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

Zhang, Z.; Da Silva Cordeiro, P.; Chhetri, S. B.; Fortunato, B.; Jin, Z.; El Hajj Chehade, R.; Semaan, K.; Gulati, G.; Lee, G. G.; Hemauer, C.; Bian, W.; Sotudian, S.; Osei-Hwedieh, D.; Heim, T. E.; Painter, C.; Nawfal, R.; Eid, M.; Vasseur, D.; Canniff, J.; Savignano, H.; Phillips, N.; Seo, J.-H.; Weiss, K. R.; Freedman, M. L.; Baca, S. C.

doi:10.64898/2025.12.30.694452

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bioRxiv · 10.64898/2025.12.30.694452

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

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Abstract

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, SNAPs 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. SNAPs 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/. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/694452v1_ufig1.gif" ALT="Figure 1"> View larger version (20K): org.highwire.dtl.DTLVardef@47c734org.highwire.dtl.DTLVardef@674af8org.highwire.dtl.DTLVardef@16ae938org.highwire.dtl.DTLVardef@1f57a01_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Zhang, Z., Da Silva Cordeiro, P., Chhetri, S. B., Fortunato, B., Jin, Z., El Hajj Chehade, R., Semaan, K., Gulati, G., Lee, G. G., Hemauer, C., Bian, W., Sotudian, S., Osei-Hwedieh, D., Heim, T. E., Painter, C., Nawfal, R., Eid, M., Vasseur, D., Canniff, J., Savignano, H., Phillips, N., Seo, J.-H., Weiss, K. R., Freedman, M. L., Baca, S. C.. 2025-12-30. SNAP: Streamlined Nextflow Analysis Pipeline for Immunoprecipitation-Based Epigenomic Profiling of Circulating Chromatin. https://doi.org/10.64898/2025.12.30.694452

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