Summary of Study ST002067

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 PR001309. The data can be accessed directly via it's Project DOI: 10.21228/M8HH60 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	ST002067
Study Title	Time-Resolved Metabolomics of a Mouse Model of Ovarian High-Grade Serous Carcinoma (LC-MS)
Study Summary	The dismally-low survival rate of ovarian cancer patients diagnosed with high-grade serous carcinoma (HGSC) emphasizes the lack of effective screening strategies. One major obstacle is the limited knowledge of the underlying mechanisms of HGSC pathogenesis at very early stages. Here, we present the first 10-month time-resolved serum metabolic profile of a triple mutant (TKO) HGSC mouse model, along with the spatial lipidome profile of its entire reproductive system. A high-coverage liquid chromatography mass spectrometry-based metabolomics approach was applied to longitudinally-collected serum samples from both TKO and TKO control mice, tracking metabolome and lipidome changes from disease onset until death. Spatial lipid distributions within the reproductive system were also mapped via ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, and compared with serum lipid profiles for various lipid classes. Altogether, our results show that the remodeling of lipid and fatty acid metabolism, amino acid biosynthesis, TCA cycle and ovarian steroidogenesis are critical components of HGSC onset and development. These metabolic alterations are accompanied by changes in energy metabolism, mitochondrial and peroxisomal function, redox homeostasis, and inflammatory response, collectively supporting tumorigenesis.
Institute	Georgia Institute of Technology
Last Name	Sah
First Name	Samyukta
Address	901 Atlantic Dr NE, Atlanta, GA, 30332, USA
Email	ssah9@gatech.edu
Phone	574-678-0124
Submit Date	2022-01-26
Raw Data Available	Yes
Raw Data File Type(s)	raw(Thermo)
Analysis Type Detail	LC-MS
Release Date	2022-02-14
Release Version	1

Select appropriate tab below to view additional metadata details:

Project:

Project ID:	PR001309
Project DOI:	doi: 10.21228/M8HH60
Project Title:	Time-Resolved Metabolomics of a Mouse Model of Ovarian High-Grade Serous Carcinoma .
Project Type:	Untargeted serum metabolomics and mass spectrometry imaging
Project Summary:	The dismally-low survival rate of ovarian cancer patients diagnosed with high-grade serous carcinoma (HGSC) emphasizes the lack of effective screening strategies. One major obstacle is the limited knowledge of the underlying mechanisms of HGSC pathogenesis at very early stages. Here, we present the first 10-month time-resolved serum metabolic profile of a triple mutant (TKO) HGSC mouse model, along with the spatial lipidome profile of its entire reproductive system. A high-coverage liquid chromatography mass spectrometry-based metabolomics approach was applied to longitudinally-collected serum samples from both TKO and TKO control mice, tracking metabolome and lipidome changes from disease onset until death. Spatial lipid distributions within the reproductive system were also mapped via ultrahigh-resolution matrix-assisted laser desorption/ionization (MALDI) mass spectrometry, and compared with serum lipid profiles for various lipid classes. Altogether, our results show that the remodeling of lipid and fatty acid metabolism, amino acid biosynthesis, TCA cycle and ovarian steroidogenesis are critical components of HGSC onset and development. These metabolic alterations are accompanied by changes in energy metabolism, mitochondrial and peroxisomal function, redox homeostasis, and inflammatory response, collectively supporting tumorigenesis.
Institute:	Georgia Institute of Technology
Department:	Chemistry and Biochemistry
Last Name:	Sah
First Name:	Samyukta
Address:	901 Atlantic Dr NE, Atlanta, GA, 30332, USA
Email:	ssah9@gatech.edu
Phone:	574-678-0124

Subject:

Subject ID:	SU002149
Subject Type:	Mammal
Subject Species:	Mus musculus
Taxonomy ID:	10090
Gender:	Female

Factors:

Subject type: Mammal; Subject species: Mus musculus (Factor headings shown in green)

mb_sample_id	local_sample_id	Factor
SA194300	-	-
SA194301	C12_1	Control
SA194302	C7_14	Control
SA194303	C7_12	Control
SA194304	C12_2	Control
SA194305	C7_13	Control
SA194306	C12_4	Control
SA194307	C12_7	Control
SA194308	C12_6	Control
SA194309	C12_5	Control
SA194310	C7_11	Control
SA194311	C12_3	Control
SA194312	C7_9	Control
SA194313	C7_4	Control
SA194314	C7_3	Control
SA194315	C7_2	Control
SA194316	C7_1	Control
SA194317	C7_5	Control
SA194318	C7_6	Control
SA194319	C12_8	Control
SA194320	C7_8	Control
SA194321	C7_7	Control
SA194322	C7_10	Control
SA194323	C12_10	Control
SA194324	C8_12	Control
SA194325	C8_11	Control
SA194326	C8_10	Control
SA194327	C8_9	Control
SA194328	C8_13	Control
SA194329	C8_14	Control
SA194330	C9_3	Control
SA194331	C9_2	Control
SA194332	C9_1	Control
SA194333	C8_8	Control
SA194334	C8_7	Control
SA194335	C8_1	Control
SA194336	C12_12	Control
SA194337	C12_11	Control
SA194338	C6_11	Control
SA194339	C8_2	Control
SA194340	C8_3	Control
SA194341	C8_6	Control
SA194342	C8_5	Control
SA194343	C8_4	Control
SA194344	C12_9	Control
SA194345	C6_9	Control
SA194346	C4_14	Control
SA194347	C4_13	Control
SA194348	C4_12	Control
SA194349	C4_11	Control
SA194350	C4_15	Control
SA194351	C4_16	Control
SA194352	C5_3	Control
SA194353	C5_2	Control
SA194354	C5_1	Control
SA194355	C4_10	Control
SA194356	C4_9	Control
SA194357	C4_3	Control
SA194358	C4_2	Control
SA194359	C4_1	Control
SA194360	C3_9	Control
SA194361	C4_4	Control
SA194362	C4_5	Control
SA194363	C4_8	Control
SA194364	C4_7	Control
SA194365	C4_6	Control
SA194366	C5_4	Control
SA194367	C5_5	Control
SA194368	C6_4	Control
SA194369	C6_3	Control
SA194370	C6_2	Control
SA194371	C6_1	Control
SA194372	C6_5	Control
SA194373	C6_6	Control
SA194374	C9_4	Control
SA194375	C6_8	Control
SA194376	C6_7	Control
SA194377	C5_16	Control
SA194378	C5_15	Control
SA194379	C5_9	Control
SA194380	C5_8	Control
SA194381	C5_7	Control
SA194382	C5_6	Control
SA194383	C5_10	Control
SA194384	C5_11	Control
SA194385	C5_14	Control
SA194386	C5_13	Control
SA194387	C5_12	Control
SA194388	C6_10	Control
SA194389	C9_6	Control
SA194390	C14_10	Control
SA194391	C14_9	Control
SA194392	C14_8	Control
SA194393	C14_7	Control
SA194394	C14_11	Control
SA194395	C14_12	Control
SA194396	C15_2	Control
SA194397	C15_1	Control
SA194398	C14_13	Control
SA194399	C14_6	Control

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Collection:

Collection ID:	CO002142
Collection Summary:	Blood samples were collected from 17 TKO mice and 16 TKO control mice starting at 8 weeks of age. A sequential blood sampling procedure was conducted and samples from each mouse were collected every two weeks until end point or ascites. Two TKO mice died after 14 and 16 weeks, and were not included in the UHPLC-MS analysis. One TKO control mouse died after 10 weeks and was also excluded.
Sample Type:	Blood (serum)

Treatment:

Treatment ID:	TR002161
Treatment Summary:	p53LSL R172H/+ Dicer1flox/flox Ptenflox/flox Amhr2cre/+ mice were generated by mating p53LSL-R172H/+Dicer1flox/floxPtenflox/flox female mice with Dicer1flox/floxPtenflox/floxAmhr2cre/+ male mice. p53LSL-R172H/+Dicer1flox/floxPtenflox/flox mice were used as TKO controls (ctrl). TKO ctrl mice carry the same genetic background as TKO mice but do not develop HGSC. p53LSL R172H/+ Dicer1flox/flox Ptenflox/flox Amhr2cre/+ mice were sacrificed in accordance to the animal protocol approved by the institutional animal care and use committee (IACUC) at Indiana University.

Treatment ID:

TR002161

Treatment Summary:

p53LSL R172H/+ Dicer1flox/flox Ptenflox/flox Amhr2cre/+ mice were generated by mating p53LSL-R172H/+Dicer1flox/floxPtenflox/flox female mice with Dicer1flox/floxPtenflox/floxAmhr2cre/+ male mice. p53LSL-R172H/+Dicer1flox/floxPtenflox/flox mice were used as TKO controls (ctrl). TKO ctrl mice carry the same genetic background as TKO mice but do not develop HGSC. p53LSL R172H/+ Dicer1flox/flox Ptenflox/flox Amhr2cre/+ mice were sacrificed in accordance to the animal protocol approved by the institutional animal care and use committee (IACUC) at Indiana University.

Sample Preparation:

Sampleprep ID:	SP002155
Sampleprep Summary:	Serum samples were thawed on ice, followed by metabolite extraction of both non-polar (lipid) and polar metabolites using two different sample preparation protocols. The extraction solvent for RP UHPLC-MS was prepared by adding the isotopically labeled lipid standard mixture to 2-propanol in a 1:60 ratio. Likewise, for HILIC UHPLC-MS, the extraction solvent was prepared by mixing an isotopically labeled mixture of polar metabolites and methanol in a 1:60 ratio. These extraction solvents were added to serum samples in a 3:1 ratio to precipitate proteins. Following this step, samples were vortex-mixed for 30 seconds and centrifuged at 13,000 rpm for 7 minutes. The resulting supernatant was transferred to snap-on LC vials and stored at -80 °C until UHPLC-MS analysis, which was performed within a week. A blank sample, prepared with LC-MS grade water, and 2-propanol (or methanol) underwent the same preparation process as the serum samples, and analyzed together simultaneously. A pooled quality control (QC) was prepared by mixing 5-10 μL aliquots of the extract of each serum sample. This pooled sample was analyzed every 10 runs to monitor LC-MS instrument stability and latter correct for any sensitivity drift. Samples were run in a randomized order on consecutive days.

Sampleprep ID:

SP002155

Sampleprep Summary:

Serum samples were thawed on ice, followed by metabolite extraction of both non-polar (lipid) and polar metabolites using two different sample preparation protocols. The extraction solvent for RP UHPLC-MS was prepared by adding the isotopically labeled lipid standard mixture to 2-propanol in a 1:60 ratio. Likewise, for HILIC UHPLC-MS, the extraction solvent was prepared by mixing an isotopically labeled mixture of polar metabolites and methanol in a 1:60 ratio. These extraction solvents were added to serum samples in a 3:1 ratio to precipitate proteins. Following this step, samples were vortex-mixed for 30 seconds and centrifuged at 13,000 rpm for 7 minutes. The resulting supernatant was transferred to snap-on LC vials and stored at -80 °C until UHPLC-MS analysis, which was performed within a week. A blank sample, prepared with LC-MS grade water, and 2-propanol (or methanol) underwent the same preparation process as the serum samples, and analyzed together simultaneously. A pooled quality control (QC) was prepared by mixing 5-10 μL aliquots of the extract of each serum sample. This pooled sample was analyzed every 10 runs to monitor LC-MS instrument stability and latter correct for any sensitivity drift. Samples were run in a randomized order on consecutive days.

Combined analysis:

Analysis ID	AN003367	AN003368	AN003369
Analysis type	MS	MS	MS
Chromatography type	Reversed phase	Reversed phase	HILIC
Chromatography system	Thermo Dionex Ultimate 3000	Thermo Dionex Ultimate 3000	Thermo Dionex Ultimate 3000
Column	Thermo Accucore C30 (150 x 2.1mm,2.6um)	Thermo Accucore C30 (150 x 2.1mm,2.6um)	Waters Acquity BEH Amide (150 x 2.1mm,1.7um)
MS Type	ESI	ESI	ESI
MS instrument type	Orbitrap	Orbitrap	Orbitrap
MS instrument name	Thermo Q Exactive HF hybrid Orbitrap	Thermo Q Exactive HF hybrid Orbitrap	Thermo Orbitrap ID-X Tribrid
Ion Mode	POSITIVE	NEGATIVE	NEGATIVE
Units	chromatographic peak area	chromatographic peak area	chromatographic peak area

Chromatography:

Chromatography ID:	CH002490
Instrument Name:	Thermo Dionex Ultimate 3000
Column Name:	Thermo Accucore C30 (150 x 2.1mm,2.6um)
Solvent A:	40% water/60% acetonitrile; 10 mM ammonium acetate
Solvent B:	90% isopropanol/10% acetonitrile; 0.1% formic acid; 10 mM ammonium acetate
Chromatography Type:	Reversed phase

Chromatography ID:	CH002491
Instrument Name:	Thermo Dionex Ultimate 3000
Column Name:	Waters Acquity BEH Amide (150 x 2.1mm,1.7um)
Solvent A:	80% water/20% acetonitrile; 0.1% formic acid; 10 mM ammonium acetate
Solvent B:	100% acetonitrile; 0.1% formic acid
Chromatography Type:	HILIC

MS:

MS ID:	MS003134
Analysis ID:	AN003367
Instrument Name:	Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Samples were analyzed in positive and negative ion modes for RP chromatography. Spectral features were extracted using Compound Discoverer v3.0.
Ion Mode:	POSITIVE
Capillary Temperature:	275 °C

MS ID:	MS003135
Analysis ID:	AN003368
Instrument Name:	Thermo Q Exactive HF hybrid Orbitrap
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	amples were analyzed in positive and negative ion modes for RP chromatography. Spectral features were extracted using Compound Discoverer v3.0.
Ion Mode:	NEGATIVE
Capillary Temperature:	275 °C

MS ID:	MS003136
Analysis ID:	AN003369
Instrument Name:	Thermo Orbitrap ID-X Tribrid
Instrument Type:	Orbitrap
MS Type:	ESI
MS Comments:	Both negative and positive ion modes datasets were acquired for HILIC UHPLC-MS, but only the negative ion mode dataset was used for further analysis. The positive mode HILIC UHPLC-MS dataset contained a large number of noisy features that made peak area integration impossible and was therefore removed from the analysis. Spectral features were extracted using Compound Discoverer v3.1.
Ion Mode:	NEGATIVE
Capillary Temperature:	275 °C