CREPAS: a reproducible nascent DNA sequencing analysis pipeline for epigenome replication studies

Chromatin sequencing data is essential for understanding epigenetic regulation, histone modifications, and the mechanisms underlying epigenetic memory. Techniques like ChIP-seq and ATAC-seq profile DNA-binding proteins and chromatin accessibility, while newer methods such as ChOR-seq and SCAR-seq assess histone modifications and chromatin-associated proteins during and after replication, capturing chromatin states that contribute to memory across cell divisions. Current tools for chromatin data analysis often lack scalability and reproducibility across high-performance computing infrastructures, and available pipelines offer limited parameters, applicable to only a few sequencing techniques. To address these challenges, we developed CREPAS, a Nextflow pipeline for analyzing bulk chromatin sequencing data, including ChIP-seq, ChIP-exo, ChOR-seq, SCAR-seq, OK-seq, ATAC-seq, CUT&RUN, and CUT&Tag. This pipeline integrates nf-core modules and Docker/Singularity containers for accessibility and reproducibility. CREPAS provides an end-to-end solution, from read quality control to advanced analyses, including peak calling, normalization, downsampling, multimapper allocation, and visualization with IGV and MultiQC. It includes calculations like fork directionality and chromatin partitioning for OK-seq or SCAR-seq, linking replication dynamics to epigenetic inheritance. CREPAS is a valuable resource for researchers, enhancing accessibility and efficiency in chromatin sequencing data analysis, while enabling the study of chromatin replication and the propagation of epigenetic states.