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磷酸化蛋白质组学中的深度学习:方法及其在癌症药物发现中的应用

Deep Learning in Phosphoproteomics: Methods and Application in Cancer Drug Discovery.

作者信息

Varshney Neha, Mishra Abhinava K

机构信息

Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California, San Diego, CA 93093, USA.

Ludwig Institute for Cancer Research, La Jolla, CA 92093, USA.

出版信息

Proteomes. 2023 May 2;11(2):16. doi: 10.3390/proteomes11020016.

DOI:10.3390/proteomes11020016
PMID:37218921
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC10204361/
Abstract

Protein phosphorylation is a key post-translational modification (PTM) that is a central regulatory mechanism of many cellular signaling pathways. Several protein kinases and phosphatases precisely control this biochemical process. Defects in the functions of these proteins have been implicated in many diseases, including cancer. Mass spectrometry (MS)-based analysis of biological samples provides in-depth coverage of phosphoproteome. A large amount of MS data available in public repositories has unveiled big data in the field of phosphoproteomics. To address the challenges associated with handling large data and expanding confidence in phosphorylation site prediction, the development of many computational algorithms and machine learning-based approaches have gained momentum in recent years. Together, the emergence of experimental methods with high resolution and sensitivity and data mining algorithms has provided robust analytical platforms for quantitative proteomics. In this review, we compile a comprehensive collection of bioinformatic resources used for the prediction of phosphorylation sites, and their potential therapeutic applications in the context of cancer.

摘要

蛋白质磷酸化是一种关键的翻译后修饰(PTM),是许多细胞信号通路的核心调控机制。几种蛋白激酶和磷酸酶精确地控制着这一生物化学过程。这些蛋白质功能的缺陷与包括癌症在内的许多疾病有关。基于质谱(MS)的生物样品分析可对磷酸化蛋白质组进行深入覆盖。公共数据库中可用的大量MS数据揭示了磷酸化蛋白质组学领域的大数据。为了应对处理大数据以及增强磷酸化位点预测可信度方面的挑战,近年来许多计算算法和基于机器学习的方法得到了快速发展。高分辨率和高灵敏度的实验方法与数据挖掘算法的出现,共同为定量蛋白质组学提供了强大的分析平台。在这篇综述中,我们汇编了用于预测磷酸化位点的生物信息学资源的综合集合,以及它们在癌症背景下的潜在治疗应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a5e/10204361/230c6676077c/proteomes-11-00016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a5e/10204361/56a3b1dbe469/proteomes-11-00016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a5e/10204361/230c6676077c/proteomes-11-00016-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a5e/10204361/56a3b1dbe469/proteomes-11-00016-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2a5e/10204361/230c6676077c/proteomes-11-00016-g002.jpg

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Front Genet. 2022 Oct 21;13:984068. doi: 10.3389/fgene.2022.984068. eCollection 2022.
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Machine learning-assisted elucidation of CD81-CD44 interactions in promoting cancer stemness and extracellular vesicle integrity.机器学习辅助阐明 CD81-CD44 相互作用促进癌症干性和细胞外囊泡完整性。
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Protein Function Analysis through Machine Learning.基于机器学习的蛋白质功能分析。
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KinasePhos 3.0: Redesign and Expansion of the Prediction on Kinase-specific Phosphorylation Sites.KinasePhos 3.0:激酶特异性磷酸化位点预测的重新设计与扩展。
Genomics Proteomics Bioinformatics. 2023 Feb;21(1):228-241. doi: 10.1016/j.gpb.2022.06.004. Epub 2022 Jul 1.
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Individualized Prediction of Drug Response and Rational Combination Therapy in NSCLC Using Artificial Intelligence-Enabled Studies of Acute Phosphoproteomic Changes.利用人工智能实现的急性磷酸化蛋白质组学变化研究对非小细胞肺癌的药物反应和合理联合治疗进行个体化预测。
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