Moving translational mass spectrometry imaging towards transparent and reproducible data analyses: a case study of an urothelial cancer cohort analyzed in the Galaxy framework.
Moving translational mass spectrometry imaging towards transparent and reproducible data analyses: a case study of an urothelial cancer cohort analyzed in the Galaxy framework.
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DOI：
10.1186/s12014-022-09347-z
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发表时间：
2022-04-19
影响因子：
3.8
通讯作者：
中科院分区：
文献类型：
--
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质谱成像（MSI）直接从临床组织标本中获取空间分子分布图，因此在协助病理学家做出诊断决策或个性化治疗方面具有巨大潜力。不幸的是，翻译 MSI 的进展常常因质量控制不足和缺乏可重复的数据分析而受到阻碍。原始数据和分析脚本很少公开共享。在这里，我们演示了 Galaxy MSI 工具集在尿路上皮癌数据集的可重复分析中的应用。使用 MALDI-TOF/TOF 装置对一组 39 个福尔马林固定、石蜡包埋的人尿路上皮癌组织核心进行胰蛋白酶肽成像。完整的数据分析是在欧洲银河服务器上以完全透明且可重复的方式进行的。肿瘤和基质的注释由病理学家进行，并转移到 MSI 数据中，以便对肿瘤与基质组织区域以及肌肉浸润性和非肌肉浸润性尿路上皮癌进行监督分类。对于假定的肽鉴定，m/z 特征与 MSiMass 列表相匹配。严格的质量控制与仔细的预处理相结合，可以减少 m/z 偏移和强度批次效应。肿瘤与间质以及肌肉浸润性与非肌肉浸润性尿路上皮肿瘤均具有较高的分类准确性。每种情况下一些最具辨别力的 m/z 特征可以被指定一个假定的身份：基质组织的特征是胶原蛋白肽，肿瘤组织的特征是组蛋白肽。免疫组织化学证实与基质组织相比，肿瘤中组蛋白 H2A 丰度增加。肌肉浸润状态通过 MSI 通过来自中间丝的肽来区分，例如非肌肉浸润性癌中的细胞角蛋白 7 和肌肉浸润性尿路上皮癌中的波形蛋白，并通过免疫组织化学证实。为了使研究完全可重复并倡导 FAIR（可查找性、可访问性、互操作性和可重用性）研究数据的标准，我们共享原始数据、光谱注释以及所有 Galaxy 历史和工作流程。数据可通过 ProteomeXchange 获取，标识符为 PXD026459，Galaxy 结果可通过 https://github.com/foellmelanie/Bladder_MSI_Manuscript_Galaxy_links 获取。在这里，我们证明以完全透明和可重复的方式进行转化 MSI 数据分析是可能的，我们希望鼓励社区加入我们的努力。
Mass spectrometry imaging (MSI) derives spatial molecular distribution maps directly from clinical tissue specimens and thus bears great potential for assisting pathologists with diagnostic decisions or personalized treatments. Unfortunately, progress in translational MSI is often hindered by insufficient quality control and lack of reproducible data analysis. Raw data and analysis scripts are rarely publicly shared. Here, we demonstrate the application of the Galaxy MSI tool set for the reproducible analysis of a urothelial carcinoma dataset. Tryptic peptides were imaged in a cohort of 39 formalin-fixed, paraffin-embedded human urothelial cancer tissue cores with a MALDI-TOF/TOF device. The complete data analysis was performed in a fully transparent and reproducible manner on the European Galaxy Server. Annotations of tumor and stroma were performed by a pathologist and transferred to the MSI data to allow for supervised classifications of tumor vs. stroma tissue areas as well as for muscle-infiltrating and non-muscle infiltrating urothelial carcinomas. For putative peptide identifications, m/z features were matched to the MSiMass list. Rigorous quality control in combination with careful pre-processing enabled reduction of m/z shifts and intensity batch effects. High classification accuracy was found for both, tumor vs. stroma and muscle-infiltrating vs. non-muscle infiltrating urothelial tumors. Some of the most discriminative m/z features for each condition could be assigned a putative identity: stromal tissue was characterized by collagen peptides and tumor tissue by histone peptides. Immunohistochemistry confirmed an increased histone H2A abundance in the tumor compared to the stroma tissues. The muscle-infiltration status was distinguished via MSI by peptides from intermediate filaments such as cytokeratin 7 in non-muscle infiltrating carcinomas and vimentin in muscle-infiltrating urothelial carcinomas, which was confirmed by immunohistochemistry. To make the study fully reproducible and to advocate the criteria of FAIR (findability, accessibility, interoperability, and reusability) research data, we share the raw data, spectra annotations as well as all Galaxy histories and workflows. Data are available via ProteomeXchange with identifier PXD026459 and Galaxy results via https://github.com/foellmelanie/Bladder_MSI_Manuscript_Galaxy_links. Here, we show that translational MSI data analysis in a fully transparent and reproducible manner is possible and we would like to encourage the community to join our efforts.
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影响因子：
7
作者：
Kriegsmann, Mark;Casadonte, Rita;Weichert, Wilko
通讯作者：
Weichert, Wilko
影响因子：
11.5
作者：
Cazares, Lisa H.;Troyer, Dean;Semmes, O. John
通讯作者：
Semmes, O. John
影响因子：
9.2
作者：
Foell, Melanie Christine;Moritz, Lennart;Schilling, Oliver
通讯作者：
Schilling, Oliver
影响因子：
4.3
作者：
Deininger, Soeren-Oliver;Cornett, Dale S.;Paape, Rainer;Becker, Michael;Pineau, Charles;Rauser, Sandra;Walch, Axel;Wolski, Eryk
通讯作者：
Wolski, Eryk
影响因子：
4.4
作者：
McDonnell, Liam A.;Walch, Axel;Corthals, Garry L.
通讯作者：
Corthals, Garry L.