signac-chromatin-analysis

Analyzes 10x Multiome scATAC-seq data in R with Signac, from TF-IDF and LSI to ChromVAR motif enrichment.

1|Updated Nov 20, 2025
One-click install
npx skills add https://github.com/tony-zhelonkin/scio --skill signac-chromatin-analysis-tony-zhelonkin
Or copy as Structured Prompt for Agent▼
Please help me install this Agent Skill.
Skill: signac-chromatin-analysis
Source: https://github.com/tony-zhelonkin/scio/tree/main/skills/signac-chromatin-analysis
Command: npx skills add https://github.com/tony-zhelonkin/scio --skill signac-chromatin-analysis-tony-zhelonkin

SYSTEM DOCUMENTATION & REQUIREMENTS

What problem does it solve? Analyzing chromatin accessibility from 10x Multiome RNA+ATAC data requires coordinating many specialized steps — fragment loading, TSS enrichment QC, TF-IDF/LSI reduction, WNN integration, motif analysis, and peak-gene linkage — and mistakes like using a depth-correlated LSI component silently corrupt downstream results. ## Core Features & Use Cases - Multiome QC and preprocessing: Load 10x Cell Ranger outputs into a Seurat object with a ChromatinAssay, compute nucleosome signal and TSS enrichment, and filter low-quality cells. - Joint RNA+ATAC analysis: Run TF-IDF + LSI on peaks, SCTransform + PCA on RNA, and integrate both modalities with weighted nearest neighbors (WNN). - Regulatory genomics: Compute gene activity scores, differential accessibility with logistic regression, ChromVAR motif enrichment with JASPAR, peak-gene linkage, and locus-level coverage plots. - Use Case: Given a 10x Multiome experiment on PBMCs, build a WNN UMAP, identify B-cell vs T-cell differential peaks, and visualize CTCF motif activity and MS4A1 locus coverage. ## Quick Start Use the Signac workflow to load my filtered_feature_bc_matrix.h5 and atac_fragments.tsv.gz files, run QC and WNN integration, and produce a coverage plot for the MS4A1 locus.

Frequently Asked Questions about signac-chromatin-analysis

High-intent search queries and answers about installing and using this skill.

FAQPage Schema
How do I analyze 10x Multiome RNA and ATAC data in R?▼

Load the filtered feature-barcode matrix with Read10X_h5, create a Seurat object for RNA and a ChromatinAssay for peaks with the fragments file, then run SCTransform on RNA and TF-IDF plus LSI on ATAC before integrating both with FindMultiModalNeighbors for a WNN UMAP.

Signac vs snapATAC2 for scATAC-seq analysis?▼

Signac is the R-based choice that integrates directly with Seurat for joint RNA+ATAC WNN analysis, while snapATAC2 is the Python alternative. Use Signac when your workflow is Seurat-centric; use snapatac2-atac-preprocessing for Python pipelines.

Why should I exclude LSI component 1 in scATAC-seq analysis?▼

The first LSI component frequently correlates with sequencing depth rather than biology. Run DepthCor() to check, and if correlated, use dims 2:N in all downstream steps such as WNN integration and clustering.

Why does RunChromVAR fail in Signac?▼

RunChromVAR fails when the genome package chromosome naming style does not match the annotation. Ensure seqlevelsStyle of the EnsDb annotations is set consistently (e.g., UCSC) with the BSgenome package used for motif analysis.

How do I link ATAC peaks to genes in Signac?▼

Run RegionStats followed by LinkPeaks with the ATAC peak assay and the normalized RNA assay, optionally restricting to genes of interest. Visualize the resulting links overlaid on a CoveragePlot of the locus.

When should I not use Signac for chromatin analysis?▼

Do not use Signac for Python-based ATAC workflows, where snapATAC2 is appropriate, or for CITE-seq protein plus RNA analysis, where the seurat-citeseq-wnn workflow applies. Signac targets scATAC-seq and 10x Multiome data in R.