MaXLinker: proteome-wide cross-link identifications with high specificity and sensitivity.

MaXLinker: proteome-wide cross-link identifications with high specificity and sensitivity. Mol Cell Proteomics. 2019 Dec 15;: Authors: Yugandhar K, Wang TY, Leung AK, Lanz MC, Motorykin I, Liang J, Shayhidin EE, Smolka MB, Zhang S, Yu H Abstract Protein-protein interactions play a vital role in nearly all cellular functions. Hence, understanding their interaction patterns and three-dimensional structural conformations can provide crucial insights about various biological processes and underlying molecular mechanisms for many disease phenotypes. Cross-linking mass spectrometry (XL-MS) has the unique capability to detect protein-protein interactions at a large scale along with spatial constraints between interaction partners. The inception of MS-cleavable cross-linkers enabled the MS2-MS3 XL-MS acquisition strategy that provides cross-link information from both MS2 and MS3 level. However, the current cross-link search algorithm available for MS2-MS3 strategy that follow an "MS2-centric" approach, suffer from a high rate of mis-identified cross-links. We demonstrate the problem with the help of two new quality assessment metrics ('fraction of mis-identifications' (FMI) and 'fraction of interprotein cross-links from known interactions' (FKI)). We then address this problem, by designing a novel "MS3-centric" approach for cross-link identification and implementing it as a search engine called MaXLinker. MaXLinker significantly outperforms ...
Source: Molecular and Cellular Proteomics : MCP - Category: Molecular Biology Authors: Tags: Mol Cell Proteomics Source Type: research