dbPTM in 2019: exploring disease association and cross-talk of post-translational modifications
dbPTM in 2019: exploring disease association and cross-talk of post-translational modifications
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DOI：
10.1093/nar/gky1074
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发表时间：
2019-01-08
影响因子：
14.9
通讯作者：
Huang, Hsien-Da
中科院分区：
文献类型：
--
作者：
Huang, Kai-Yao;Lee, Tzong-Yi;Huang, Hsien-Da
dbPTM（http：//dbPTM.mbc.nctu.edu.tw/）已维护了10多年，旨在为翻译后修饰（PTM）提供功能和结构分析。在本次更新中，dbPTM不仅整合了来自可用数据库和通过手动整理文献的更多实验验证的PTM，还提供了基于非同义单核苷酸多态性（nsSNP）的PTM-疾病关联。高通量深度测序技术导致通过分析SNP与疾病之间的关联而产生的数据激增，无论是在增长量还是范围方面。因此，该更新基于全基因组关联研究从dbSNP整合了疾病相关的nsSNP。根据nsSNPs编码的氨基酸，位于特定距离处的PTM底物位点被认为与所涉及的疾病相关。近年来，越来越多的证据之间的串扰PTM已被报道。虽然质谱为基础的蛋白质组学已经大大提高了我们的知识底物位点特异性的单一PTM，组合PTM的串扰可能会与蛋白质的功能和活性的调节一致的事实被忽视。由于关于PTM串扰的并发频率和功能相关性的信息相对有限，在此更新中，在指定的窗口长度内与其他PTM位点相邻的PTM位点进行基序发现和功能富集分析。本次更新强调了PTM串扰研究中当前的挑战，并打破了蛋白质组学如何有助于理解PTM代码的瓶颈，揭示了未来PTM研究中数据复杂性和蛋白质组学限制的新水平。
The dbPTM (http://dbPTM.mbc.nctu.edu.tw/) has been maintained for over 10 years with the aim to provide functional and structural analyses for post-translational modifications (PTMs). In this update, dbPTM not only integrates more experimentally validated PTMs from available databases and through manual curation of literature but also provides PTM-disease associations based on non-synonymous single nucleotide polymorphisms (nsSNPs). The high-throughput deep sequencing technology has led to a surge in the data generated through analysis of association between SNPs and diseases, both in terms of growth amount and scope. This update thus integrated disease-associated nsSNPs from dbSNP based on genome-wide association studies. The PTM substrate sites located at a specified distance in terms of the amino acids encoded from nsSNPs were deemed to have an association with the involved diseases. In recent years, increasing evidence for crosstalk between PTMs has been reported. Although mass spectrometry-based proteomics has substantially improved our knowledge about substrate site specificity of single PTMs, the fact that the crosstalk of combinatorial PTMs may act in concert with the regulation of protein function and activity is neglected. Because of the relatively limited information about concurrent frequency and functional relevance of PTM crosstalk, in this update, the PTM sites neighboring other PTM sites in a specified window length were subjected to motif discovery and functional enrichment analysis. This update highlights the current challenges in PTM crosstalk investigation and breaks the bottleneck of how proteomics may contribute to understanding PTM codes, revealing the next level of data complexity and proteomic limitation in prospective PTM research.