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Copy number normalization distinguishes differential signals driven by copy number differences in ATAC-seq and ChIP-seq

GSE259257 Homo sapiens Genome binding/occupancy profiling by high throughput sequencing 8 samples Submitted 2025/02/17 Platform GPL24676
Summary
A common objective across ATAC-seq and ChIP-seq analyses is to identify differential signals across contrasted conditions. However, in differential analyses, the impact of copy number variation is often overlooked. Here, we demonstrated copy number differences among samples could drive, if not dominate, differential signals. To address this, we propose a pipeline featuring copy number normalization. By comparing the averaged signal per gene copy, it effectively segregates differential signals driven by copy number differences from other factors. Further applying it to Down syndrome, we unveiled distinct dosage-dependent and -independent changes on chromosome 21. Thus, we recommend normalization as a general approach.
Published in
Copy number normalization distinguishes differential signals driven by copy number differences in ATAC-seq and ChIP-seq
Su D, Peters M, Soltys V et al. · BMC genomics 2025 · PMID 40155863 · doi:10.1186/s12864-025-11442-y
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Also filed as BioProject PRJNA1080546 and SRA study SRP491763. Searching any of these in the dataset finder brings you back here.

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