NADfinder

NADfinder identifies and characterizes nucleolus-associated domains (NADs) from nucleolus-associated domain sequencing (NAD-seq) data, enabling genome-wide mapping of nucleolus-associated chromatin and analysis of associated heterochromatin features, and is provided as a Bioconductor package.

Key Features:

• Chromosome-level local baseline correction: Implements chromosome-level local baseline correction to improve peak calling accuracy compared with general-purpose tools.
• Full NAD-seq processing workflow: Provides baseline correction, smoothing, normalization, peak calling, and annotation for NAD-seq datasets.
• Cross-condition and cell-type support: Supports robust identification of NADs across diverse experimental conditions and cell types.
• Chromatin feature characterization: Enables analysis of replication timing, H3K9me3 and H3K27me3 enrichment, overlap with lamina-associated domains (LADs), and transcriptional activity associated with NADs.

Scientific Applications:

• Mapping nucleolar genome interactions: Genome-wide identification of genomic regions that physically associate with the nucleolus.
• Chromatin compartmentalization analysis: Comparative analysis of NADs relative to the nuclear lamina and other nuclear substructures.
• NAD classification in MEFs: Identification of Type I NADs that overlap LADs and exhibit late replication, H3K9me3 enrichment, and low transcription, and Type II NADs that associate with nucleoli but not the lamina and show earlier replication, higher expression, and H3K27me3 enrichment.
• Development and disease studies: Investigation of dynamic chromatin reorganization during development and the regulatory relevance of nucleolus-associated chromatin in differentiation and disease.

Methodology:

Computational steps explicitly include chromosome-level local baseline correction, smoothing, normalization, peak calling, and annotation for NAD-seq data.