Chromatin Accessibility Downstream Analysis for High-Confidence Peaks

RStatClub talk at LIBD Institute

These notes focus on strategies and resources for downstream analysis of
chromatin accessibility peaks. The goal is to gather resources to explore/deep on strategies to
identify candidate cis-regulatory elements (cCREs) for advance analysis.

1. Chromatin Accessibility Downstream Analysis for High-Confidence Peaks Notebook: Cynthia SC (08-28-2025) Background These notes focus on strategies and resources for downstream analysis of high-confidence chromatin accessibility peaks. The goal is to gather resources to explore/deep on strategies to identify candidate cis-regulatory elements (cCREs) for advance analysis. Key Literature •​ Chawla et al., 2025 (Nat Genet)​ Single-nucleus chromatin accessibility profiling identifies cell types and functional variants contributing to major depression. DOI link​ Code for DAR (cell-type/cluster-specific cCREs & TFs): GitHub repo •​ Zeng et al., 2024 (Science)​ Genetic regulation of cell type–specific chromatin accessibility shapes brain disease etiology. DOI link •​ Anderson et al., 2023 (Cell Genomics)​ Single nucleus multiomics identifies ZEB1 and MAFB as candidate regulators of Alzheimer’s disease-specific cis-regulatory elements. DOI link​ Code for peak calling: Workflow Vignettes & Tutorials •​ Data structures & object interaction (Signac): Vignette •​ Linking peaks to genes (10x Multiome): Tutorial •​ Calling Peaks with MACS2: Tutorial •​ Motif analysis with Signac: Tutorial •​ Co-accessible networks with Cicero: Tutorial Core Functions & References •​ Signac::CallPeaks → Docs | CRAN •​ GenomicRanges::reduce → Intro | IRanges methods •​ Signac::FeatureMatrix → Docs •​ Signac::RegionStats → Docs •​ Signac::AggregateExpression (Seurat v5+) → Docs
2. •​ Signac::LinkedPeaks → Docs Custom Repo Practices •​ Peak calling workflows: scMultiomics_AD repo •​ Link detection strategies: ◦​ Filter MACS peak calls (e.g., by expression or cell type). ◦​ Keep only genes with sufficient UMIs (e.g., ≥200). ◦​ Restrict peak–gene links by distance (≤100 kb from TSS). ◦​ Example: link filtering. Behind-the-Scenes Tools & File Formats •​ MACS project: GitHub | Changelog •​ Installation: MACS2 guide | MACS3 guide •​ BED file format: UCSC FAQ​