Development and Application of Multidimensional Lipid Libraries to Investigate Lipidomic Dysregulation Related to Smoke Inhalation Injury Severity
Development and Application of Multidimensional Lipid Libraries to Investigate Lipidomic Dysregulation Related to Smoke Inhalation Injury Severity
复制标题
多维脂质库的开发和应用研究与烟雾吸入性损伤严重程度相关的脂质失调
DOI：
10.1101/2021.10.13.464246
复制
发表时间：
2021
期刊：
影响因子：
--
通讯作者：
E. Baker
中科院分区：
文献类型：
--
作者：
K. Kirkwood;Michael W. Christopher;J. Burgess;S. Littau;Brian S. Pratt;Nicholas Shulman;Kaipo Tamura;M. MacCoss;B. MacLean;E. Baker
脂质发挥许多生物学作用，包括膜形成、保护、绝缘、能量储存和细胞分裂。这些功能给脂质组学研究带来了极大的兴趣，以了解它们在毒性暴露、炎症和疾病中的失调。然而，脂质由于其高度异构的性质和在生物基质中的广泛浓度范围而显示出分析上的挑战。因此，强大的多维技术，如集成液相色谱，离子迁移谱，碰撞诱导解离，质谱（LC-IMS-CID-MS），最近已实施分离脂质异构体，以及提供结构信息和增加的特征识别的信心。然而，这些多维数据集非常庞大且高度复杂，导致数据处理和注释方面的挑战。在这里，我们已经克服了这些挑战，通过使用免费提供的软件Skyline开发样本特定的多维库。具体而言，为这项工作开发的人血浆库包含超过500种独特的、实验验证的脂质，其与用于高度置信的脂质注释的适应性Skyline函数相结合，例如用于保留时间预测的索引保留时间（iRT）和用于增加灵敏度和选择性的IMS漂移时间过滤。为了与其他脂质组学研究进行广泛比较，该人血浆数据库最初用于注释NIST SRM 1950提取物的LC-IMS-CID-MS数据，得到与先前研究相当的结果。然后利用该工作流程评估来自不同程度烟雾吸入性损伤患者的匹配血浆和支气管肺泡灌洗液（BALF）样本，以鉴定潜在的基于脂质的患者预后和诊断标志物。
Lipids play many biological roles including membrane formation, protection, insulation, energy storage, and cell division. These functions have brought great interest to lipidomic studies for understanding their dysregulation in toxic exposure, inflammation, and diseases. However, lipids have shown to be analytically challenging due to their highly isomeric nature and vast concentration ranges in biological matrices. Therefore, powerful multidimensional techniques such as those integrating liquid chromatography, ion mobility spectrometry, collision induced dissociation, and mass spectrometry (LC-IMS-CID-MS) have recently been implemented to separate lipid isomers as well as provide structural information and increased feature identification confidence. These multidimensional datasets are however extremely large and highly complex, resulting in challenges in data processing and annotation. Here, we have overcome these challenges by developing sample-specific multidimensional libraries using the freely available software Skyline. Specifically, the human plasma library developed for this work contains over 500 unique, experimentally validated lipids, which is combined with adapted Skyline functions for highly confident lipid annotations such as indexed retention time (iRT) for retention time prediction and IMS drift time filtering for increased sensitivity and selectivity. For broad comparison with other lipidomic studies, this human plasma database was initially used to annotate LC-IMS-CID-MS data from a NIST SRM 1950 extract, giving comparable results to previous studies. This workflow was then utilized to assess matched plasma and bronchoalveolar lavage fluid (BALF) samples from patients with varying degrees of smoke inhalation injury to identify potential lipid-based patient prognostic and diagnostic markers.
登录
查看更多内容
影响因子：
7.4
作者：
Kochen MA;Chambers MC;Holman JD;Nesvizhskii AI;Weintraub ST;Belisle JT;Islam MN;Griss J;Tabb DL
通讯作者：
Tabb DL
影响因子：
7.4
作者：
Kim, Hugh I.;Kim, Hyungjun;Pang, Eric S.;Ryu, Ernest K.;Beegle, Luther W.;Loo, Joseph A.;Goddard, William A.;Kanik, Isik
通讯作者：
Kanik, Isik
影响因子：
7.4
作者：
Stow SM;Causon TJ;Zheng X;Kurulugama RT;Mairinger T;May JC;Rennie EE;Baker ES;Smith RD;McLean JA;Hann S;Fjeldsted JC
通讯作者：
Fjeldsted JC
DOI：
10.1039/c5an02062j
发表时间：
2016-03-07
期刊：
The Analyst
影响因子：
--
作者：
Kyle JE;Zhang X;Weitz KK;Monroe ME;Ibrahim YM;Moore RJ;Cha J;Sun X;Lovelace ES;Wagoner J;Polyak SJ;Metz TO;Dey SK;Smith RD;Burnum-Johnson KE;Baker ES
通讯作者：
Baker ES
影响因子：
5.8
作者：
Kraft, Robert;Herndon, David N.;Jeschke, Marc G.
通讯作者：
Jeschke, Marc G.