Filter and prioritize variants by pathogenicity, population frequency, and clinical evidence for rare disease analysis. Use when identifying candidate disease-causing variants from exome or genome sequencing.
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Filter and prioritize variants by pathogenicity, population frequency, and clinical evidence for rare disease analysis. Use when identifying candidate disease-causing variants from exome or genome sequencing.
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CRISPR library design for genetic screens. Covers sgRNA selection, library composition, control design, and oligo ordering. Use when designing custom sgRNA libraries for knockout, activation, or interference screens.
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Perform differential expression analysis using DESeq2 in R/Bioconductor. Use for analyzing RNA-seq count data, creating DESeqDataSet objects, running the DESeq workflow, and extracting results with log fold change shrinkage. Use when performing DE analysis with DESeq2.
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Detect A/B compartments from Hi-C data using cooltools and eigenvector decomposition. Identify active (A) and inactive (B) chromatin compartments from contact matrices. Use when identifying A/B compartments from Hi-C data.
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Analyze time-series RNA-seq data using limma voom with splines, maSigPro, and ImpulseDE2. Identify genes with dynamic expression patterns. Use when analyzing time-series or longitudinal expression data.
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Design pegRNAs for prime editing using PrimeDesign algorithms. Generate spacer, PBS, and RT template sequences for precise genomic modifications without double-strand breaks. Use when designing prime editing experiments for precise insertions, deletions, or point mutations.
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Statistical methods for calling hits in CRISPR screens. Covers MAGeCK, BAGEL2, drugZ, and custom approaches for identifying essential and resistance genes. Use when identifying significant genes from screen count data after QC passes.
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Design homology-directed repair donor templates for CRISPR knock-ins using primer3-py. Create ssODN, dsDNA, or plasmid templates with optimized homology arms. Use when designing donor templates for precise insertions, tagging, or allele replacement.
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Analyzes base editing and prime editing outcomes including editing efficiency, bystander edits, and indel frequencies. Use when quantifying CRISPR base editor results, comparing ABE vs CBE efficiency, or assessing prime editing fidelity.
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Extract, filter, annotate, and export differential expression results from DESeq2 or edgeR. Use for identifying significant genes, applying multiple testing corrections, adding gene annotations, and preparing results for downstream analysis. Use when filtering and exporting DE analysis results.
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Load, convert, and manipulate Hi-C contact matrices using cooler format. Read .cool/.mcool files, convert from .hic format, access matrix data, and export to different formats. Use when loading or converting Hi-C contact matrices.
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Calculate tumor mutational burden from panel or WES data with proper normalization and clinical thresholds. Use when assessing immunotherapy eligibility or characterizing tumor immunogenicity.
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Generate consensus FASTA sequences by applying VCF variants to a reference using bcftools consensus. Use when creating sample-specific reference sequences or reconstructing haplotypes.
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JACKS (Joint Analysis of CRISPR/Cas9 Knockout Screens) for modeling sgRNA efficacy and gene essentiality. Use when analyzing multiple CRISPR screens simultaneously or when accounting for variable sgRNA efficiency across experiments.
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Detect copy number variants from targeted/exome sequencing using CNVkit. Supports tumor-normal pairs, tumor-only, and germline CNV calling. Use when detecting CNVs from WES or targeted panel sequencing data.
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Call copy number variants using GATK best practices workflow. Supports both somatic (tumor-normal) and germline CNV detection from WGS or WES data. Use when following GATK best practices or integrating CNV calling with other GATK variant pipelines.
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Batch effect correction for CRISPR screens. Covers normalization across batches, technical replicate handling, and batch-aware analysis. Use when combining screens from multiple batches or correcting systematic technical variation.
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CRISPResso2 for analyzing CRISPR gene editing outcomes. Quantifies indels, HDR efficiency, and generates comprehensive editing reports. Use when analyzing amplicon sequencing data from CRISPR editing experiments to assess editing efficiency.
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Parse and analyze multiple sequence alignments using Biopython. Extract sequences, identify conserved regions, analyze gaps, work with annotations, and manipulate alignment data for downstream analysis. Use when parsing or manipulating multiple sequence alignments.
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Query BindingDB for measured drug-target binding affinities (Ki, Kd, IC50, EC50). Search by target (UniProt ID), compound (SMILES/name), or pathogen. Essential for drug discovery, lead optimization, polypharmacology analysis, and structure-activity relationship (SAR) studies.
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Query ClinVar for variant pathogenicity classifications, review status, and disease associations via REST API or local VCF. Use when determining clinical significance of variants for diagnostic or research purposes.
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Access AlphaFold's 200M+ AI-predicted protein structures. Retrieve structures by UniProt ID, download PDB/mmCIF files, analyze confidence metrics (pLDDT, PAE), for drug discovery and structural biology.
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Estimate causal effects between exposures and outcomes using genetic variants as instrumental variables with TwoSampleMR. Implements IVW, MR-Egger, weighted median, and MR-PRESSO methods for robust causal inference from GWAS summary statistics. Use when testing whether an exposure causally affects an outcome using genetic instruments.
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This skill should be used when working with annotated data matrices in Python, particularly for single-cell genomics analysis, managing experimental measurements with metadata, or handling large-scale biological datasets. Use when tasks involve AnnData objects, h5ad files, single-cell RNA-seq data, or integration with scanpy/scverse tools.
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