Department of Pathology, University of British Columbia, Vancouver, BC, Canada.
Michael Cuccione Childhood Cancer Research Program, BC Children's Hospital Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada.
Sci Rep. 2021 Nov 18;11(1):22490. doi: 10.1038/s41598-021-01971-3.
The local sequence context is the most fundamental feature determining the post-translational modification (PTM) of proteins. Recent technological improvements allow for the detection of new and less prevalent modifications. We found that established state-of-the-art algorithms for the detection of PTM motifs in complex datasets failed to keep up with this technological development and are no longer robust. To overcome this limitation, we developed RoLiM, a new linear motif deconvolution algorithm and webserver, that enables robust and unbiased identification of local amino acid sequence determinants in complex biological systems demonstrated here by the analysis of 68 modifications found across 30 tissues in the human draft proteome map. Furthermore, RoLiM analysis of a large-scale phosphorylation dataset comprising 30 kinase inhibitors of 10 protein kinases in the EGF signalling pathway identified prospective substrate motifs for PI3K and EGFR.
局部序列上下文是决定蛋白质翻译后修饰（PTM）的最基本特征。最近技术的进步使得能够检测到新的和不太常见的修饰。我们发现，用于在复杂数据集检测 PTM 模体的成熟的最先进算法无法跟上这一技术发展，并且不再稳健。为了克服这一限制，我们开发了 RoLiM，这是一种新的线性基序去卷积算法和网络服务器，它能够稳健和无偏地识别复杂生物系统中的局部氨基酸序列决定因素，在此通过对人类草图蛋白质组图谱中 30 种组织中发现的 68 种修饰的分析进行了展示。此外，对包含在 EGF 信号通路中的 10 个蛋白激酶的 30 种激酶抑制剂的大规模磷酸化数据集进行的 RoLiM 分析，确定了 PI3K 和 EGFR 的预期底物基序。
