Serum Metabolome and Lipidome Changes in Adult Patients with Primary Dengue Infection

10.1371/journal.pntd.0002373PLoS Neglected Tropical Diseases78

Major altered lipid and energy metabolic pathways in dengue patients.

<p>The four points on each line represent the levels of each metabolite at control, Visit 1, Visit 2 and Visit 3, respectively. Differential metabolites colored in red or green represent elevated or decreased change trend at acute stages (within 1 week) after dengue virus infection compared with healthy control subjects. These changes are reversible and there is no significant difference for most of the differential metabolites between healthy controls and dengue patients at convalescence stage (week 3–4). Black-colored metabolites either indicate similar level in healthy controls and dengue fever patients or are undetectable in this study. PC, phosphatidylcholine; PUFA, polyunsaturated fatty acid; LPC, lysophosphatidylcholine; MG, monoacylglyceride; DG, diacylglyceride; TG, triacylglyceride; SM, sphingomyelin.</p

Serum lipids and blood chemistry describes distinct time points in primary dengue infection.

<p><b>A.</b> Orthogonal partial least-squares discriminant analysis (OPLS-DA) models of median-centred and standard deviation scaled glycerophospholipids and sphingolipids and blood chemistry parameters collected from Visit 1 (1 to 3 days after the onset of fever; febrile phase), Visit 2 (4 to 7 days post fever onset; defervescence phase) and Visit 3 (21 to 27 days post fever onset; convalescence phase). <b>B.</b> OPLS-DA VIP plot showing the association of serum glycerophospholipids and sphingolipids with the blood chemistry parameters. Only parameters of VIP values >1.5 are shown. LYMPH#x10∧3/uL, lymphocyte numbers; LYMPH %, percentage of lymphocytes.</p

PCA (A) and OPLS-DA (B) score plots of dengue fever based on metabolomics data.

<p>The principle component analysis (PCA) and orthogonal partial least-squares discriminant analysis (OPLS-DA) models were constructed using LC-MS/MS metabolomics data from healthy subjects and dengue patients at three Visits.</p

Heat map of identified differential metabolites from both LC-MS/MS and GC-MS analyses.

<p>Each row shows ion intensity for a specific metabolite after mean centering and unit variance scaling of the data. Each column shows the serum metabolic profiles of healthy subjects and dengue patients at three visits. * differential metabolites from GC-MS analysis.</p

Typical change trends based on differential metabolite classes.

<p><b>A.</b> elevated change trend of arachidonic acid (free fatty acid). <b>B.</b> elevated change trend of hexanoylcarnitine (acylcarnitine). <b>C.</b> elevated change trend of glucosylceramide (sphingolipid). <b>D.</b> elevated change trend of cortisol (steroid hormone). <b>E.</b> elevated change trend of inosine (purine). <b>F.</b> elevated change trend of biliverdine (bile pigment). <b>G.</b> decreased change trend of PC 38∶8 (phospholipid). <b>H.</b> decreased change trend of tryptophan (amino acid). <b>I.</b> elevated change trend of phenylalanine. Median-horizontal line in the box, The bottom and the top of the box are the 25^th and the 75^th percentiles, and the black band near the middle of the box is the median peak area of the metabolite. * <i>p</i><0.05, ** <i>p</i><0.01, *** <i>p</i><0.001, ns, non-significant by test Kruskal-Wallis test. The statistical comparison was with control levels.</p

Demographics of healthy subjects and dengue patients enrolled in this study.

*<p>Average time from fever to phlebotomy (Visit 1), between Visits 1 & 2 (Visit 2) and between Visits 2 & 3 (Visit-3).</p