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Detect and remove doublets from flow and mass cytometry data. Covers FSC/SSC gating and computational doublet detection methods. Use when filtering out cell aggregates before clustering or quantitative analysis.

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Read and manipulate Flow Cytometry Standard (FCS) files. Covers loading data, accessing parameters, and basic data exploration. Use when loading and inspecting flow or mass cytometry data before preprocessing.

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Bead-based normalization for CyTOF and high-parameter flow cytometry. Covers EQ bead normalization, signal drift correction, and batch normalization. Use when correcting instrument drift in CyTOF or harmonizing data across batches.

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Spillover compensation and data transformation for flow cytometry. Covers compensation matrix calculation, application, and biexponential/arcsinh transforms. Use when correcting spectral overlap between fluorophores or transforming data for analysis.

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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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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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Unsupervised clustering and cell type identification for flow/mass cytometry. Covers FlowSOM, Phenograph, and CATALYST workflows. Use when discovering cell populations in high-dimensional cytometry data without predefined gates.

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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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Quality control metrics for ATAC-seq data including fragment size distribution, TSS enrichment, FRiP, and library complexity. Use when assessing ATAC-seq library quality before or after peak calling to identify problematic samples.

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Visualize ChIP-seq data using deepTools, Gviz, and ChIPseeker. Create heatmaps, profile plots, and genome browser tracks. Visualize signal around peaks, TSS, or custom regions. Use when visualizing ChIP-seq signal and peaks.

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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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ChIP-seq quality control metrics including FRiP (Fraction of Reads in Peaks), cross-correlation analysis (NSC/RSC), library complexity, and IDR (Irreproducibility Discovery Rate) for replicate concordance. Use to assess experiment quality before downstream analysis. Use when assessing ChIP-seq data quality metrics.

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Calculate alignment statistics including sequence identity, conservation scores, substitution matrices, and similarity metrics. Use when comparing alignment quality, measuring sequence divergence, and analyzing evolutionary patterns.

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Infer gene regulatory networks (GRNs) from gene expression data using scalable algorithms (GRNBoost2, GENIE3). Use when analyzing transcriptomics data (bulk RNA-seq, single-cell RNA-seq) to identify transcription factor-target gene relationships and regulatory interactions. Supports distributed computation for large-scale datasets.

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Differential binding analysis using DiffBind. Compare ChIP-seq peaks between conditions with statistical rigor. Requires replicate samples. Outputs differentially bound regions with fold changes and p-values. Use when comparing ChIP-seq binding between conditions.

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De novo motif discovery and known motif enrichment analysis using HOMER and MEME-ChIP. Identify transcription factor binding motifs in ChIP-seq, ATAC-seq, or other genomic peak data. Use when finding enriched DNA motifs in peak sequences.

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Convert raw Nanopore signal data (FAST5/POD5) to nucleotide sequences using Dorado basecaller. Covers model selection, GPU acceleration, modified base detection, and quality filtering. Use when processing raw Nanopore data before alignment. Guppy is deprecated; use Dorado for all new analyses.

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Detect transcription factor binding sites through footprinting analysis in ATAC-seq data using TOBIAS. Use when identifying TF occupancy patterns within accessible regions, as TF binding protects DNA from Tn5 cutting.

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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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Guidance for SPR and BLI binding characterization experiments. Use when: (1) Planning binding kinetics experiments, (2) Troubleshooting poor/no binding signal, (3) Interpreting kinetic data artifacts, (4) Choosing between SPR vs BLI platforms.

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Extract nucleosome positions from ATAC-seq data using NucleoATAC, ATACseqQC, and fragment analysis. Use when analyzing chromatin organization, identifying nucleosome-free regions at promoters, or characterizing nucleosome occupancy patterns from ATAC-seq fragment size distributions.

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Call accessible chromatin regions from ATAC-seq data using MACS3 with ATAC-specific parameters. Use when identifying open chromatin regions from aligned ATAC-seq BAM files, different from ChIP-seq peak calling.

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This skill should be used for time series machine learning tasks including classification, regression, clustering, forecasting, anomaly detection, segmentation, and similarity search. Use when working with temporal data, sequential patterns, or time-indexed observations requiring specialized algorithms beyond standard ML approaches. Particularly suited for univariate and multivariate time series analysis with scikit-learn compatible APIs.

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Annotate ChIP-seq peaks to genomic features and genes using ChIPseeker. Assign peaks to promoters, exons, introns, and intergenic regions. Find nearest genes and calculate distance to TSS. Generate annotation plots and statistics. Use when annotating ChIP-seq peaks to genomic features.

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