Normalized and Directional Interplay Scoring for the Interrogation of Proteoform Data.

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Tác giả: Alyssa T Paparella, Karl F Poncha, Nicolas L Young

Ngôn ngữ: eng

Ký hiệu phân loại: 005.452 *Interpreters

Thông tin xuất bản: United States : Journal of proteome research , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 728660

Histone proteoforms, often presenting multiple co-occurring post-translational modifications (PTMs), are central to chromatin regulation and gene expression. A proteoform is a specific form of a protein that includes variations arising from genetic changes, alternative RNA splicing, proteolytic processing, and PTMs. Genome-indexed histone proteoforms define the histone code, influencing cellular phenotype by dictating DNA interacting partners. Understanding the dynamics of histone proteoforms is essential for elucidating chromatin-based regulatory mechanisms. Advances in middle-down and top-down proteomics enable accurate identification and quantitation of thousands of proteoforms in a single run. However, the resulting data complexity presents significant challenges for analysis and visualization. Here, we introduce two new computational methods to analyze the dynamics of histone PTMs and demonstrate their use in mouse organs during aging. The score that we term "normalized interplay" addresses limitations of the original crosstalk score "interplay" providing a more complete and accurate measure of PTM crosstalk. The second score, Δ
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