15 years of PhosphoSitePlus®: integrating post-translationally modified sites, disease variants and isoforms
15 years of PhosphoSitePlus®: integrating post-translationally modified sites, disease variants and isoforms
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DOI：
10.1093/nar/gky1159
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发表时间：
2019-01-08
影响因子：
14.9
通讯作者：
Gnad, Florian
中科院分区：
文献类型：
--
作者：
Hornbeck, Peter V.;Kornhauser, Jon M.;Gnad, Florian
15年来，PhosphoSitePlus（（R））（PSP，https://www.phosphosite.org）的使命一直是为哺乳动物翻译后修饰（PTM）的研究提供全面的信息和工具。PSP中唯一PTM的数量现在超过450000，来自22000多篇文章和数千个MS数据集。PSP最重要的增长领域是疾病和亚型信息学。与遗传性疾病和体细胞癌突变相关的生殖系突变已被添加到数据库中，并且现在可以与PTM一起沿着查看，并在新的棒棒糖图上提供相关的定量信息。这些图使研究人员能够交互式地可视化疾病变体和PTM之间的重叠，并通过重新连接信号网络来识别可能改变表型的突变。我们正在扩大序列空间，包括超过30000人类和小鼠的异构体，使研究人员能够探索重要的，但未充分研究的生物学异构体。这代表了序列空间的必要扩展，以适应质谱法不断进步所带来的日益增长的精度和覆盖深度。使用新的算法对同种型进行比对。在整个亚型空间中探索PTM和疾病突变的世界将有望导致新的生物标志物，治疗靶点和对亚型生物学的见解。
For 15 years the mission of PhosphoSitePlus((R)) (PSP, https://www.phosphosite.org) has been to provide comprehensive information and tools for the study of mammalian post-translational modifications (PTMs). The number of unique PTMs in PSP is now more than 450000 from over 22000 articles and thousands of MS datasets. The most important areas of growth in PSP are in disease and isoform informatics. Germline mutations associated with inherited diseases and somatic cancer mutations have been added to the database and can now be viewed along with PTMs and associated quantitative information on novel lollipop' plots. These plots enable researchers to interactively visualize the overlap between disease variants and PTMs, and to identify mutations that may alter phenotypes by rewiring signaling networks. We are expanding the sequence space to include over 30000 human and mouse isoforms to enable researchers to explore the important but understudied biology of isoforms. This represents a necessary expansion of sequence space to accommodate the growing precision and depth of coverage enabled by ongoing advances in mass spectrometry. Isoforms are aligned using a new algorithm. Exploring the worlds of PTMs and disease mutations in the entire isoform space will hopefully lead to new biomarkers,therapeutic targets, and insights into isoform biology.