SNAP: Streamlined Nextflow Analysis Pipeline for Immunoprecipitation-Based Epigenomic Profiling of Circulating...

Area of Science:

• Genomics
• Bioinformatics
• Molecular Biology

Background:

• Circulating chromatin epigenomic profiling offers a minimally invasive method for disease detection and monitoring.
• Existing bioinformatics pipelines are not optimized for the unique characteristics of cell-free chromatin.

Purpose of the Study:

• To present SNAP (Streamlined Nextflow Analysis Pipeline), a novel bioinformatics workflow tailored for cell-free chromatin epigenomic profiling using immunoprecipitation-based methods.
• To enhance the accuracy and reliability of disease detection and monitoring through optimized analysis of circulating chromatin.

Main Methods:

• Developed SNAP, a reproducible, scalable, and modular Nextflow pipeline.
• Incorporated optimized quality control metrics for circulating chromatin, including enrichment scores and fragment counts.
• Integrated circulating tumor DNA (ctDNA) content estimation and SNP fingerprinting for sample identity verification.

Main Results:

• SNAP demonstrated improved classification performance and high data retention when applied to cfChIP-seq and cfMeDIP-seq data across various cancer types.
• Independent validation in osteosarcoma patients confirmed the detection of tumor-associated epigenomic signatures correlating with ctDNA levels.
• The pipeline successfully identified epigenomic signatures reflecting disease biology.

Conclusions:

• SNAP provides a robust and extensible framework for cell-free chromatin epigenomic studies.
• The pipeline enhances the utility of minimally invasive epigenomic profiling for disease detection, monitoring, and understanding disease biology.
• SNAP is compatible with cloud and high-performance computing environments and is publicly available.