Bland Garret D, Abrahamsson Dimitri, Wang Miaomiao, Zlatnik Marya G, Morello-Frosch Rachel, Park June-Soo, Sirota Marina, Woodruff Tracey J
Department of Obstetrics, Gynecology and Reproductive Sciences, Program on Reproductive Health and the Environment, University of California San Francisco, San Francisco, CA, United States.
Department of Obstetrics, Gynecology and Reproductive Sciences, Program on Reproductive Health and the Environment, University of California San Francisco, San Francisco, CA, United States.
Sci Total Environ. 2024 Feb 20;912:169458. doi: 10.1016/j.scitotenv.2023.169458. Epub 2023 Dec 22.
Capturing the breadth of chemical exposures in utero is critical in understanding their long-term health effects for mother and child. We explored methodological adaptations in a Non-Targeted Analysis (NTA) pipeline and evaluated the effects on chemical annotation and discovery for maternal and infant exposure. We focus on lesser-known/underreported chemicals in maternal and umbilical cord serum analyzed with liquid chromatography-quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The samples were collected from a demographically diverse cohort of 296 maternal-cord pairs (n = 592) recruited in San Francisco Bay area. We developed and evaluated two data processing pipelines, primarily differing by detection frequency cut-off, to extract chemical features from non-targeted analysis (NTA). We annotated the detected chemical features by matching with EPA CompTox Chemicals Dashboard (n = 860,000 chemicals) and Human Metabolome Database (n = 3140 chemicals) and applied a Kendrick Mass Defect filter to detect homologous series. We collected fragmentation spectra (MS/MS) on a subset of serum samples and matched to an experimental MS/MS database within the MS-Dial website and other experimental MS/MS spectra collected from standards in our lab. We annotated ~72 % of the features (total features = 32,197, levels 1-4). We confirmed 22 compounds with analytical standards, tentatively identified 88 compounds with MS/MS spectra, and annotated 4862 exogenous chemicals with an in-house developed annotation algorithm. We detected 36 chemicals that appear to not have been previously reported in human blood and 9 chemicals that were reported in less than five studies. Our findings underline the importance of NTA in the discovery of lesser-known/unreported chemicals important to characterize human exposures.
了解子宫内化学物质暴露的广度对于理解其对母婴长期健康的影响至关重要。我们探索了非靶向分析（NTA）流程中的方法调整，并评估了对母婴暴露化学物质注释和发现的影响。我们重点关注通过液相色谱-四极杆飞行时间质谱（LC-QTOF/MS）分析的母血和脐带血血清中鲜为人知/报道较少的化学物质。样本来自旧金山湾区招募的296对母婴（n = 592）的人口统计学多样化队列。我们开发并评估了两种数据处理流程，主要区别在于检测频率截止值，以从非靶向分析（NTA）中提取化学特征。我们通过与美国环境保护局综合毒理学化学物质仪表板（n = 860,000种化学物质）和人类代谢组数据库（n = 3140种化学物质）匹配来注释检测到的化学特征，并应用肯德里克质量缺陷过滤器来检测同系物系列。我们在一部分血清样本上收集了碎片谱（MS/MS），并与MS-Dial网站内的实验MS/MS数据库以及我们实验室从标准品收集的其他实验MS/MS谱进行匹配。我们注释了约72%的特征（总特征数 = 32,197，1-4级）。我们用分析标准品确认了22种化合物，用MS/MS谱初步鉴定了88种化合物，并用自行开发的注释算法注释了4862种外源性化学物质。我们检测到36种似乎以前未在人类血液中报道过的化学物质和9种在不到五项研究中报道过的化学物质。我们的研究结果强调了NTA在发现对表征人类暴露很重要的鲜为人知/未报道的化学物质方面的重要性。
