「alignment」の検索結果

Capture the "why" behind technical choices to prevent architectural drift. Load when the user makes a major technical decision, chooses a library/framework, defines a system boundary, or changes a core architectural pattern. Also triggers on "record a decision", "write an ADR", "why did we do this", "document this architectural choice", or "architectural decision record". Supports `SYNTHESIS=true` mode for retrospective ADR backfill from observed repo state — used by `retroactive-project-setup` and any future backfill skill. Essential for long-term project maintainability and agent alignment.

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Turns Hi-C/Micro-C FASTQ into a deduplicated, filtered .pairs file with pairtools and decides whether the library worked. Covers the bwa mem -SP5M / bwa-mem2 / chromap --preset hic alignment idiom (mates mapped as independent single-end reads), pairtools parse vs parse2 and the walks-policy choice (5unique pairwise vs all for Pore-C/Micro-C concatemers), pair-type classification (keep UU and rescued UC), dedup (PCR vs optical/by-tile), select by pair_type/MAPQ/distance, restriction-fragment handling (restrict, Arima dual-enzyme, Micro-C/DNase fragment-free), and allele-specific phasing (pairtools phase to two coolers). The library-QC decision uses % long-range cis as the one-number quality metric, trans as the noise floor, orientation balance as fragment-map-free dangling-end/self-circle QC, and % duplicates as a complexity proxy. Use when processing Hi-C/Micro-C/Omni-C reads into pairs, judging library quality, handling multi-enzyme or restriction-agnostic protocols, or generating allele-specific contacts.

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Aligns and QCs methylated-RNA-immunoprecipitation (MeRIP / m6A-seq) IP and input libraries using STAR or HISAT2 splice-aware mapping, samtools sort/index, IP/input matched-pair tracking, antibody-lot metadata recording, replicate concordance via deepTools multiBamSummary + plotCorrelation, IP enrichment QC via plotFingerprint and per-transcript IP/input ratio distributions, library-complexity saturation curves via PreSeq c_curve / lc_extrap, and the explicit do-NOT-deduplicate convention for standard non-UMI MeRIP. Use when preparing paired IP and input BAM files for exomePeak2 / MeTPeak / MACS3 peak calling, evaluating MeRIP replicate concordance and IP enrichment, deciding whether to deduplicate (standard MeRIP typically NOT — see Tips), choosing genome-vs-transcriptome alignment for downstream peak vs m6Anet workflows, recording antibody clone and lot metadata for downstream cross-batch reconciliation, detecting failed IPs via saturation curves and IP/input distribution shape, or generating IP-over-Input bigWig tracks for downstream visualisation.

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Detects m6A modifications from Oxford Nanopore direct-RNA-sequencing (ONT DRS) signal data using m6Anet (Hendra 2022 *Nat Methods* 19:1590; multiple-instance-learning neural network over DRACH 5-mer signal). Covers the required upstream pipeline (Dorado / Guppy basecalling -> minimap2 transcriptome alignment with `-ax map-ont -uf -k14 --secondary=no` -> nanopolish eventalign with `--scale-events --signal-index` (m6Anet-required) plus `--summary` / `--threads` housekeeping -> m6anet dataprep -> m6anet inference), per-site vs per-read probability interpretation including the `mod_ratio` per-site stoichiometry column, the DRACH-only modeling constraint, minimum-coverage thresholds (20-50 reads per site for stable probability estimates), multi-condition comparison via xPore (Pratanwanich 2021 *Nat Biotechnol* 39:1394), Nanocompore (Leger 2021 *Nat Commun* 12:7198), ELIGOS (Jenjaroenpun 2021 *NAR* 49:e7), and Dorado native modification calling (RNA004 chemistry, 2024+), reference-transcriptome version pinning, the cDNA-vs-DRS chemistry distinction (cDNA-Nanopore CANNOT be used for modification detection), and orthogonal validation against MeRIP / GLORI. Use when calling m6A from ONT DRS without immunoprecipitation, choosing m6Anet vs xPore vs Nanocompore vs ELIGOS vs Dorado native, interpreting per-site `probability_modified` vs `mod_ratio` vs per-read modification probabilities, comparing methylation between conditions from ONT data, deciding between m6Anet for known DRACH sites and Dorado/Remora for genome-wide screening, pinning RNA002 vs RNA004 chemistry and basecaller model versions, or troubleshooting eventalign / dataprep failures.

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Detect positive (diversifying / episodic / pervasive) selection using codon dN/dS frameworks. Implements PAML codeml site models (M0/M1a/M2a/M7/M8/M8a), branch models, branch-site model A (Zhang 2005), and HyPhy methods (BUSTED, BUSTED-S, BUSTED-MH, BUSTED-PH, MEME, FEL, FUBAR, aBSREL, SLAC, RELAX, GARD, FUBAR-MH). Includes McDonald-Kreitman framework (asymptotic alpha, impMKT, polyDFE, DFE-alpha, GRAPES) for within-species + divergence inference, RERconverge for trait-correlated rate shifts, CSUBST for convergent substitution, and PhyloAcc for accelerated noncoding evolution. Use when testing adaptive evolution at codons, branches, or full gene; running GARD recombination pre-screen; controlling alignment-error and gBGC false positives; reconciling PAML vs HyPhy results; or performing genome-scale selection scans.

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Preprocess CLIP-seq reads (eCLIP, iCLIP, iCLIP2, iCLIP3, irCLIP, PAR-CLIP, FLASH) with protocol-specific UMI extraction, adapter trimming, length filtering, and post-alignment PCR-duplicate collapse. Use when raw CLIP FASTQ must be turned into deduplicated, crosslink-preserving BAM input for peak calling; choosing between two-pass and single-pass adapter trimming; deciding minimum read length; or mapping UMI patterns to specific eCLIP/iCLIP/iCLIP2/iCLIP3 library preps.

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Project gene annotations across genomes using TOGA (Kirilenko 2023 whole-genome-alignment chain-based projection with intactness classification), CESAR 2.0 (Sharma & Hiller 2017 codon-aware exon projection), LiftOff (Shumate & Salzberg 2020 reference-based annotation transfer), Liftover (UCSC), GeMoMa (Keilwagen 2019 evidence-based projection), and Comparative Annotation Toolkit (CAT). Use when transferring annotations from a well-annotated reference to query genome(s), classifying gene-loss vs gene-intact across many genomes at scale, building Zoonomia-style comparative annotations across hundreds of mammals or birds (Kirilenko 2023), detecting pseudogenization, projecting alternative isoforms, or selecting between WGA-anchored (TOGA) vs ortholog-based (LiftOff) annotation transfer strategies.

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Infer orthologous genes and gene families across species using OrthoFinder3 (HOG-based phylogenetic orthology), SonicParanoid2, Broccoli, ProteinOrtho, OMA / FastOMA hierarchical orthologous groups, eggNOG-mapper, JustOrthologs, and TOGA whole-genome-alignment orthology. Use when building single-copy ortholog sets for phylogenomics, classifying co-orthologs and in/out-paralogs after gene duplication, propagating functional annotation via orthology with awareness of the ortholog conjecture, distinguishing speciation from duplication via gene-tree species-tree reconciliation, computing Quest-for-Orthologs benchmark performance, or running synteny-aware ortholog detection in WGD-affected lineages.

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Performs 3D shape-based similarity searching using ROCS (OpenEye), USRCAT (ultra-fast), Open3DAlign (RDKit), ESPSim (electrostatic), and ShaEP with explicit handling of Tanimoto-Combo (shape + color), shape vs ECFP4 complementarity, conformer-ensemble searching, alignment optimization, and scaffold hopping. Use when searching for shape-mimicking compounds with different scaffolds, identifying bioisosteric replacements, prospective scaffold hopping, or expanding hit series beyond 2D similarity.

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Calls ChIP-seq peaks with MACS3, MACS2, HOMER, or SPP across narrow (TF) and broad (histone) modes. Handles input control matching, fragment-size modeling vs --nomodel, effective genome size, ENCODE-style IDR vs naive overlap, hyper-ChIPable artifacts, and aligner-specific shifts. Use when calling peaks from ChIP-seq alignments, choosing between narrow vs broad mode for a histone mark, deciding model vs nomodel for low-depth data, applying ENCODE pseudoreplicate IDR, or reconciling MACS vs HOMER vs SPP results.

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Builds and applies 3D pharmacophore models using RDKit Pharm3D, the apo2ph4 receptor-based workflow (Heider et al 2022/2023 J Chem Inf Model 63:147-158), Pharmer / Pharmit (search), and PharmacoForge (diffusion-based generation, Flynn et al 2025 Front Bioinform), covering ligand-based pharmacophore (from active set alignment) and receptor-based pharmacophore (from binding pocket geometry). Explicit handling of feature types, geometric tolerances, partial matching, and pharmacophore-based virtual screening. Use when identifying scaffold-hopping candidates, building shape-and-feature search queries, or transferring SAR across chemotypes.

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Generate consensus sequences and manage reference files using samtools. Use when creating consensus from alignments, indexing references, or creating sequence dictionaries.

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Mark and remove PCR/optical duplicates using samtools fixmate and markdup. Use when preparing alignments for variant calling or when duplicate reads would bias analysis.

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Align protein structures using Foldseek 3Di, TM-align, US-align, DALI, or Foldmason for structural MSA. Predict, score, and superpose backbone coordinates when sequence identity is below the twilight zone or remote-homology detection is required. Use when sequence MSA fails (<25% identity), when the dark proteome is the target, when AlphaFoldDB / ESM Atlas search is needed, or when structural superposition is the goal.

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Trim PCR primers from aligned reads in amplicon-panel BAMs using samtools ampliconclip. Use when processing SARS-CoV-2 ARTIC, hereditary cancer panels, ctDNA hot-spot panels, or any amplicon assay where primer-derived bases would falsely confirm reference at primer footprints.

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Use when the user wants to design, redesign, shape, critique, audit, polish, clarify, distill, harden, optimize, adapt, animate, colorize, extract, or otherwise improve a frontend interface. Covers websites, landing pages, dashboards, product UI, app shells, components, forms, settings, onboarding, and empty states. Handles UX review, visual hierarchy, information architecture, cognitive load, accessibility, performance, responsive behavior, theming, anti-patterns, typography, fonts, spacing, layout, alignment, color, motion, micro-interactions, UX copy, error states, edge cases, i18n, and reusable design systems or tokens. Also use for bland designs that need to become bolder or more delightful, loud designs that should become quieter, live browser iteration on UI elements, or ambitious visual effects that should feel technically extraordinary. Not for backend-only or non-UI tasks.

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Locate CCSPlayer_MovementServices::Pawn in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the local gamedata entry "CCSPlayer_MovementServices::Pawn" (symbol CCSPlayer_MovementServices_Pawn). This is a STRUCT MEMBER OFFSET (schema netvar), not a function. Resolve the CCSPlayer_MovementServices class layout via the schema/network system; the member must satisfy natural alignment. Cross-check with functions that dereference the member. Do not switch output schema: emit the structmember fields below even if the class turns out to be polymorphic - a func_*/vfunc_* payload for this symbol is rejected by canonical_symbol_yaml_bytes. Trigger: CCSPlayer_MovementServices_Pawn, CCSPlayer_MovementServices::Pawn

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Locate CCSBot::Profile in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the local gamedata entry "CCSBot::Profile" (symbol CCSBot_Profile). This is a STRUCT MEMBER OFFSET (schema netvar), not a function. Resolve the CCSBot class layout via the schema/network system; the member must satisfy natural alignment. Cross-check with functions that dereference the member. Do not switch output schema: emit the structmember fields below even if the class turns out to be polymorphic - a func_*/vfunc_* payload for this symbol is rejected by canonical_symbol_yaml_bytes. Trigger: CCSBot_Profile, CCSBot::Profile

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Locate CBaseEntity::m_iTeamNum in CS2 server.dll / libserver.so via IDA Pro MCP and emit a fresh, minimal-unique signature or offset for the local gamedata entry "CBaseEntity::m_iTeamNum" (symbol CBaseEntity_m_iTeamNum). This is a STRUCT MEMBER OFFSET (schema netvar), not a function. Resolve the CBaseEntity class layout via the schema/network system; the member must satisfy natural alignment. Cross-check with functions that dereference the member. Trigger: CBaseEntity_m_iTeamNum, CBaseEntity::m_iTeamNum

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Performs a final quality pass fixing alignment, spacing, consistency, and micro-detail issues before shipping. Use when the user mentions polish, finishing touches, pre-launch review, something looks off, or wants to go from good to great.

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Use when the user wants to design, redesign, shape, critique, audit, polish, clarify, distill, harden, optimize, adapt, animate, colorize, extract, or otherwise improve a frontend interface. Covers websites, landing pages, dashboards, product UI, app shells, components, forms, settings, onboarding, and empty states. Handles UX review, visual hierarchy, information architecture, cognitive load, accessibility, performance, responsive behavior, theming, anti-patterns, typography, fonts, spacing, layout, alignment, color, motion, micro-interactions, UX copy, error states, edge cases, i18n, and reusable design systems or tokens. Also use for bland designs that need to become bolder or more delightful, loud designs that should become quieter, live browser iteration on UI elements, or ambitious visual effects that should feel technically extraordinary. Not for backend-only or non-UI tasks.

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Improve layout, spacing, and visual rhythm. Fixes monotonous grids, inconsistent spacing, and weak visual hierarchy. Use when the user mentions layout feeling off, spacing issues, visual hierarchy, crowded UI, alignment problems, or wanting better composition.

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[62] VALIDATE. Final self-check before delivery. Verify goal alignment, completeness, correctness, and identify residual risks. Produces quality score (0-100) and delivery status. Use when completing any significant work, before handoff, or when you need confidence that work is ready.

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Fine-tune LLMs using reinforcement learning with TRL - SFT for instruction tuning, DPO for preference alignment, PPO/GRPO for reward optimization, and reward model training. Use when need RLHF, align model with preferences, or train from human feedback. Works with HuggingFace Transformers.

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