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Analyzes species-environment relationships with constrained ordination (CCA, RDA, db-RDA), variance partitioning, indicator species (indicspecies IndVal.g group-equalized), PERMANOVA paired MANDATORILY with PERMDISP (Anderson & Walsh 2013; dispersion confounds centroid tests), Joint Species Distribution Models (HMSC, sjSDM, gjam) with explicit rejection of "residual covariance equals biotic interaction", phylogenetic community ecology (SES_MPD/MNTD), trait-environment via RLQ + fourth-corner with corrected modeltype=6 (Dray 2014), bipartite network metrics (NODF, modularity) with curveball null (Strona 2014), and Mantel-test replacements (dbRDA, GDM) for spatial data. Use when testing how environmental gradients structure communities, identifying habitat indicator taxa, partitioning variance among predictors, deciding whether PERMANOVA significance is location vs dispersion, picking among HMSC/sjSDM/gjam, or replacing Mantel tests for landscape data.

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Resolve subclonal copy number, whole-genome doubling, and copy-number tumor evolution from bulk sequencing with Battenberg, TITAN, and MEDICC2. Covers clonal versus subclonal copy-number states, haplotype phasing for subclonal resolution, cancer cell fraction, whole-genome-doubling detection and timing relative to mutations, mirrored subclonal allelic imbalance, and copy-number phylogenies. Use when a tumor is heterogeneous and bulk data shows non-integer copy number, when calling subclonal CNAs, detecting or timing whole-genome doubling, reconstructing copy-number evolution, or deciding between Battenberg and TITAN.

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Decides how to preprocess plasma cfDNA sequencing data so the recoverable signal survives - library-prep-aware fragment expectations (dsDNA vs ssDNA/adaptase prep), UMI/duplex consensus with fgbio (ExtractUmisFromBam, GroupReadsByUmi --strategy paired for duplex, CallMolecularConsensusReads vs CallDuplexConsensusReads, FilterConsensusReads min-reads "total s1 s2"), the align->group->consensus->RE-align ordering, and the cfDNA dedup trap where naive coordinate dedup collapses nucleosome-coincident independent molecules. Covers when single-strand consensus suffices vs when duplex is mandatory, the singleton/sensitivity tax at low input, and reading the insert-size histogram as a pre-analytical QC instrument. Use when processing plasma cfDNA reads before fragmentomics, ctDNA mutation calling, or tumor-fraction estimation.

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Expert guide for Backend.AI distributed computing platform. Automatically activates when users ask about: - Backend.AI architecture, components (Manager, Agent, Storage Proxy, Webserver, App Proxy) - Features (session scheduling, Sokovan orchestrator, multi-tenancy, resource allocation) - APIs (REST, GraphQL), authentication, RBAC authorization - Container runtime (kernels, jail sandbox, hook library, virtual folders) - Accelerator support (CUDA, ROCm, TPU, NPU, Graphcore IPU) - Client SDKs (Python, Java, JavaScript, PHP) - Setup, requirements (Python 3.13+, Docker, PostgreSQL, Redis, etcd) - How WebUI connects to/interacts with Backend.AI backend - Plugin interfaces, development setup, infrastructure Use when user mentions "Backend.AI", "backend.ai", "Sokovan", component names, or asks about the backend platform this WebUI connects to. allowed-tools: WebFetch, Read

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Treats a ctDNA assay as a molecule-counting experiment at the Poisson edge and builds its analytical-validation case the measurement-science way. Covers the genome-equivalent currency (~330 haploid copies/ng), the lambda = input_GE x VAF sampling ceiling (lambda>=3 for ~95% detection), the error-suppression ladder (raw NGS ~1e-3 -> single-strand UMI ~1e-4/1e-5 -> duplex <1e-7), the CLSI EP17 LoB/LoD/LoD95/LoQ framework, the per-locus-vs-panel-integrated LoD distinction that lets bespoke MRD reach ppm, contrived/SEQC2 reference standards, and honest LoD reporting conditioned on input mass + consensus depth + replicate detection rate. Use when stating or trusting a sensitivity claim, designing a dilution-series validation, deciding how many genome equivalents are needed at a target VAF, choosing a single-locus vs panel-integrated LoD, or auditing a "detects 0.1% VAF" claim.

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How to use the Adaptyv Bio Foundry API and Python SDK for protein experiment design, submission, and results retrieval. Use this skill whenever the user mentions Adaptyv, Foundry API, protein binding assays, protein screening experiments, BLI/SPR assays, thermostability assays, or wants to submit protein sequences for experimental characterization. Also trigger when code imports `adaptyv`, `adaptyv_sdk`, or `FoundryClient`, or references `foundry-api-public.adaptyvbio.com`.

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Infers genetic super-population ancestry from a 23andMe/AncestryDNA file and computes ancestry-stratified odds ratios with an exploratory Ancestry Elevation Score (AES) showing where ancestry-specific GWAS effect sizes diverge from European reference estimates.

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Plan, execute, and document validation, verification, and transfer of analytical procedures under the governing framework - ICH Q2(R2) and Q14, USP <1220>/<1225>/<1226>, ICH M10 bioanalytical, CLSI EP, or ISO/IEC 17025. Use for HPLC, LC-MS/MS, GC, CE, ICP-MS, dissolution, qNMR, qPCR, NIR, and ligand binding or cell-based assays whenever the question is whether a procedure is fit for its intended purpose. Triggers include "method validation", "analytical method validation", "AMV", "validation protocol", "acceptance criteria", "linearity", "reportable range", "accuracy and precision", "repeatability", "intermediate precision", "recovery", "LOD", "LOQ", "detection limit", "quantitation limit", "specificity", "robustness", "method transfer", "method comparison", "Deming", "Passing-Bablok", "Bland-Altman", "equivalence testing", "OOS investigation", "ICH Q2", "Q2(R2)", "Q14", "USP 1225", "ICH M10", "incurred sample reanalysis", "ISR", "CLSI EP", and any request to show that an assay works.

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Apply the four published expert-consensus clinical scenarios to manage GI adverse events in complex GLP-1 receptor agonist patients — persistent nausea mid-titration, GERD/heartburn after up-titration, elderly with sarcopenia risk, and insulin-treated elderly with CKD plus diarrhoea. Use when a clinician describes a patient resembling one of these archetypes, or asks "how to manage GLP-1 in an elderly patient with CKD", "patient on liraglutide developed reflux", "sarcopenia worry on semaglutide in 80-year-old", or "persistent nausea on semaglutide despite escalation". Grounded in Gorgojo-Martínez 2023 Table 4.

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Assesses patient’s understanding of how CGM data (trends, rates of change) differ from discrete SMBG fingerstick values. Triggered when clinicians hear requests to explain lag and trend arrows on CGM or teach the difference between CGM glucose and fingerstick glucose.

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This skill recommends using radiation therapy for corticotroph adenomas in Cushing's disease when imaging shows invasive features or mass‑effect concerns such as cavernous sinus invasion, suprasellar extension, or knobby protrusion. Consider RT when postoperative medical therapy has normalized cortisol but tumor progression or residual invasive disease is suspected.

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This skill recommends transsphenoidal selective adenomectomy (TSS) by an experienced pituitary surgeon as the optimal treatment for Cushing's disease in pediatric and adult patients. Use when a patient with ACTH-dependent Cushing syndrome is a surgical candidate; triggers include overt Cushing's syndrome, elevated UFC or late-night salivary cortisol, and pituitary MRI showing an adenoma.

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This skill recommends measuring late-night salivary or serum cortisol to screen for Cushing's disease recurrence in patients with eucortisolism after transsphenoidal surgery, including cases where eucortisolism was established by medical treatment prior to surgery. Use when postoperative follow-up shows eucortisolism (normal morning cortisol/UFC) but concern for recurrence exists.

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This skill recommends lifelong biochemical testing for recurrence in all patients with Cushing's syndrome after adrenalectomy, except those with resected adrenal adenoma showing CT density <10 Hounsfield units. Use when determining long‑term follow‑up strategy for a post‑adrenalectomy CS patient; triggers include “post‑adrenalectomy Cushing’s syndrome”, “CT density <10 HU”, and “adrenal adenoma resection”.

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Work up a patient with confirmed hypercalcemia using the PTH-dependent vs. PTH-independent algorithm — order the right second-tier tests (PTHrP, 25(OH)D, 1,25(OH)2D, SPEP/UPEP, urinary calcium/creatinine clearance ratio, TSH) to reach a diagnosis. Trigger when a clinician asks "what's causing this hypercalcemia", "how to work up high calcium", "what tests to order for hypercalcemia", "PTH is normal what next", "differential diagnosis of hypercalcemia", or shares a confirmed hypercalcemia and asks for the workup.

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Recommends additional treatments for patients with persistent overt hypercortisolism after initial surgical intervention for Cushing's syndrome. Trigger phrases include "post-op CS patient shows ongoing hypercortisolism," "persistent overt hypercortisolism after TSS," and "elevated UFC or midnight salivary cortisol following surgery."

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Suggests repeat transsphenoidal surgery for patients with persistent hypercortisolism after initial transsphenoidal surgery when imaging shows evidence of incomplete resection or a pituitary lesion. Clinical triggers include postoperative MRI revealing residual adenoma, persistent elevated UFC or late-night salivary cortisol, and visible pituitary lesion on imaging.

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Adjusts intravenous bisphosphonate dosing and infusion duration for patients with hypercalcemia of malignancy and renal insufficiency (creatinine clearance <60 mL/min). Triggered when a clinician encounters renal impairment and asks how to modify zoledronic acid or pamidronate infusion rates.

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Recommends potassium supplementation for hypokalemia management in PA patients who are pregnant or planning pregnancy. Triggered when a pregnant PA patient presents with low serum potassium and asks 'How should I treat hypokalemia?' or when electrolytes are reviewed.

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Determines the appropriate IV pamidronate dose (60‑90 mg) and infusion duration (2‑24 h) for adults with hypercalcemia of malignancy based on renal function. Triggered when a clinician orders pamidronate and asks how to adjust for kidney dysfunction (eGFR < 60 mL/min/1.73 m²).

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Provides a checklist of five evidence-based measures to enhance the technical success of adrenal venous sampling procedures. Triggers include when preparing for AVS and asking 'How can I maximize success rate?' or troubleshooting failed attempts.

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Interprets the aldosterone-to-renin ratio using active renin concentration (ARC) to screen for primary aldosteronism. Triggered when a clinician has PAC and ARC results and asks 'How do I interpret this ARR using active renin concentration?'

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Interprets the postural stimulation test to detect angiotensin II‑unresponsive aldosterone‑producing adenoma (APA) or familial hyperaldosteronism type I (FH‑I) when aldosterone fails to rise with upright posture. Triggered by clinical cues such as “postural stimulation test shows no aldosterone increase”, “suspected APA with non‑responsive aldosterone”, or “evaluating FH‑I in young patients with early‑onset hypertension and hypokalemia”.

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Select the right pharmacologic agent for a child aged 12+ with obesity using the CMAJ 2025 guideline — choosing between GLP-1 receptor agonists, metformin, or orlistat with monitoring guidance. Trigger when a clinician asks which medication to use for pediatric obesity, whether to start semaglutide or metformin in a child, or how to manage obesity pharmacologically in adolescents.

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