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Extracts, filters, annotates, and exports differential expression results from DESeq2 or edgeR with proper handling of padj=NA (independent filtering, Cook's outliers, all-zero), multiple-testing correction choice (BH vs Storey q-value vs IHW vs lfsr), TREAT vs post-hoc fold-change filtering, p-value histogram diagnostics, gene annotation via org.db/biomaRt/mygene, GSEA preranked input, ORA background construction, replication reality (Schurch 2016 small-n result), and SABV/sex-stratified reporting. Use when extracting and interpreting DE results, troubleshooting padj=NA, choosing FDR method, preparing ranked lists for pathway analysis, annotating gene IDs, or comparing DESeq2 vs edgeR outputs.

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Handles batch effects in bulk RNA-seq via design-matrix inclusion (the correct path for DE), ComBat/ComBat-seq for visualization, SVA for unknown latent factors, RUVSeq for negative-control-gene-anchored unwanted variation, and limma::removeBatchEffect for plotting only. Encodes the Nygaard 2016 cardinal sin against testing on a batch-corrected matrix, the choice between SVA/RUVg/RUVs/RUVr, the confounding non-identifiability problem, the single-cell boundary (Harmony/MNN are NOT for bulk), and the Goh 2017 harmonization critique. Use when designing a DE analysis with batch structure, troubleshooting batch-dominated PCA, choosing ComBat vs ComBat-seq, handling unknown batch via SVA, integrating across studies, or deciding when (rarely) to subtract batch.

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Estimates time-scaled phylogenies, molecular clock rates, effective reproduction number R_e (or R_t), and population dynamics from dated pathogen genomes using TreeTime (maximum-likelihood) and BEAST2 (Bayesian; strict / uncorrelated lognormal / ORC clocks; constant / exponential / Bayesian Skyline / Skygrid / BICEPS / Birth-Death-Skyline / sampled-ancestor BDSKY priors; structured coalescent via MASCOT). Covers root-to-tip clock signal QC via TempEst, date-randomisation tests (Ramsden 2009; Duchêne 2015), recombination masking via Gubbins and ClonalFrameML before clock inference for recombining bacteria, BDSKY origin-vs-rootHeight pitfalls, sampling-bias correction (Volz & Frost 2014; preferential-sampling extensions), MASCOT structured coalescent for migration, BICEPS-vs-BSP skyline choice, multi-chain BEAST2 convergence diagnostics, and reconciliation between phylodynamic R_e and case-based R_t. Use when dating outbreak origins, estimating substitution rates, inferring R_e through time, building time-calibrated Nextstrain Augur trees, choosing between strict and relaxed clocks, fitting Birth-Death-Skyline (Stadler 2013) models, diagnosing temporal-signal failure, masking recombination before clock inference for *Streptococcus pneumoniae* / *Neisseria gonorrhoeae* / *Klebsiella* / *E. coli* phylodynamics, running MASCOT for structured-population analyses, or using UShER for pandemic-scale placement.

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Analyzes single-cell pooled CRISPR screens (Perturb-seq, CROP-seq, Perturb-CITE-seq, ECCITE-seq, multiome) where each cell carries an sgRNA and a scRNA-seq / surface-protein / chromatin readout. Covers experimental design (direct-capture Perturb-seq Dixit 2016 vs CROP-seq 3'UTR-barcoded Datlinger 2017 vs ECCITE-seq vs Multiome), MOI for sgRNA assignment, escaper-cell filtering (Mixscape, Papalexi 2021), SCEPTRE NB GLM + permutation for low-MOI (Barry 2024 Genome Biol 25:124), the Pertpy framework, factor decomposition, genome-scale Perturb-seq (Replogle 2022 Cell, 2.5M cells), and per-perturbation single-cell DE. Use when running a single-cell CRISPR screen, choosing direct-capture vs CROP-seq architecture, filtering escaper cells, performing single-cell DE, integrating Perturb-seq with pathway analysis, scaling to GW CRISPRi via Replogle protocol, or analyzing multi-omics screens.

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Visualize biological networks (PPI, gene-regulatory, co-expression, pathway) with layout algorithm choice (ForceAtlas2, Fruchterman-Reingold, Kamada-Kawai, hive plots), edge bundling, community-based coloring, and reproducible seeds using NetworkX, PyVis, igraph, and Cytoscape automation. Use when rendering biological networks for static publication, interactive HTML exploration, or Cytoscape-format export.

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Compose multi-panel publication figures with patchwork, cowplot, gridExtra (R), or matplotlib GridSpec/subfigures (Python) including shared axes/legends/guides collection, panel labels in Nature/Cell convention, and journal-spec sizing. Covers patchwork ≥1.2.0 axes='collect' feature, Type-42 font embedding, and the cairo_pdf save path. Use when composing 2+ subpanels into a single figure for journal submission.

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Designs and analyzes combinatorial CRISPR screens covering paired-Cas9 (Big Papi, Najm 2018), enhanced AsCas12a multiplex (enCas12a, DeWeirdt 2021), in4mer 4-guide-array Cas12a (Esmaeili Anvar N et al 2024 Nat Commun 15:3577) and the Inzolia paralog-pair library, paralog-buffering detection (Dede 2020 Genome Biol; Thompson 2021 Cell Reports 36:109597), genetic-interaction (GI) scoring as observed_double_LFC minus expected_additive_double_LFC, synthetic-lethal and synthetic-rescue interaction interpretation, the half-of-essentiality buffered by paralogs phenomenon, multiplex screen statistical analysis with MAGeCK MLE interaction terms, and the relationship to single-cell combinatorial Perturb-seq. Use when designing a paralog or pathway-pair screen, choosing between paired-Cas9 (Big Papi) and Cas12a multiplex (Inzolia), interpreting genetic interaction scores, identifying synthetic-lethal targets for drug development, or scaling beyond single-gene CRISPR screens.

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Queries ClinVar for variant pathogenicity classifications, ClinGen VCEP curations, and somatic-vs-germline interpretations via REST API, weekly VCF, or bulk XML. Use when determining clinical significance, triangulating conflicting interpretations, or aggregating evidence against the ACMG/AMP framework with ClinGen SVI specifications.

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Detect horizontal gene transfer (HGT / LGT) using compositional methods (GC%, codon usage, tetranucleotide z-scores via SIGI-HMM, AlienHunter, IslandViewer 4, IslandPath-DIMOB), phylogenetic-incongruence methods (AvP, HGTphyloDetect, ALE / GeneRax / AleRax reconciliation, RANGER-DTL), and BLAST-distribution methods (HGTector v2, DarkHorse, Alien Index). Use when screening prokaryote genomes for genomic islands and HGT events, distinguishing HGT from incomplete lineage sorting / differential gene loss / hybridization, mapping donor lineages via phylogenetic placement, separating eukaryotic HGT from contamination, ruling out gBGC as a false signal, or quantifying DTL rates with ALE/GeneRax on bacterial trees.

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Applies ACMG/AMP 2015 framework with ClinGen SVI specifications, Tavtigian 2018/2020 Bayesian point system, Abou Tayoun 2018 PVS1 decision tree, Pejaver 2022 calibrated PP3/BP4 thresholds for REVEL/BayesDel/AlphaMissense, Brnich 2020 PS3/BS3 OddsPath, Walker 2023 SpliceAI splicing framework, and AMP/ASCO/CAP 2017 tumor tiers. Use when classifying germline variants P / LP / VUS / LB / B, applying VCEP-specific CSpec rules, computing Whiffin BS1, or assigning cancer Tier I-IV per Li 2017.

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Decompose total effects into direct and indirect paths through mediators using mediation, CMAverse 4-way, HIMA/HIMA2 high-dimensional, BAMA, two-step / MVMR mediation, or double-ML medDML. Use when testing whether a molecular phenotype (expression, methylation, protein) mediates a treatment-outcome relationship, decomposing exposure-mediator interaction via VanderWeele 4-way, screening high-dimensional EWAS mediators, or running MR-based mediation when sequential ignorability is implausible.

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Predicts whether a DNA variant alters mRNA splicing using sequence-based deep-learning tools — SpliceAI (10kb context dilated CNN, clinical default), Pangolin (multi-tissue), MMSplice (modular per-region CNN with calibrated ΔPSI), SpliceTransformer/TrASPr (tissue-aware transformers), SpliceVault (empirical 300K-RNA lookup of likely mis-splicing outcomes), CADD-Splice (composite score). Applies the ClinGen SVI 2023 framework for ACMG/AMP variant interpretation (PVS1, PP3, BP4 evidence codes), HGVS splicing nomenclature (c.123+1G>A, c.123-3T>G, r.spl?), extended-window scoring for deep-intronic pseudoexons, tissue-specific predictions, branchpoint variant detection (BPHunter, LaBranchoR), and splice-switching ASO design. Use when interpreting splice impact of clinical variants, prioritizing VUS, identifying deep-intronic pathogenic variants, or designing ASOs.

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Use this skill when the user asks about the financial differences between being an owner-operator vs company driver — gross pay, expenses, net pay, capital requirements, risk tolerance, lifestyle, and how to evaluate the path. Reference industry pay surveys.

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Use when a driver has been disqualified or is at risk of disqualification — major offense convictions (DUI, leaving the scene, drug trafficking with CMV), serious traffic violations, RR-grade-crossing violations, imminent-hazard out-of-service, or Clearinghouse positive-test prohibited status. Also use when planning a return-to-duty pathway, SAP process, or reinstatement timeline. Covers 49 CFR 383.51, Part 40 Subpart O, and Part 391.15.

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Use when a carrier needs to build an internal dispatcher training program, onboard new dispatchers, or certify dispatcher competency. Covers job description, required skills, training modules, certification frameworks (CDS, CTP), shadowing, evaluation, and career path.

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Use when discussing the mobile apps drivers use day-to-day — load boards (DAT, Truckstop), route planners (Trucker Path, CoPilot Truck), expense and per diem apps (Per Diem Plus), parking apps (Park My Truck), maintenance / DVIR apps, and how these stack with the carrier's ELD app.

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Decision-ready scouting record for a user-connected provider access campaign. Use when an assigned Provider Access Launch task needs its easiest official route, minimum scopes, cost, account needs, approval path, implementation consumer, and easy-execute verdict established before submission. NOT for client Local Listings distribution.

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The gate and path for any question an agent wants Arman to decide. Use when about to ask him anything, ending a turn on a question for him, writing 'needs Arman's decision', marking work blocked on him, or on /ask-arman. NOT for a step only he can perform (use a guided session).

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Locate CEconItemView::operator= in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the WeaponPaints gamedata entry "CEconItemView::operator=" (symbol CEconItemView_operator=). Copy-assignment operator. Shortlist via call sites in weapon-give/refresh paths that copy an existing CEconItemView into another (this-pointer copy of definition index, seed, wear, attribute list and item ID fields — a field-by-field copy, not a memcpy). Trigger: CEconItemView_operator=, CEconItemView::operator=

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Locate CCSPlayerInventory::SendInventoryUpdateEvent in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the WeaponPaints gamedata entry "CCSPlayerInventory::SendInventoryUpdateEvent" (symbol CCSPlayerInventory_SendInventoryUpdateEvent). Shortlist via functions constructing the inventory-full-update usermessage/event around m_pSOCache contents for the owning controller. The body packs the SO cache snapshot and sends it via the GC/usermessage path. Cross-check with callers in inventory-dirty flows (weapon paint mutations). Trigger: CCSPlayerInventory_SendInventoryUpdateEvent, CCSPlayerInventory::SendInventoryUpdateEvent

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Locate CCSPlayerPawn::SetModelFromLoadout in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the WeaponPaints gamedata entry "CCSPlayerPawn::SetModelFromLoadout" (symbol CCSPlayerPawn_SetModelFromLoadout). Shortlist alongside SetModelFromClass (same file/call region — sibling paths in pawn model selection). This variant resolves the model from the player's loadout/inventory items (agent skin selection), referencing inventory services and item definition indexes before calling SetModel. Trigger: CCSPlayerPawn_SetModelFromLoadout, CCSPlayerPawn::SetModelFromLoadout

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Locate CCSPlayerInventory::GetItemInLoadout in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the WeaponPaints gamedata entry "CCSPlayerInventory::GetItemInLoadout" (symbol CCSPlayerInventory_GetItemInLoadout). Non-virtual inventory method resolving a player's loadout item. Shortlist via callers inside CCSPlayerInventory code that walk the loadout item cache (m_pSOCache / CGCClientSharedObjectCache), and via the CSO/econ loadout message paths. The function takes an item definition index + loadout slot and returns the matching CEconItemView — the body iterates a small item list comparing definition indices and loadout slots. Trigger: CCSPlayerInventory_GetItemInLoadout, CCSPlayerInventory::GetItemInLoadout

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Build a LiveAvatar integration end-to-end — assesses the user's existing stack, recommends the optimal path, and guides implementation. Use when: (1) Building a new LiveAvatar integration, (2) Adding a real-time avatar to an app or site, (3) Connecting LiveAvatar to an existing AI pipeline, (4) User mentions LiveAvatar, real-time avatar, interactive avatar, conversational avatar, or lip-sync avatar, (5) Deciding between Embed, FULL Mode, and LITE Mode, (6) Migrating from HeyGen Interactive Avatar to LiveAvatar.

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Build voice AI agents with LiveKit Cloud and the Agents SDK. Use when the user asks to "build a voice agent", "create a LiveKit agent", "add voice AI", "implement handoffs", "structure agent workflows", or is working with LiveKit Agents SDK. Provides opinionated guidance for the recommended path: LiveKit Cloud + LiveKit Inference. REQUIRES writing tests for all implementations.

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