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AI-empowered perturbation proteomics for complex biological systems

delete2024-11-01
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OA
AI
L
Liujia Qian
R
Rui Sun
R
Ruedi Aebersold
P
Peter Bühlmann
C
Chris Sander *
T
Tiannan Guo *
DOI:10.1016/j.xgen.2024.100691delete
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Abstract

Abstract

En 中文
The insufficient availability of comprehensive protein-level perturbation data is impeding the widespread adoption of systems biology. In this perspective, we introduce the rationale, essentiality, and practicality of perturbation proteomics. Biological systems are perturbed with diverse biological, chemical, and/or physical factors, followed by proteomic measurements at various levels, including changes in protein expression and turnover, post-translational modifications, protein interactions, transport, and localization, along with phenotypic data. Computational models, employing traditional machine learning or deep learning, identify or predict perturbation responses, mechanisms of action, and protein functions, aiding in therapy selection, compound design, and efficient experiment design. We propose to outline a generic PMMP (perturbation, measurement, modeling to prediction) pipeline and build foundation models or other suitable mathematical models based on large-scale perturbation proteomic data. Finally, we contrast modeling between artificially and naturally perturbed systems and highlight the importance of perturbation proteomics for advancing our understanding and predictive modeling of biological systems.
Keywords:
SPECTROMETRY-BASED PROTEOMICS
PROTEIN STRUCTURAL-CHANGES
SAMPLE PREPARATION METHOD
TARGET IDENTIFICATION
ENVIRONMENTAL-STRESS
CONNECTIVITY MAP
SMALL MOLECULES
EX-VIVO
LANDSCAPE
NETWORK
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Cell Genomics cover
Cell Genomics
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9
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E
ETH Zurich
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swiss federal institutes of technology domain
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westlake university
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