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Prioritizes rare-disease variants from trio/quad WES/WGS with de novo (DeNovoGear, Triodenovo), compound-heterozygous phasing (WhatsHap), mosaic VAF tiering, phenotype-driven ranking (Exomiser, Phen2Gene, AMELIE), ClinGen gene-disease validity gating, and ACMG SF v3.2 secondary findings reporting. Use when running diagnostic exome / genome pipelines, identifying candidate Mendelian disease genes, screening for incidental findings, or auditing VUS reclassification cycles. The ACMG/AMP classification framework (PVS1 decision tree, Pejaver PP3/BP4 calibration, Tavtigian point system) is in clinical-databases/acmg-classification.

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Runs cis-pQTL Mendelian randomization for drug-target validation using UKB-PPP (Olink), deCODE (SomaScan), Fenland, INTERVAL, ARIC, and FinnGen-PPP proteomes plus colocalization triangulation, phenome-wide on-target adverse-effect scans, cross-platform Olink/SomaScan replication, and PAV (protein-altering variant) sensitivity. Use when nominating or de-risking a drug target from plasma-proteome GWAS, mimicking pharmacological inhibition via cis-pQTL instruments, separating shared-causal from LD-confounded signal under the Schmidt 2020 cis-MR framework, screening on-target adverse phenotypes pheWAS-style, or producing publication-grade STROBE-MR plus PP.H4 evidence for a target gene.

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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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Queries PharmGKB / CPIC / DPWG for drug-gene interactions; calls CYP2D6/CYP2C9/CYP2C19/DPYD/TPMT/NUDT15/UGT1A1/SLCO1B1 star alleles and phenotype with PharmCAT, Cyrius (CYP2D6 structural variants), Aldy, Stargazer; applies Caudle 2020 activity-score translation. Use when implementing pharmacogenomic-guided prescribing, applying CPIC vs DPWG guidance, screening HLA risk alleles for ICI / antiepileptics / abacavir, or interpreting compound TPMT+NUDT15 thiopurine risk.

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Calls microsatellite instability from WES/WGS/targeted-panel with MSIsensor, MSIsensor-pro, MSIsensor-ct (panel-aware), mSINGS, and MANTIS for FDA pembrolizumab MSI-H pan-tumor / Lynch syndrome / dMMR ICI biomarker. Use when stratifying ICI eligibility (Le 2015), pairing MSI with TMB-H (Sha 2020 / Salem 2018), screening Lynch syndrome (universal IHC + MSI), or distinguishing MSI-H tumors from POLE-exo hypermutator with overlapping signatures.

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Calls HLA class I and class II alleles at 2/4/6/8-field resolution from WGS/WES/RNA-seq/long-read data using OptiType, HLA-LA, T1K, Polysolver, HLA-HD, arcasHLA, StarPhase, or HIBAG imputation. Use when typing for HSCT, solid-organ transplant, neoantigen prediction, PGx screening (B*57:01, B*15:02, etc.), or disease-association studies, with reconciliation across tools and IPD-IMGT/HLA version mismatch handling.

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Estimates bivariate genetic correlation (rg) between traits from GWAS summary statistics or individual-level genotypes using cross-trait LDSC, HDL, LAVA, rho-HESS, GREML-bivariate, Popcorn, and HDL-L. Use when quantifying shared genetic architecture between two traits, screening MR validity before causal inference, distinguishing global from locus-level rg, estimating trans-ancestry rg, separating partial from full causation via LCV gcp, or producing a STROBE-MR-compliant cross-trait sensitivity battery. Cross-trait LDSC intercept absorbs sample overlap and is NOT a bias; HDL is biased under sample overlap above ~5%. High rg between exposure and outcome motivates CHP-aware MR sensitivity (CAUSE, LHC-MR).

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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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Walks a cardiologist through whether, where and how to order a germline genetic test for a suspected inherited cardiovascular disease: indication, written consent (with assent for minors), pre-test counseling, choice of test and laboratory, handling of VUS and secondary findings, and privacy. Use when a clinician asks 'should I order a genetic test', 'how do I consent for a cardiomyopathy or long QT gene panel', 'can I test this child or relative (cascade screening)', 'what do I tell the patient about VUS or a negative result', or 'where can this test be sent'. Based on the JCS/JCC/JSPCCS 2024 guideline; Japan-specific insurance and legal details are flagged.

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Evaluates cardiovascular risk factors in persons receiving hormone therapy by obtaining fasting lipid profiles and diabetes screening. Triggered when a patient is on gender-affirming hormone therapy and due for routine cardiovascular risk assessment.

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Provides monitoring schedule for transgender females on estrogen therapy, including clinical evaluation, hormone levels, prolactin, electrolytes, BMD, and cancer screening. Triggered when a transgender female is receiving estrogen therapy for gender affirmation.

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This skill screens for pregnancy intention in individuals with preexisting diabetes at every reproductive, diabetes, primary care, and urgent care/ER visit when clinically appropriate. Trigger phrases include reproductive planning, preconception care, or pregnancy intention discussion.

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This skill recommends using biochemical tests to screen for hypercortisolism to detect recurrence in patients with ACTH-dependent Cushing's syndrome after surgical remission. It is triggered during postoperative follow-up when the HPA axis has recovered, annually, or sooner if clinical signs of hypercortisolism (e.g., weight gain, hypertension, glucose intolerance) or abnormal late-night salivary cortisol/UFC appear.

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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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Determines whether a hypertensive patient should be screened for primary aldosteronism based on clinical features associated with higher PA prevalence. Triggered when a clinician asks 'Should I screen this hypertensive patient for PA?' or observes spontaneous hypokalemia, resistant hypertension, hypertension onset before age 40, adrenal tumor, young-onset stroke, or sleep apnea syndrome.

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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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Recommends correcting serum potassium to the laboratory reference range and repeating aldosterone-to-renin ratio (ARR) screening when the initial screen is negative in a hypertensive patient with hypokalemia. Use when a clinician encounters a negative PA screen in a hypertensive patient with hypokalemia and wonders whether to repeat testing after potassium repletion.

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Recommends withdrawing interfering medications and repeating aldosterone-to-renin ratio screening when initial screen is negative but clinical suspicion remains due to hypokalemia or medication interference. Trigger phrases include "initial screen negative", "hypokalemia", "resistant hypertension", and use of MRAs, ACE inhibitors, ARBs, beta-blockers, clonidine, or alpha-methyldopa.

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Complete bedside prescribing reference for Mirago (mirabegron, beta-3 adrenoceptor agonist) for overactive bladder — covering contraindications, safety screening, drug interactions, dose selection in special populations, titration, and administration. Use when a clinician asks how to start mirabegron, what dose to use in renal or hepatic impairment, is mirabegron safe in this patient, mirabegron drug interactions, or Mirago for OAB.

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Discover prospect companies from a structured OpenClaw search brief, including public search and user-authorized data sources, then output a conservative candidate list ready for lead screening.

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Run or resume a deliverable active-outreach workflow across lead discovery, screening, customer intel, and outreach email. Use when an operator or system pipeline needs durable run state, visible intermediate artifacts, evidence gates, report-bound human approval, and a final editable email draft that is never auto-sent.

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Normalize and screen scattered foreign-trade leads into a conservative, structured lead pool that can flow into customer-intel research. Use when an operator has company names, websites, emails, or contact clues from search results and needs a standardized output with missing-field warnings, review flags, next-step suggestions, and customer-intel-ready JSON.

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Find the first batch of foreign-trade prospect companies from public web, LinkedIn, and user-authorized data sources such as customs exports, trade show lists, association directories, CRM/Excel files, or historical customer data, then output a conservative, structured candidate list ready for lead screening.

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Bilingual JD/CV/Resume tailoring and resume polish skill for job applications. Use when the user provides a job description, JD, role posting, existing CV/resume, LinkedIn profile, portfolio, or career notes and wants to optimize, rewrite, polish, or customize a resume/CV for ATS keywords, recruiter screening, interview-ready evidence, and role fit. 适用于根据招聘 JD、岗位描述、目标公司、现有简历/CV/LinkedIn/profile 进行简历优化、简历润色、岗位匹配、ATS 关键词映射、经历深挖、项目证据提炼和中英文求职简历定制。

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