Integrative exposomic, transcriptomic, epigenomic analyses of human placental samples links understudied chemicals to preeclampsia.
Integrative exposomic, transcriptomic, epigenomic analyses of human placental samples links understudied chemicals to preeclampsia.
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DOI：
10.1016/j.envint.2022.107385
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发表时间：
2022-09
影响因子：
11.8
通讯作者：
Rager, Julia E.
中科院分区：
文献类型：
--
作者：
Chao, Alex;Grossman, Jarod;Carberry, Celeste;Lai, Yunjia;Williams, Antony J.;Minucci, Jeffrey M.;Purucker, S. Thomas;Szilagyi, John;Lu, Kun;Boggess, Kim;Fry, Rebecca C.;Sobus, Jon R.;Rager, Julia E.
环境健康研究最近经历了一个巨大的转变，不断的技术进步允许更广泛的接触和分子生物学特征的覆盖面。仍然需要采取综合这些措施的办法，以增进对系统一级接触与生物学之间的了解。我们通过评估胎盘组织来确定与先兆子痫相关的新的化学-生物学相互作用来解决这一差距。这项研究测试了一个假设，即研究不足的化学物质存在于人类胎盘中，并与先兆子痫相关的破坏，包括整体情况下的状态（先兆子痫与血压正常的患者）和潜在的转录组/表观基因组签名。使用基于高分辨率质谱的非靶向分析来分析来自患有先兆子痫（n = 18）和血压正常（n = 17）妊娠的35名患者的队列的胎盘组织。根据与先兆子痫病例状态的相关性和化学鉴定的置信度，对分子特征数据进行优先确认。评估所有分子特征与mRNA、microRNA和CpG甲基化的关系（即，多组学）信号改变。共有183个分子特征被鉴定为在先兆子痫患者的胎盘提取物中具有显著差异的丰度;这些特征使用非监督方法聚类成不同的化学分组。在这些特征中，使用化学标准品、碎片光谱和化学元数据确定了53种特征（映射到40种不同的化学品）。一般来说，人类代谢物具有最大的特征强度，与先兆子痫相关的多组学变化的关联性最强。外源性药物是第二丰富的，与多组学变化的关联较少。其他外源性化学物质（非药物）最不丰富，与多组学变化的关联最少。这些全球数据趋势表明，人类代谢物与先兆子痫病因学中涉及的生物过程密切相关，而外源性化学物质仍可能影响选择的转录组/表观基因组过程。这项研究是将系统暴露与系统生物学相结合以更好地了解化学品与疾病关系的示范。
Environmental health research has recently undergone a dramatic shift, with ongoing technological advancements allowing for broader coverage of exposure and molecular biology signatures. Approaches to integrate such measures are still needed to increase understanding between systems-level exposure and biology. We address this gap by evaluating placental tissues to identify novel chemical-biological interactions associated with preeclampsia. This study tests the hypothesis that understudied chemicals are present in the human placenta and associated with preeclampsia-relevant disruptions, including overall case status (preeclamptic vs. normotensive patients) and underlying transcriptomic/epigenomic signatures. A non-targeted analysis based on high-resolution mass spectrometry was used to analyze placental tissues from a cohort of 35 patients with preeclampsia (n = 18) and normotensive (n = 17) pregnancies. Molecular feature data were prioritized for confirmation based on association with preeclampsia case status and confidence of chemical identification. All molecular features were evaluated for relationships to mRNA, microRNA, and CpG methylation (i.e., multi-omic) signature alterations involved in preeclampsia. A total of 183 molecular features were identified with significantly differentiated abundance in placental extracts of preeclamptic patients; these features clustered into distinct chemical groupings using unsupervised methods. Of these features, 53 were identified (mapping to 40 distinct chemicals) using chemical standards, fragmentation spectra, and chemical metadata. In general, human metabolites had the largest feature intensities and strongest associations with preeclampsia-relevant multi-omic changes. Exogenous drugs were second most abundant and had fewer associations with multi-omic changes. Other exogenous chemicals (non-drugs) were least abundant and had the fewest associations with multi-omic changes. These global data trends suggest that human metabolites are heavily intertwined with biological processes involved in preeclampsia etiology, while exogenous chemicals may still impact select transcriptomic/epigenomic processes. This study serves as a demonstration of merging systems exposures with systems biology to better understand chemical-disease relationships.
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DOI：
10.1016/j.fct.2016.06.023
发表时间：
2016-12
期刊：
Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association
影响因子：
--
作者：
Brooks SA;Martin E;Smeester L;Grace MR;Boggess K;Fry RC
通讯作者：
Fry RC
DOI：
10.1021/jasms.1c00032
发表时间：
2021-05-24
影响因子：
3.2
作者：
Aalizadeh, Reza;Panara, Anthi;Thomaidis, Nikolaos S.
通讯作者：
Thomaidis, Nikolaos S.
影响因子：
3.5
作者：
ANDREWS, KW;SAVITZ, DA;HERTZPICCIOTTO, I
通讯作者：
HERTZPICCIOTTO, I
影响因子：
5.7
作者：
Bright, Harold D.;Howe, Laura D.;O'Keeffe, Linda M.
通讯作者：
O'Keeffe, Linda M.
影响因子：
--
作者：
Dionisio, Kathie L.;Frame, Alicia M.;Judson, Richard S.
通讯作者：
Judson, Richard S.