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Imports gene expression count matrices from featureCounts, HTSeq, STAR ReadsPerGene, Salmon/kallisto via tximport or tximeta, RSEM, 10X Genomics MTX/H5, AnnData H5AD, and RDS. Handles silent-miscounting traps (featureCounts -p v2.0.2 API break, STAR strandedness column choice, salmon NumReads-sum without tximport, RSEM non-integer expected_count, GENCODE _PAR_Y suffix, zero-length-transcript TPM divide-by-zero), and encodes the tximport countsFromAbundance decision tree with the "lengthScaledTPM is not TPM" warning. Use when assembling a gene-by-sample count matrix from aligner or quantifier output, importing salmon/kallisto for DESeq2 vs limma-voom, choosing strandedness column for STAR, debugging zero-count panics, or building tx2gene mapping.

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Compare gene co-expression and regulatory networks between biological conditions to find rewired relationships using DiffCorr, DiffCoEx, DINGO/iDINGO, and CoDiNA. Covers the differential-connectivity-is-not-differential-expression distinction, the pairwise multiple-testing explosion, marginal vs partial (direct) rewiring, and the underpowered-rewiring failure mode. Use when comparing co-expression networks between disease vs control, treatment, or developmental stages, or finding hub genes that rewire without changing mean expression. For single-condition modules see coexpression-networks; for differential expression of means see differential-expression/de-results.

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Unsupervised clustering and cell-type identification for high-dimensional flow, spectral, and mass cytometry - FlowSOM, PhenoGraph, FlowSOM-via-CATALYST, with UMAP/tSNE for visualization. Covers the type-vs-state marker distinction (cluster on lineage, test state within clusters), over-provision-then-metacluster, the Weber-Robinson benchmark, seed dependence and metacluster stability, why embeddings are for looking not measuring, and median-heatmap annotation/merging. Use when discovering populations without predefined gates, choosing a clustering algorithm, selecting the number of metaclusters, or annotating clusters into cell types.

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Detects m6A modifications from Oxford Nanopore direct-RNA-seq (DRS) signal using m6Anet (multiple-instance-learning over DRACH 5-mer signal). Covers the upstream pipeline (Dorado/Guppy basecalling -> minimap2 map-ont -> nanopolish eventalign -> m6anet dataprep -> m6anet inference), per-site vs per-read probability including the mod_ratio stoichiometry column, the DRACH-only constraint, minimum-coverage thresholds (20-50 reads/site), multi-condition comparison via xPore/Nanocompore/ELIGOS, Dorado native modification calling (RNA004, 2024+), and the cDNA-vs-DRS distinction (cDNA Nanopore CANNOT detect modifications). Use when calling m6A from ONT DRS without immunoprecipitation, choosing m6Anet vs xPore vs Nanocompore vs ELIGOS vs Dorado native, interpreting probability_modified vs mod_ratio vs per-read probabilities, deciding between m6Anet (known DRACH sites) and Dorado/Remora (genome-wide screening), pinning RNA002 vs RNA004 chemistry and basecaller versions, or troubleshooting eventalign/dataprep failures.

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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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Predict RBP binding from RNA sequence using deep learning models (RBPNet sequence-to-signal, RNAProt RNN, GraphProt2 GCN with structure, DeepCLIP, DeepRiPe multi-modal CNN) for variant-effect prediction, in silico binding-site discovery, model interpretation, and transfer learning from CLIP and RBNS datasets. Use when computational prediction of RBP binding from sequence is needed, evaluating variant effects on binding without further wet-lab experiments, comparing model performance, or training a custom model on ENCODE eCLIP data.

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Queries myvariant.info BioThings aggregator for ClinVar, gnomAD, dbSNP, dbNSFP, COSMIC, CADD, and CIViC annotations in batched, version-tracked requests. Use when annotating variant lists from multiple databases simultaneously without managing per-source APIs, and when reproducibility-grade analyses require recording source data versions via _meta.

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Process many sequence files in batch (count, merge, split, convert, summarize) with memory-safe streaming and on-disk indexing using Biopython, pysam, or pyfastx. Use when iterating over a directory of FASTA/FASTQ files, merging or splitting datasets, building random access across many or huge files, or automating per-file operations without exhausting RAM.

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Infer cis-regulatory connections (peak-to-peak co-accessibility) from scATAC-seq using Cicero, ArchR getCoAccessibility, or SCENIC+. Use when linking enhancer accessibility to promoter accessibility, identifying enhancer-gene pairs from chromatin alone (without paired RNA), running gene-regulatory inference combining ATAC + RNA, or comparing predicted regulatory contacts against Hi-C/Micro-C ground truth.

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Autonomously improve a real artifact (code, training recipe, agent harness, data pipeline, prompt) against an objective and an evaluator, using Hypothesis Tree Refinement (HTR) from the Arbor paper. Use this whenever someone wants to iteratively optimize something over many experiments without overfitting — e.g. "get my model's eval score up", "improve this agent/harness", "tune this pipeline", "beat the baseline on this benchmark", "run a search over approaches and keep the best", "do an MLE-bench / Kaggle-style optimization", or any long-horizon "make this artifact better and don't just memorize the dev set" task. Trigger it even when the user doesn't say "Arbor" or "hypothesis tree" but describes repeated experiment-and-evaluate loops, branching exploration of competing ideas, or worries about a dev/test gap. Runs Claude itself as the coordinator with subagent executors in isolated git worktrees; for the standalone `arbor` CLI tool see references/arbor-upstream.md.

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This skill suggests continuing personal CGM with or without ADIP rather than discontinuation for inpatients already using it who are at high risk for hypoglycemia. Trigger phrases include "Should I continue or discontinue personal CGM for this inpatient who is already using it?" and "Is it appropriate to maintain personal CGM during hospitalization?"

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Recommends continuing a patient’s personal continuous glucose monitor (CGM) in the hospital with or without algorithm-driven insulin pump (ADIP) therapy rather than discontinuing it for individuals already using CGM outpatient. Use when deciding whether to maintain personal CGM during admission or when a patient requests to keep their device, particularly in those at high risk for hypoglycemia.

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Recommends use of hybrid closed-loop pump rather than insulin pump with CGM (without algorithm) or multiple daily injections with CGM for pregnant individuals with type 1 diabetes. Triggered when deciding on insulin delivery methods for pregnant patients with type 1 diabetes.

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This skill recommends against initiating cortisol-lowering treatment when there is no established diagnosis of Cushing's syndrome. It is triggered when a clinician considers treating suspected CS based only on borderline biochemical abnormalities or nonspecific signs without confirmatory testing; examples include "suspected CS", "borderline UFC", "no confirmed diagnosis", "consider empiric ketoconazole".

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Identifies patients with normokalemia and no adrenal tumors on CT who likely have bilateral PA and may proceed directly to medical therapy without AVS. Triggers include when a clinician notes normokalemia and clean adrenal CT and asks 'Is AVS necessary if I suspect bilateral disease?'

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Determines successful catheterization in adrenal venous sampling by applying selectivity index cut‑offs with and without ACTH stimulation. Triggered during AVS when measuring cortisol levels and asking “Is the catheter properly positioned?” or when reviewing results for technical adequacy.

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Identifies patients with a positive aldosterone-to-renin ratio screening who may proceed directly to subtype testing without confirmatory testing based on specific clinical criteria. Triggers include spontaneous hypokalemia, baseline plasma aldosterone concentration >100 pg/mL (CLEIA), renin suppression, or a clinician questioning the need for a confirmatory test after a positive screen.

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Identifies young patients with classic primary aldosteronism features who may proceed directly to unilateral adrenalectomy without adrenal venous sampling based on high probability of unilateral disease. Triggered when a clinician sees a patient <35 years with hypokalemia, unilateral adrenal tumor on CT, and high plasma aldosterone concentration and asks whether AVS can be bypassed.

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Recommends confirmatory testing with corticotropin stimulation test in patients presenting with clinical symptoms or signs suggesting PAI (e.g., fatigue, hypotension, hyponatremia, hyperpigmentation) when the patient's condition permits safe testing. Use when a clinician identifies suggestive features and circumstances allow outpatient stimulation testing without imminent need for emergency glucocorticoids.

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Reconcile baseline-versioned files that the `create-baseline upgrade` CLI staged for LLM-assisted semantic merge. Use when the CLI prints "Open Claude Code and run /upgrade-project to reconcile". Reads the stage manifest at `.claude/state/upgrade/<ts>/manifest.json`, reasons through each pending file's three-way delta in main context, writes a reconciled LOCAL, then deletes the stage when every file lands. Supports `--dry-run` (preview the reconciled diff without writing) and a structured "needs-user-input" fallback when the conflict cannot be disambiguated automatically.

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Capture what someone actually said without contaminating it with your own inference. Invoke when eliciting intent in conversation (design discussion, requirement interview, decision surfacing) and when turning a conversation into a durable record (ADR, decision node, memory entry, spec `## Decisions` row). Enforces quote-before-critique, keeps illustration separate from commitment, and holds interpretation subordinate to verbatim. Prevents the failure where unspecified space is filled by the recorder and then evaluated as if the speaker had specified it.

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Bring documentation prose down to a high-school reading level without losing precision. Runs after the content is written and before humanizer. Targets grade 9 on four measures — sentence length, vocabulary, clause load and jargon density — and carries the rewriting moves that actually shift them.

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Preflight a spec draft without saving. Runs the same checks as the write-boundary hooks — PlantUML syntax, required diagram presence, AC-to-sequence traceability, Design calls quality floor, and System delta row resolution — and prints a compact pass/fail table. Use while iterating so the hooks don't bite on save.

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Use when facing 2+ independent tasks that can be worked on without shared state or sequential dependencies

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