGD duplications, dating the 2R/3R vertebrate / fish / salmonid WGDs, building paranome and Ks-age mixture models, applying KsRates substitution-rate correction across lineages, or testing alternative biased-fractionation / dosage-balance models post-WGD.

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