Summary of Study ST003699

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 PR002296. The data can be accessed directly via it's Project DOI: 10.21228/M8V83J 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	ST003699
Study Title	Perturbed pediatric circulating metabolome in mild and severe dengue disease
Study Summary	Four billion people are at risk of infection with dengue viruses (DENV), and this burden is rapidly increasing due to geographic expansion of the mosquito vector. Infection with any of the four serotypes of DENV can result in a self-limiting but debilitating febrile illness (DF), and some infections progress to severe disease with hemorrhagic manifestations and shock (dengue hemorrhagic fever/dengue shock syndrome [DHF/DSS]). DENV infection drives the metabolic state of host cells for viral benefit and induces a host-immune response with metabolic implications that link to disease. Here, a dynamic metabolic response to DENV infection and disease was measured in 535 pediatric patients from Nicaragua using liquid chromatography-tandem mass spectrometry. Metabolomic analyses revealed profound disruptions of critical biochemical pathways and metabolites within the circulating metabolome, especially in those with more severe manifestations of dengue disease. A biomarker panel of 28 metabolites was utilized to classify DF versus DHF/DSS with high sensitivity and specificity, equating to a balanced accuracy of 96.88%. Structurally confirmed metabolites belonged to biochemical pathways of omega-3 and omega-6 fatty acids, sphingolipids, dipeptides, purines, and tryptophan metabolism. Dipeptides emerged as the most critical molecules for severe disease classification. Additionally, a previously reported trend between serotonin and platelets in DHF patients was expanded upon here, revealing a major depletion of serotonin, but not platelets, in DSS patients. In this study, the perturbed metabolome was used for disease state classification and exploration of the biochemistry of severe dengue disease pathology.
Institute	Colorado State University
Last Name	Soma
First Name	Paul S.
Address	3185 Rampart Rd, Foothills Campus, Fort Collins, CO 80526
Email	paul.soma@colostate.edu
Phone	610-613-6772
Submit Date	2025-01-28
Num Groups	4
Total Subjects	535
Num Males	278
Num Females	257
Raw Data Available	Yes
Raw Data File Type(s)	mzML
Analysis Type Detail	LC-MS
Release Date	2025-09-29
Release Version	1

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Project:

Project ID:	PR002296
Project DOI:	doi: 10.21228/M8V83J
Project Title:	Perturbed pediatric circulating metabolome in mild and severe dengue disease
Project Summary:	Four billion people are at risk of infection with dengue viruses (DENV), and this burden is rapidly increasing due to geographic expansion of the mosquito vector. Infection with any of the four serotypes of DENV can result in a self-limiting but debilitating febrile illness (DF), and some infections progress to severe disease with hemorrhagic manifestations and shock (dengue hemorrhagic fever/dengue shock syndrome [DHF/DSS]). DENV infection drives the metabolic state of host cells for viral benefit and induces a host-immune response with metabolic implications that link to disease. Here, a dynamic metabolic response to DENV infection and disease was measured in 535 pediatric patients from Nicaragua using liquid chromatography-tandem mass spectrometry. Metabolomic analyses revealed profound disruptions of critical biochemical pathways and metabolites within the circulating metabolome, especially in those with more severe manifestations of dengue disease. A biomarker panel of 28 metabolites was utilized to classify DF versus DHF/DSS with high sensitivity and specificity, equating to a balanced accuracy of 96.88%. Structurally confirmed metabolites belonged to biochemical pathways of omega-3 and omega-6 fatty acids, sphingolipids, dipeptides, purines, and tryptophan metabolism. Dipeptides emerged as the most critical molecules for severe disease classification. Additionally, a previously reported trend between serotonin and platelets in DHF patients was expanded upon here, revealing a major depletion of serotonin, but not platelets, in DSS patients. In this study, the perturbed metabolome was used for disease state classification and exploration of the biochemistry of severe dengue disease pathology.
Institute:	Colorado State University
Department:	Microbiology, Immunology, Pathology
Laboratory:	Perera
Last Name:	Soma
First Name:	Paul
Address:	3185 Rampart Rd, Foothills Campus, Fort Collins, CO 80526
Email:	paul.soma@colostate.edu
Phone:	610-613-6772

Subject:

Subject ID:	SU003831
Subject Type:	Human
Subject Species:	Homo sapiens
Taxonomy ID:	9606
Age Or Age Range:	1-15
Gender:	Male and female

Factors:

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

mb_sample_id	local_sample_id	Sample source	Disease_State
SA404706	364_1686_3_P2-D7_4_E3	NA	ND
SA404707	471_127_4_P2-C4_1_B9	Plasma	DF
SA404708	689_18_6_P2-A1_2_I2	Plasma	DF
SA404709	642_22_6_P1-C2_3_B6	Plasma	DF
SA404710	545_48_5_P1-E3_7_F4	Plasma	DF
SA404711	534_51_5_P1-D4_7_A7	Plasma	DF
SA404712	094_636_1_P2-B7_5_G8	Plasma	DF
SA404713	320_155_3_P2-A1_7_C2	Plasma	DF
SA404714	145_768_2_P1-B8_2_C4	Plasma	DF
SA404715	674_92_6_P1-E8_4_F6	Plasma	DF
SA404716	225_873_2_P2-C5_1_H7	Plasma	DF
SA404717	714_185_6_P2-C1_4_C1	Plasma	DHF
SA404718	431_68_4_P1-F1_5_B8	Plasma	DHF
SA404719	695_187_6_P2-A6_2_D4	Plasma	DHF
SA404720	016_204_1_P1-B3_2_C2	Plasma	DHF
SA404721	084_86_1_P2-A8_7_E7	Plasma	DHF
SA404722	687_178_6_P1-F8_2_E5	Plasma	DHF
SA404723	669_31_6_P1-E4_4_G1	Plasma	DHF
SA404724	325_146_3_P2-A5_5_E7	Plasma	DSS
SA404725	189_251_2_P1-F5_2_E2	Plasma	DSS
SA404726	294_343_3_P1-D9_6_H8	Plasma	DSS
SA404727	651_320_6_P1-C8_6_E1	Plasma	DSS
SA404728	293_97_3_P1-D8_4_H5	Plasma	DSS
SA404729	556_311_5_P1-F3_2_H6	Plasma	DSS
SA404730	409_302_4_P1-D2_5_I1	Plasma	DSS
SA404731	134_299_2_P1-A9_6_B6	Plasma	DSS
SA404732	356_132_3_P2-D1_7_A8	Plasma	DSS
SA404733	022_54_1_P1-B7_2_A2	Plasma	DSS
SA404734	460_275_4_P2-B5_6_G1	Plasma	DSS
SA404735	518_120_5_P1-C1_2_D3	Plasma	DSS
SA404736	404_125_4_P1-C7_4_D9	Plasma	DSS
SA404737	463_148_4_P2-B7_3_A2	Plasma	DSS
SA404738	625_1176_6_P1-A7_4_F4	Plasma	ND
SA404739	671_1208_6_P1-E5_4_F5	Plasma	ND
SA404740	372_1210_4_P1-A1_7_A2	Plasma	ND
SA404741	507_1222_5_P1-B2_6_E2	Plasma	ND
SA404742	005_1223_1_P1-A3_7_A1	Plasma	ND
SA404743	581_1226_5_P2-B3_1_G5	Plasma	ND
SA404744	153_1197_2_P1-C6_2_A8	Plasma	ND
SA404745	313_1234_3_P1-F4_3_G3	Plasma	ND
SA404746	427_1235_4_P1-E7_7_D3	Plasma	ND
SA404747	388_1275_4_P1-B4_3_H2	Plasma	ND
SA404748	436_1239_4_P1-F4_6_E5	Plasma	ND
SA404749	125_1268_2_P1-A2_6_A8	Plasma	ND
SA404750	362_1238_3_P2-D5_4_I6	Plasma	ND
SA404751	716_1242_6_P2-C3_5_B5	Plasma	ND
SA404752	724_1257_6_P2-C9_4_G4	Plasma	ND
SA404753	592_1189_5_P2-C2_2_E9	Plasma	ND
SA404754	378_1264_4_P1-A6_6_D9	Plasma	ND
SA404755	206_788_2_P2-A9_4_H4	Plasma	ND
SA404756	582_1683_5_P2-B4_2_B2	Serum	DF
SA404757	131_1681_2_P1-A7_5_I2	Serum	DF
SA404758	025_1608_1_P1-B9_1_F7	Serum	DF
SA404759	683_1610_6_P1-F5_1_H3	Serum	DF
SA404760	183_1670_2_P1-F1_1_F9	Serum	DF
SA404761	233_1669_2_P2-D1_5_C6	Serum	DF
SA404762	140_1614_2_P1-B4_6_F2	Serum	DF
SA404763	310_1616_3_P1-F3_3_G9	Serum	DF
SA404764	014_1637_1_P1-B1_6_E9	Serum	DF
SA404765	127_1620_2_P1-A4_5_G4	Serum	DF
SA404766	577_1623_5_P2-A9_4_A9	Serum	DF
SA404767	270_1654_3_P1-B8_1_B3	Serum	DF
SA404768	315_1625_3_P1-F6_5_D2	Serum	DF
SA404769	177_1641_2_P1-E5_4_H6	Serum	DF
SA404770	284_1626_3_P1-D1_2_D2	Serum	DF
SA404771	374_1628_4_P1-A3_1_F8	Serum	DF
SA404772	694_1640_6_P2-A5_3_G5	Serum	DF
SA404773	462_1639_4_P2-B6_4_E4	Serum	DF
SA404774	593_1630_5_P2-C3_7_H9	Serum	DF
SA404775	604_1607_5_P2-D3_7_E2	Serum	DF
SA404776	003_1634_1_P1-A1_1_E9	Serum	DF
SA404777	235_1667_2_P2-D3_7_A5	Serum	DF
SA404778	286_1580_3_P1-D2_1_G3	Serum	DF
SA404779	178_1605_2_P1-E6_4_G3	Serum	DF
SA404780	167_1554_2_P1-D7_7_F7	Serum	DF
SA404781	459_1512_4_P2-B4_3_B4	Serum	DF
SA404782	612_1513_5_P2-D8_3_F5	Serum	DF
SA404783	375_1516_4_P1-A4_2_F4	Serum	DF
SA404784	442_1518_4_P1-F9_1_C4	Serum	DF
SA404785	635_1521_6_P1-B5_2_G1	Serum	DF
SA404786	391_1532_4_P1-B7_4_H1	Serum	DF
SA404787	331_1533_3_P2-A9_4_C6	Serum	DF
SA404788	146_1536_2_P1-B9_1_D4	Serum	DF
SA404789	544_1540_5_P1-E2_7_D9	Serum	DF
SA404790	406_1543_4_P1-C9_3_A9	Serum	DF
SA404791	559_1545_5_P1-F4_5_I6	Serum	DF
SA404792	180_1546_2_P1-E8_6_E7	Serum	DF
SA404793	538_1550_5_P1-D7_4_B2	Serum	DF
SA404794	352_1556_3_P2-C7_5_H5	Serum	DF
SA404795	430_1603_4_P1-E9_5_C7	Serum	DF
SA404796	596_1557_5_P2-C5_7_F9	Serum	DF
SA404797	169_1559_2_P1-D9_1_F6	Serum	DF
SA404798	703_1560_6_P2-B2_5_H7	Serum	DF
SA404799	663_1562_6_P1-D9_7_C4	Serum	DF
SA404800	150_1574_2_P1-C3_1_A1	Serum	DF
SA404801	465_1575_4_P2-B9_3_D3	Serum	DF
SA404802	201_1586_2_P2-A6_2_C5	Serum	DF
SA404803	727_1587_6_P2-D3_5_E4	Serum	DF
SA404804	079_1590_1_P2-A5_3_E4	Serum	DF
SA404805	412_1591_4_P1-D5_7_H1	Serum	DF

Showing page 1 of 6 Results: 1 2 3 4 5 Next Last Showing results 1 to 100 of 535

Collection:

Collection ID:	CO003824
Collection Summary:	535 samples from 535 individuals were retrospectively obtained from two different well-established studies in Managua, Nicaragua. A set of 122 well-characterized were sourced from the Pediatric Dengue Cohort Study (PDCS). Those who met the case definition of dengue, or undifferentiated febrile illnesses, were worked up for laboratory confirmation using molecular biological, virological, and/or serological methods. Another 413 samples were obtained from patients 1 to 14 years old in the Pediatric Dengue Hospital-based Study (PDHS) who presented at the Hospital Infantil Manuel de Jesús Rivera, the National Pediatric Reference Hospital in Nicaragua with a fever or history of fever for <7 days and one or more of the following signs and symptoms: headache, arthralgia, myalgia, retro-orbital pain, positive tourniquet test, petechiae, or signs of bleeding. Cases were laboratory-confirmed for DENV infection by detection of DENV RNA by RT-PCR, isolation of DENV, seroconversion of DENV-specific IgM antibody titers observed by MAC-ELISA in paired acute- and convalescent-phase samples, and/or seroconversion or a ≥4-fold increase in anti-DENV antibody titer measured using inhibition ELISA (iELISA) in paired acute and convalescent samples. Immune status was determined using iELISA in early convalescent samples (14 or more days post-onset of symptoms); <2,560 was considered primary infection and ≥2,560 was considered secondary infection. Cases were classified by disease severity (DF, DHF, or DSS) using computerized algorithms based on the 1997 WHO schema. Samples that were negative for DENV infection were classified as ND.
Sample Type:	Blood (serum)
Collection Location:	Managua, Nicaragua

Treatment:

Treatment ID:	TR003840
Treatment Summary:	Cases were classified based on the 1997 World Health Organization schema by dengue disease severity: non-severe dengue fever (DF), or the severe manifestations dengue hemorrhagic fever (DHF) and dengue shock syndrome (DSS). Samples that were negative for DENV infection were classified as non-dengue (ND).

Sample Preparation:

Sampleprep ID:	SP003838
Sampleprep Summary:	Twenty microliters of each sample were aliquoted into individual microcentrifuge tubes, and an additional 20 µL of each serum sample were combined to generate the pooled quality control (QC). For metabolite extraction, patient serum and pooled QC samples were randomized. Five microliters of L-tryptophan-d5 (80 ng/mL) heavy-isotope labeled internal standard were added to 20 µL of patient serum (or pooled QC aliquot) in a microcentrifuge tube. To precipitate proteins, 100 µL of cold methanol was added to the serum and samples were incubated for 12 hours at -80 °C. Samples were then centrifuged at 4 °C for 15 min at 18,000 x g to pellet proteins. Supernatant was then transferred to a new microfuge tube and dried under nitrogen. Samples were reconstituted in 25 µL of methanol/water (50/50), let stand at room temperature for 15 minutes, vortexed for 20 seconds and centrifuged to pellet insoluble debris. Sample supernatants were then transferred to autosampler vials fitted with low-volume inserts and immediately submitted for LC-MS analysis. Serum samples were prepared and analyzed in 6 randomized batches. A pooled quality control sample was run after every 5 experimental samples and a solvent blank was run after every 10 samples.

Sampleprep ID:

SP003838

Sampleprep Summary:

Twenty microliters of each sample were aliquoted into individual microcentrifuge tubes, and an additional 20 µL of each serum sample were combined to generate the pooled quality control (QC). For metabolite extraction, patient serum and pooled QC samples were randomized. Five microliters of L-tryptophan-d5 (80 ng/mL) heavy-isotope labeled internal standard were added to 20 µL of patient serum (or pooled QC aliquot) in a microcentrifuge tube. To precipitate proteins, 100 µL of cold methanol was added to the serum and samples were incubated for 12 hours at -80 °C. Samples were then centrifuged at 4 °C for 15 min at 18,000 x g to pellet proteins. Supernatant was then transferred to a new microfuge tube and dried under nitrogen. Samples were reconstituted in 25 µL of methanol/water (50/50), let stand at room temperature for 15 minutes, vortexed for 20 seconds and centrifuged to pellet insoluble debris. Sample supernatants were then transferred to autosampler vials fitted with low-volume inserts and immediately submitted for LC-MS analysis. Serum samples were prepared and analyzed in 6 randomized batches. A pooled quality control sample was run after every 5 experimental samples and a solvent blank was run after every 10 samples.

Chromatography:

Chromatography ID:	CH004610
Instrument Name:	Agilent 1290
Column Name:	Waters XBridge BEH C18 column (2.1x100mm, 2.5 micron)
Column Temperature:	50
Flow Gradient:	The mobile phase composition began at 5% B and held until 0.5 minutes, then from 0.5 to 14 minutes the mobile phase composition was adjusted in a linear fashion to 98% B. From 14.5 to 15 minutes the mobile phase composition was returned to starting gradient conditions of 5% B. From 15 to 19.5 minutes the starting gradient conditions were held to equilibrate the LC column for the subsequent sample injection.
Flow Rate:	0.25 mL/min
Solvent A:	Water + 0.1% Formic Acid
Solvent B:	Acetonitrile + 0.1% Formic Acid
Chromatography Type:	Reversed phase

Analysis:

Analysis ID:	AN006069
Laboratory Name:	Perera lab at Colorado State University
Analysis Type:	MS
Chromatography ID:	CH004610
Has Mz:	1
Has Rt:	1
Rt Units:	Minutes
Results File:	ST003699_AN006069_Results.txt
Units:	chromatographic peak area