「designing」の検索結果

Designs covalent inhibitors and warheads targeting cysteine (most common, 98% of covalent drugs), lysine, serine, threonine, tyrosine, and aspartate residues, with explicit handling of warhead reactivity (acrylamide, chloroacetamide, vinyl sulfone, sulfonyl fluoride, fluorosulfate, aldehyde, boronate, nitrile), reversibility (kinact/Ki, t_residence), glutathione (GSH) stability, intrinsic reactivity assays, and covalent docking (DOCKovalent, GOLD, HCovDock). Use when designing covalent inhibitors for targeted covalent inhibition (TCI), KRAS G12C-style approaches, or rationalizing covalent SAR.

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End-to-end CRISPR experiment design from target selection to delivery-ready constructs. Covers guide RNA design, off-target assessment, and specialized editing strategies including knockouts, base editing, and HDR knockins. Use when designing complete CRISPR editing experiments for gene knockout, correction, or tagging.

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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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Reconstruct ancestral states at internal phylogenetic nodes for sequences (PAML codeml, IQ-TREE --ancestral, GRASP, FastML), discrete traits (corHMM hidden-rate Markov, ape::ace, phytools::make.simmap stochastic mapping, BayesTraits), and continuous traits (phytools::fastAnc, geiger Brownian/OU, RPANDA). Use when designing constructs for ancestral protein resurrection, tracing trait evolution along a tree, performing stochastic character mapping, testing models of trait evolution (BM vs OU vs EB), inferring ancestral genome content via Dollo or DTL reconciliation, or quantifying ancestral-state uncertainty for downstream comparative analyses.

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Analyzes base-editing screens for variant function. Covers library design (Sanson 2020 GRACE, Hanna 2021 BRCA1/2 SNV scanning, Cuella-Martin 2021), CBE vs ABE chemistry choice (BE3/BE4 vs ABE7.10/ABE8.20/ABE8e), editing-window math (positions 4-8 from PAM-distal end, wider for ABE8e), bystander-edit quantification and the variant-call ambiguity it creates, sgRNA-efficiency filtering before hit calling, indel byproduct interpretation, the substitution-vs-indel diagnostic, variant annotation against ClinVar / COSMIC, and the Broad be-validation-pipeline. Use when designing a BE variant screen, choosing CBE vs ABE for a specific edit, interpreting bystander-confounded hits, distinguishing functional signal from indel artifact, integrating CRISPResso2 output with screen scoring, or deciding BE vs PE for SNV installation.

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Design guides for cytosine and adenine base editing using editing window optimization and BE-Hive outcome prediction. Select optimal positions for C-to-T or A-to-G conversions without double-strand breaks. Use when designing base editor experiments for precise nucleotide changes.

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Designs experiments to minimize and account for batch effects using balanced layouts and blocking strategies. Use when planning multi-batch experiments, assigning samples to sequencing lanes, or designing studies where technical variation could confound biological signals.

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Download large datasets from NCBI efficiently using EPost, history server, batching, rate limiting, and retry logic. Use when bulk-fetching tens of thousands of sequences, pulling all results of a large ESearch, designing reproducible pipelines, comparing E-utilities to NCBI Datasets v2 CLI, or implementing checksum-validated downloads. Encodes WebEnv TTL (~8h), EPost 200-ID limit, retmax caps, parallelization design, and integrity verification.

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Designs Bayesian clinical trials including Phase I dose-finding (BOIN, CRM, EWOC, mTPI-2), meta-analytic-predictive (MAP) priors with robust mixtures for external data borrowing, EXNEX for basket trials, hierarchical models for safety AE (Berry-Berry), Bayesian platform trials (I-SPY 2, GBM AGILE, REMAP-CAP), and posterior probability stopping rules. Covers FDA Bayesian Devices Guidance (2010), FDA Bayesian Methodology in Drugs Draft (January 2026), BOIN Fit-for-Purpose qualification (December 2021), and Project Optimus dose-optimisation. Use when designing dose-finding studies, platform trials, or sensitivity analyses with informative priors.

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End-to-end binder design using BindCraft hallucination. Use this skill when: (1) Designing protein binders with built-in AF2 validation, (2) Running production-quality binder campaigns, (3) Using different design protocols (fast, default, slow), (4) Need joint backbone and sequence optimization, (5) Want high experimental success rate. For backbone-only generation, use rfdiffusion. For QC thresholds, use protein-qc. For tool selection guidance, use binder-design.

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Solubility-optimized protein sequence design using SolubleMPNN. Use this skill when: (1) Designing for E. coli expression, (2) Optimizing solubility of designed proteins, (3) Reducing aggregation propensity, (4) Need high-yield expression, (5) Avoiding inclusion body formation. For standard design, use proteinmpnn. For ligand-aware design, use ligandmpnn.

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All-atom protein design using BoltzGen diffusion model. Use this skill when: (1) Need side-chain aware design from the start, (2) Designing around small molecules or ligands, (3) Want all-atom diffusion (not just backbone), (4) Require precise binding geometries, (5) Using YAML-based configuration. For backbone-only generation, use rfdiffusion. For sequence-only design, use proteinmpnn. For structure validation, use boltz.

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Generate protein backbones using RFdiffusion, a diffusion-based generative model for de novo protein structure generation. Use this skill when: (1) Designing binder scaffolds for a target protein, (2) Generating novel protein backbones from scratch, (3) Scaffolding functional motifs into new proteins, (4) Specifying hotspot residues for interface design, (5) Creating symmetric oligomers. For sequence design after backbone generation, use proteinmpnn. For structure validation, use alphafold or chai. For QC thresholds, use protein-qc.

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Ligand-aware protein sequence design using LigandMPNN. Use this skill when: (1) Designing sequences around small molecules, (2) Enzyme active site design, (3) Ligand binding pocket optimization, (4) Metal coordination site design, (5) Cofactor binding proteins. For standard protein design, use proteinmpnn. For solubility optimization, use solublempnn.

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Use when designing, refactoring, or debugging Formax system prompt assembly, system-reminder injection, or skills/deferred-tool prompt exposure semantics; mandatory for any change involving FORMAX_DEFERRED_TOOL_EXPOSURE and request-payload parity checks.

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Use when the user needs a professional marketer's operating mindset for any marketing, growth, or client-acquisition task — finding first customers, writing an ad or landing page, designing ad creatives and visuals (how the eye works: background, scene, hero, movement), evaluating an idea, deciding whether to do X to get Y, positioning or launching a B2B or SaaS product, running cold outreach, setting up ads, or writing copy — not a tactical template.

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Shared vocabulary for designing deep modules. Use when the user wants to design or improve a module's interface, find deepening opportunities, decide where a seam goes, make code more testable or AI-navigable, or when another skill needs the deep-module vocabulary.

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Scheduled probes that run CONTINUOUSLY after release. Covers probe design for critical user journeys, alerting integration, SLA validation, multi-region monitoring, and the boundary between QA and SRE. Use when: "synthetic monitoring," "uptime testing," "scheduled probes," "SLA validation," "availability monitoring," "post-deploy checks." Not for: safe-release techniques during rollout — use testing-in-production. Not for: designing tests from prod telemetry — use observability-driven-testing. Not for: a one-shot post-deploy smoke gate tied to a release — use release-readiness. Related: testing-in-production, release-readiness, performance-testing, qa-metrics.

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Safe-release techniques DURING rollout: feature flags, progressive rollouts, canary analysis, guardrail metrics, production smoke tests, and synthetic users. Bridges QA and SRE practices. Use when: "feature flag testing," "canary deploy," "progressive rollout," "guardrail metrics," "dark launch," "safe rollout." Not for: scheduled probes that run continuously after release — use `synthetic-monitoring`. Not for: designing tests from prod telemetry — use `observability-driven-testing`. Related: release-readiness, synthetic-monitoring, observability-driven-testing, qa-metrics.

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Hybrid fingerprint + LLM pipeline for bug classification, deduplication, and ticket generation. Normalizes CI logs, creates stable fingerprints, clusters near-duplicates, then uses LLM for severity classification and ticket writing. Includes bug reporting templates and severity/priority matrix. Use when: "bug triage," "classify bugs," "failure analysis," "auto-classify," "CI failures," "bug report," "defect template." Not for: runtime self-healing of one flaky locator — use test-reliability. Not for: designing new tests from production telemetry — use observability-driven-testing. Related: qa-metrics, qa-dashboard, ci-cd-integration, qa-project-context.

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Validate system resilience through controlled fault injection. Covers hypothesis-driven chaos experiments, failure injection types (network, service, infrastructure, dependency), LitmusChaos/Chaos Mesh/AWS FIS/Gremlin/toxiproxy tooling, automated abort gating, game day planning, and progressive chaos adoption. Use when: "chaos engineering," "fault injection," "resilience test," "game day," "failure recovery," "system reliability," "blast radius." Not for: safe rollout flags/canary/dark launch during a release — use testing-in-production; designing new tests from production telemetry — use observability-driven-testing. Related: testing-in-production, observability-driven-testing, performance-testing, release-readiness, test-environments.

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Test application performance with k6 load/stress/soak/spike scripts and k6 scenarios, Lighthouse CI for Web Vitals, and performance budgets as CI gates. Covers load profiles, custom metrics, bottleneck identification, and Core Web Vitals (LCP, INP, CLS). Use when: "performance test," "load test," "stress test," "soak test," "spike test," "k6," "k6 scenarios," "Lighthouse," "Web Vitals," "Core Web Vitals," "performance budget." Not for: scheduled production probes — use synthetic-monitoring; pixel-diff regressions — use visual-testing; designing tests from prod telemetry — use observability-driven-testing. Related: ci-cd-integration, qa-metrics, release-readiness.

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Validate release readiness with evidence-based go/no-go decisions. Covers go/no-go checklists, smoke test suite design, staged rollout validation, rollback criteria and procedures, and post-deployment verification. Ensures release confidence comes from data, not feelings. Use when: "release ready," "go/no-go," "smoke test," "release checklist," "rollback plan," "staged rollout," "canary deploy." Not for: safe-release techniques (flags, canary, dark launch) applied during the rollout itself — use testing-in-production; scheduled probes that run continuously after release — use synthetic-monitoring; designing new tests from prod telemetry — use observability-driven-testing. Related: testing-in-production, qa-metrics, ci-cd-integration, ai-system-testing.

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Apply when designing commands, lifecycle steps, or processing loops that run amid crashes, restarts, and retries. Converge to the same end state regardless of partial prior runs.

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