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

作者：Ze Zhang, Paulo Da Silva Cordeiro, Surya B. Chhetri, Brad Fortunato, Zhenjie Jin, Razane El Hajj Chehade, Karl Semaan, Gunsagar S. Gulati, Garyoung Gary Lee, Christopher Hemauer, Weiwei Bian, Shahabeddin Sotudian, Ziwei Zhang, David O. Osei-Hwedieh, Tanya Heim, Corrie Painter, Rashad Nawfal, Marc Eid, Damien Vasseur, John Canniff, Hunter Savignano, Noa Phillips, Ji-Heui Seo, Kurt R. Weiss, Matt Freedman, Sylvan C. Baca · 发表于：bioRxiv (Cold Spring Harbor Laboratory) · 年份：2025 · DOI：10.64898/2025.12.30.694452 · 被引用次数：3 · 研究领域：Cancer Genomics and Diagnostics、Genomics and Chromatin Dynamics、Single-cell and spatial transcriptomics

Epigenomic profiling of circulating chromatin is a powerful and minimally invasive approach for detecting and monitoring disease, but there are no bioinformatics pipelines tailored to the unique characteristics of cell-free chromatin. We present SNAP (Streamlined Nextflow Analysis Pipeline), a reproducible, scalable, and modular workflow specifically designed for immunoprecipitation-based methods for profiling cell-free chromatin. SNAP incorporates quality control metrics optimized for circulating chromatin, including enrichment score and fragment count thresholds, as well as direct estimation of circulating tumor DNA (ctDNA) content from fragment length distributions. It also includes SNP fingerprinting to enable sample identity verification. When applied to cfChIP-seq and cfMeDIP-seq data across multiple cancer types, SNAP's quality filters significantly improved classification performance while maintaining high data retention. Independent validation using plasma from patients with osteosarcoma confirmed the detection of tumor-associated epigenomic signatures that correlated with ctDNA levels and reflected disease biology. SNAP's modular architecture enables straightforward extension to additional cell-free immunoprecipitation-based assays, providing a robust framework to support studies of circulating chromatin broadly. SNAP is compatible with cloud and high-performance computing environments and is publicly available at https://github.com/prc992/SNAP/.