Untargeted LC-MS metabolomics of bronchoalveolar lavage fluid differentiates acute respiratory distress syndrome from health.
Untargeted LC-MS metabolomics of bronchoalveolar lavage fluid differentiates acute respiratory distress syndrome from health.
复制标题
DOI：
10.1021/pr4007624
复制
发表时间：
2014-02-07
影响因子：
4.4
通讯作者：
Stringer KA
中科院分区：
文献类型：
--
作者：
Evans CR;Karnovsky A;Kovach MA;Standiford TJ;Burant CF;Stringer KA
急性呼吸窘迫综合征(ARDS)是一种严重危害人类健康的疾病，由于目前尚无预测预后的生物标志物和有效的药物治疗，临床上具有挑战性。肺间室代谢组可以详细描述局部环境的状况，这可能有助于ARDS生物标记物的发现和药物靶标机会的确定。然而，无论是将支气管肺泡灌洗液(BALF)作为代谢组学的生物流体还是用于代谢物鉴定的最佳分析平台，都没有建立起来。为了解决这一问题，我们开展了一项研究，使用新开发的非靶向代谢组学液色谱(LC)-质谱学(MS)平台，比较ARDS患者和健康对照组BALF样本中的代谢物。在对三种不同的高效液相色谱柱进行初步测试后，我们确定反相(RP)-LC和亲水相互作用色谱柱(HILIC)是最有信息量的色谱方法，因为它们产生的数据最多、质量最高。在确认代谢物鉴定后，统计分析导致在两个分析平台上ARDS患者的BALF中与健康相比有37种不同的代谢物。通路分析揭示了ARDS BALF中与氨基酸代谢、糖酵解和糖异生、脂肪酸生物合成、磷脂和嘌呤代谢相关的网络。RPLC和HILIC-LC的互补分析平台生成了ARDS肺环境的信息丰富、有洞察力的代谢组学数据。
Acute respiratory distress syndrome (ARDS) remains a significant hazard to human health and is clinically challenging because there are no prognostic biomarkers and no effective pharmacotherapy. The lung compartment metabolome may detail the status of the local environment that could be useful in ARDS biomarker discovery and the identification of drug target opportunities. However, neither the utility of bronchoalveolar lavage fluid (BALF) as a biofluid for metabolomics nor the optimal analytical platform for metabolite identification are established. To address this, we undertook a study to compare metabolites in BALF samples from patients with ARDS and healthy controls using a newly developed liquid chromatography (LC)-mass spectroscopy (MS) platform for untargeted metabolomics. Following initial testing of three different high performance liquid chromatography (HPLC) columns, we determined that reversed phase (RP)-LC and hydrophilic interaction chromatography (HILIC), were the most informative chromatographic methods because they yielded the most and highest quality data. Following confirmation of metabolite identification, statistical analysis resulted in 37 differentiating metabolites in the BALF of ARDS compared with health across both analytical platforms. Pathway analysis revealed networks associated with amino acid metabolism, glycolysis and gluconeogenesis, fatty acid biosynthesis, phospholipids and purine metabolism in the ARDS BALF. The complementary analytical platforms of RPLC and HILIC-LC generated informative, insightful metabolomics data of the ARDS lung environment.
登录
查看更多内容
影响因子：
120.7
作者：
Jones, Alan E.;Shapiro, Nathan I.;Trzeciak, Stephen;Arnold, Ryan C.;Claremont, Heather A.;Kline, Jeffrey A.
通讯作者：
Kline, Jeffrey A.
DOI：
10.1016/j.jchromb.2009.11.040
发表时间：
2010-06-15
影响因子：
3
作者：
Kikuchi, Kaori;Itoh, Yoshiharu;Niwa, Toshimitsu
通讯作者：
Niwa, Toshimitsu
影响因子：
13.6
作者：
Aronov, Pavel A.;Luo, Frank J. -G.;Meyer, Timothy W.
通讯作者：
Meyer, Timothy W.
影响因子：
4.4
作者：
McClay, Joseph L.;Adkins, Daniel E.;van den Oord, Edwin J. C. G.
通讯作者：
van den Oord, Edwin J. C. G.
影响因子：
3.7
作者：
Kuipers, Maria T.;Aslami, Hamid;Wieland, Catharina W.
通讯作者：
Wieland, Catharina W.