Cross-ID: Analysis and Visualization of Complex XL–MS-Driven Protein Interaction Networks

Protein
interactions enable much more complex behavior than the sum of the
individual protein parts would suggest and represents a level of biological
complexity requiring full understanding when unravelling cellular
processes. Cross-linking mass spectrometry has emerged as an attractive
approach to study these interactions, and recent advances in mass
spectrometry and data analysis software have enabled the identification
of thousands of cross-links from a single experiment. The resulting
data complexity is, however, difficult to understand and requires
interactive software tools. Even though solutions are available, these
represent an agglomerate of possibilities, and each features its own
input format, often forcing manual conversion. Here we present Cross-ID,
a visualization platform that links directly into the output of XlinkX
for Proteome Discoverer but also plays well with other platforms by
supporting a user-controllable text-file importer. The platform includes
features like grouping, spectral viewer, gene ontology (GO) enrichment,
post-translational modification (PTM) visualization, domains and secondary
structure mapping, data set comparison, previsualization overlap check,
and more. Validation of detected cross-links is available for proteins
and complexes with known structure or for protein complexes through
the DisVis online platform (http://milou.science.uu.nl/cgi/services/DISVIS/disvis/). Graphs are exportable in PDF format, and data sets can be exported
in tab-separated text files for evaluation through other software.

蛋白质相互作用所介导的复杂行为远超单个蛋白质组分的简单叠加，其所代表的生物学复杂度，是解析细胞进程时亟需全面阐明的核心层面。交联质谱（Cross-linking mass spectrometry）已成为研究此类相互作用的极具吸引力的技术手段，近年来质谱技术与数据分析软件的迭代进步，已实现单次实验中对数千条交联肽段的精准鉴定。然而由此产生的数据复杂度极高，难以直观解析，亟需交互式软件工具的辅助。尽管目前已有相关解决方案，但此类方案多为功能零散的堆砌，且各自拥有专属的输入格式，往往需要人工进行格式转换。为此，本研究推出Cross-ID可视化平台：该平台可直接对接Proteome Discoverer软件中XlinkX模块的输出结果，同时通过支持用户可配置的文本文件导入功能，兼容其他主流分析平台。该平台内置多项核心功能，包括分组管理、谱图查看器、基因本体（Gene Ontology, GO）富集分析、翻译后修饰（Post-translational modification, PTM）可视化、结构域与二级结构映射、数据集比对、预可视化重叠校验等。针对已知结构的蛋白质及复合物，可通过DisVis在线平台（http://milou.science.uu.nl/cgi/services/DISVIS/disvis/）对鉴定得到的交联产物进行有效性验证。生成的可视化图表可导出为PDF格式，数据集则可导出为制表符分隔的文本文件，以供其他软件开展后续评估工作。