Nature Structural & Molecular Biology· 2026Q1
A phosphoproteome atlas of human cell lines reveals the landscape of kinase activity
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- Q1SCImago
- 2026year
Short summary
A new phosphoproteome atlas of 33 human cell lines, containing over 200,000 phosphosites, dramatically improves phosphoproteomics data processing speed (30x faster) and phosphosite identification confidence, even with low sample input.
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Key points
- A new resource contains over 200,000 class I phosphosites from 33 diverse human cell lines.
- The spectral library improves single-shot phosphoproteomics, achieving 30-fold faster data processing than library-free methods.
- It enhances phosphosite localization confidence, particularly with low sample input.
- A combined kinase activity score (Cscore) was developed, highlighting cell-specific signaling vulnerabilities and drug sensitivity correlations.
AI-generated from the title and abstract; the full text is not read.
Abstract
Abstract Protein phosphorylation orchestrates cellular signaling and controls most biological processes, with its dysregulation driving diseases, notably cancer. Comprehensive, high-throughput phosphoproteomics remains limited by detection sensitivity, data completeness and computational bottlenecks, especially in low-input settings. Here we present a comprehensive empirical human phosphoproteome resource, regrouping over 200,000 class I phosphosites across 33 diverse human cell lines. We demonstrate that this spectral library dramatically improves single-shot phosphoproteomics with 30-fold faster data processing compared with library-free approaches and enhances confidence in phosphosite localization even from minimal sample input. Integrating proteome and phosphoproteome data, we develop a combined kinase activity score (Cscore), revealing cell line- and cancer-specific signaling vulnerabilities, many correlating with drug sensitivity. This resource accelerates deep and reproducible phosphoproteomics, enables the systematic mapping of cellular signaling networks and may empower precision oncology by highlighting actionable kinase targets in diverse cell states.
The authors' abstract, as published at the source. Nature Structural & Molecular Biology, 2026 · DOI ↗
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Field: Spectroscopy
SpectroscopyChemistry