Summary of Study ST002151

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR001364. The data can be accessed directly via it's Project DOI: 10.21228/M8DD7D This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

This study contains a large results data set and is not available in the mwTab file. It is only available for download via FTP as data file(s) here.

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Study ID	ST002151
Study Title	Integrative Exposomic, Transcriptomic, Epigenomic Analyses of Human Placental Samples Links Understudied Chemicals to Preeclampsia
Study Summary	Background 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. Objectives 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. Methods 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 queried against chemicals within the U.S. Environmental Protection Agency’s DSSTox database, and 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. Results 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. Conclusions 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.
Institute	EPA
Last Name	Chao
First Name	Alex
Address	109 TW Alexander Drive, Durham, NC 27709, USA
Email	chao.alex@epa.gov
Phone	9195414261
Submit Date	2022-04-22
Raw Data Available	Yes
Raw Data File Type(s)	mzdata.xml, mgf, mzML
Analysis Type Detail	LC-MS
Release Date	2022-05-09
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR001364
Project DOI:	doi: 10.21228/M8DD7D
Project Title:	Placenta NTA studies
Project Summary:	Multi-omics study on placental samples to characterize xenobiotics and epigenomic/transcriptomic changes associated with preeclampsia
Institute:	U.S. EPA
Last Name:	Chao
First Name:	Alex
Address:	109 TW Alexander Dr, Durham, NC 27709, USA
Email:	chao.alex@epa.gov
Phone:	9195414261

Subject:

Subject ID:	SU002237
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606

Factors:

Subject type: Human; Subject species: Homo sapiens (Factor headings shown in green)

mb_sample_id	local_sample_id	Treatment
SA206151	Blank_Negative_MS_UNC_2	blank
SA206152	Blank_Negative_MS_UNC_3	blank
SA206153	Blank_Negative_MS_UNC_1	blank
SA206154	Blank_Positive_MS_UNC_1	blank
SA206155	Blank_Positive_MS_UNC_2	blank
SA206156	Blank_Positive_MS_UNC_3	blank
SA205981	Blank_Negative_3	Blank
SA205982	Method Blank_Negative_1	Blank
SA205983	Method Blank_Negative_2	Blank
SA205984	Blank_Positive_1	Blank
SA205985	Method Blank_Negative_3	Blank
SA205986	Blank_Negative_2	Blank
SA205987	Blank_Negative_1	Blank
SA205988	Blank_Positive_2	Blank
SA205989	Method Blank_Positive_3	Blank
SA205990	Blank_Positive_3	Blank
SA205991	Method Blank_Positive_2	Blank
SA205992	Method Blank_Positive_1	Blank
SA205993	P12_Negative_1	Control
SA205994	P12_Negative_2	Control
SA205995	P11_Negative_3	Control
SA205996	P10_Negative_3	Control
SA205997	P10_Negative_1	Control
SA205998	P10_Negative_2	Control
SA205999	P12_Negative_3	Control
SA206000	P11_Negative_1	Control
SA206001	P11_Negative_2	Control
SA206002	P13_Negative_3	Control
SA206003	P14_Negative_3	Control
SA206004	P15_Negative_1	Control
SA206005	P15_Negative_2	Control
SA206006	P9_Negative_3	Control
SA206007	P14_Negative_2	Control
SA206008	P13_Negative_2	Control
SA206009	P14_Negative_1	Control
SA206010	P13_Negative_1	Control
SA206011	P5_Negative_2	Control
SA206012	P2_Negative_3	Control
SA206013	P3_Negative_1	Control
SA206014	P3_Negative_2	Control
SA206015	P3_Negative_3	Control
SA206016	P2_Negative_2	Control
SA206017	P2_Negative_1	Control
SA206018	P1_Negative_1	Control
SA206019	P1_Negative_2	Control
SA206020	P1_Negative_3	Control
SA206021	P4_Negative_1	Control
SA206022	P4_Negative_2	Control
SA206023	P8_Negative_2	Control
SA206024	P8_Negative_3	Control
SA206025	P9_Negative_1	Control
SA206026	P8_Negative_1	Control
SA206027	P5_Negative_3	Control
SA206028	P4_Negative_3	Control
SA206029	P5_Negative_1	Control
SA206030	P15_Negative_3	Control
SA206031	P9_Negative_2	Control
SA206032	P18_Negative_2	Control
SA206033	P3_Negative_MSMS	Control
SA206034	P4_Negative_MSMS	Control
SA206035	P5_Negative_MSMS	Control
SA206036	P8_Negative_MSMS	Control
SA206037	P2_Negative_MSMS	Control
SA206038	P1_Negative_MSMS	Control
SA206039	P17_Positive_MSMS	Control
SA206040	P18_Positive_MSMS	Control
SA206041	P19_Positive_MSMS	Control
SA206042	P20_Positive_MSMS	Control
SA206043	P9_Negative_MSMS	Control
SA206044	P10_Negative_MSMS	Control
SA206045	P17_Negative_MSMS	Control
SA206046	P18_Negative_MSMS	Control
SA206047	P19_Negative_MSMS	Control
SA206048	P20_Negative_MSMS	Control
SA206049	P15_Negative_MSMS	Control
SA206050	P14_Negative_MSMS	Control
SA206051	P11_Negative_MSMS	Control
SA206052	P12_Negative_MSMS	Control
SA206053	P13_Negative_MSMS	Control
SA206054	P15_Positive_MSMS	Control
SA206055	P14_Positive_MSMS	Control
SA206056	P19_Negative_3	Control
SA206057	P20_Negative_1	Control
SA206058	P20_Negative_2	Control
SA206059	P20_Negative_3	Control
SA206060	P19_Negative_1	Control
SA206061	P18_Negative_3	Control
SA206062	P17_Negative_2	Control
SA206063	P17_Negative_3	Control
SA206064	P18_Negative_1	Control
SA206065	P1_Positive_MSMS	Control
SA206066	P2_Positive_MSMS	Control
SA206067	P10_Positive_MSMS	Control
SA206068	P11_Positive_MSMS	Control
SA206069	P12_Positive_MSMS	Control
SA206070	P13_Positive_MSMS	Control
SA206071	P9_Positive_MSMS	Control
SA206072	P8_Positive_MSMS	Control
SA206073	P3_Positive_MSMS	Control
SA206074	P4_Positive_MSMS	Control

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Collection:

Collection ID:	CO002230
Collection Summary:	Placentas were first processed by collecting samples ~4-6 inches in length and ½ inch in diameter via cross-section punch biopsy, with blinded identifiers to ensure unbiased collection. These samples were stored at -80°C, until further processing on dry ice into individual samples for chemical analyses. Here, sterile scalpels were used to cut samples in half and a ¼ inch slice was removed from the middle and weighed, yielding isolated samples ranging in weight between 0.4 and 0.6 g.
Sample Type:	Placenta

Treatment:

Treatment ID:	TR002249
Treatment Summary:	Placentas were first processed by collecting samples ~4-6 inches in length and ½ inch in diameter via cross-section punch biopsy, with blinded identifiers to ensure unbiased collection. These samples were stored at -80°C, until further processing on dry ice into individual samples for chemical analyses. Here, sterile scalpels were used to cut samples in half and a ¼ inch slice was removed from the middle and weighed, yielding isolated samples ranging in weight between 0.4 and 0.6 g.

Treatment ID:

TR002249

Treatment Summary:

Placentas were first processed by collecting samples ~4-6 inches in length and ½ inch in diameter via cross-section punch biopsy, with blinded identifiers to ensure unbiased collection. These samples were stored at -80°C, until further processing on dry ice into individual samples for chemical analyses. Here, sterile scalpels were used to cut samples in half and a ¼ inch slice was removed from the middle and weighed, yielding isolated samples ranging in weight between 0.4 and 0.6 g.

Sample Preparation:

Sampleprep ID:	SP002243
Sampleprep Summary:	One sample per tissue was used in chemical analyses. Chemicals were separated from tissue via solid-liquid extraction by adding 2 mL of room temperature water:acetonitrile (1:1) per sample. Placenta samples were disrupted and homogenized using a TissueRuptor (Qiagen), vortexed for 5 min, and placed in a centrifuge at 4000 rpm for 5 min. The resulting supernatant was collected, and a second round of solid-liquid extraction was performed using 8 mL acetonitrile with 2% formic acid. Samples were vortexed and centrifuged again, and both supernatants combined yielding a final total volume of 10 mL. Of the 10 mL combined supernatant sample, 3 mL were then run through solid filtration with a Captiva EMR-lipid column (Agilent Technologies). Resulting eluates were placed into liquid chromatography mass spectrometry (LCMS) vials in 1.0 mL aliquots. Remaining supernatant volumes were banked at -80°C. Method blanks were collected in parallel using the same steps without adding tissues. For non-targeted chemical analysis, 20 µL of 1.25 µg/mL tracer solution was added to each 1.0 mL aliquot of post-filtration eluate (for study samples, blanks, and controls) yielding a final concentration of 25 ng/mL per sample. In addition, tracers were added to a single sample in duplicate prior to extraction to evaluate extraction recovery and reproducibility.

Sampleprep ID:

SP002243

Sampleprep Summary:

One sample per tissue was used in chemical analyses. Chemicals were separated from tissue via solid-liquid extraction by adding 2 mL of room temperature water:acetonitrile (1:1) per sample. Placenta samples were disrupted and homogenized using a TissueRuptor (Qiagen), vortexed for 5 min, and placed in a centrifuge at 4000 rpm for 5 min. The resulting supernatant was collected, and a second round of solid-liquid extraction was performed using 8 mL acetonitrile with 2% formic acid. Samples were vortexed and centrifuged again, and both supernatants combined yielding a final total volume of 10 mL. Of the 10 mL combined supernatant sample, 3 mL were then run through solid filtration with a Captiva EMR-lipid column (Agilent Technologies). Resulting eluates were placed into liquid chromatography mass spectrometry (LCMS) vials in 1.0 mL aliquots. Remaining supernatant volumes were banked at -80°C. Method blanks were collected in parallel using the same steps without adding tissues. For non-targeted chemical analysis, 20 µL of 1.25 µg/mL tracer solution was added to each 1.0 mL aliquot of post-filtration eluate (for study samples, blanks, and controls) yielding a final concentration of 25 ng/mL per sample. In addition, tracers were added to a single sample in duplicate prior to extraction to evaluate extraction recovery and reproducibility.

Combined analysis:

Analysis ID	AN003522
Analysis type	MS
Chromatography type	Reversed phase
Chromatography system	Agilent 1290 Infinity II
Column	Agilent Zorbax Eclipse Plus C8 (150 x 2.1mm,1.8 um)
MS Type	ESI
MS instrument type	QTOF
MS instrument name	Agilent 6545 QTOF
Ion Mode	UNSPECIFIED
Units	amu

Chromatography:

Chromatography ID:	CH002601
Instrument Name:	Agilent 1290 Infinity II
Column Name:	Agilent Zorbax Eclipse Plus C8 (150 x 2.1mm,1.8 um)
Chromatography Type:	Reversed phase

MS:

MS ID:	MS003280
Analysis ID:	AN003522
Instrument Name:	Agilent 6545 QTOF
Instrument Type:	QTOF
MS Type:	ESI
MS Comments:	See Acquisition_Methods.docx for more comprehensive acquisition parameters
Ion Mode:	UNSPECIFIED