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. 2021 Dec 1;11:23194. doi: 10.1038/s41598-021-02679-0

Table 2.

Metabolites significantly increased with increased Procalcitonin over days 0–7.

Metabolite β coefficient metabolite p-value − log10p q-value Super pathway Sub pathway
3-Hydroxybutyrylcarnitine (C3-DC) 4.17 1.19 E−04 3.92 6.78 E−04 Lipid Short-chain acylcarnitine
Succinylcarnitine (C4) 4.22 7.58 E−04 3.12 3.17 E−03 Energy Short-chain acylcarnitine
Tiglyl carnitine (C5) 4.42 9.86 E−05 4.01 5.89 E−04 Amino acid Short-chain acylcarnitine
2-Methylbutyroylcarnitine (C5) 3.73 4.04 E−04 3.39 1.86 E−03 Amino acid Short-chain acylcarnitine
Adipoylcarnitine (C6-DC) 4.42 1.50 E−05 4.82 1.20 E−04 Lipid Short-chain acylcarnitine
3-Methyladipoylcarnitine (C7-DC) 3.08 4.32 E−03 2.36 1.45 E−02 Lipid Short-chain acylcarnitine
Octanoylcarnitine (C8) 4.09 3.83 E−04 3.42 1.79 E−03 Lipid Medium-chain acylcarnitine
Suberoylcarnitine (C8-DC) 3.19 5.57 E–−04 3.25 2.45 E−03 Lipid Medium-chain acylcarnitine
cis-4-Decenoylcarnitine (C10:1) 4.12 7.12 E−04 3.15 2.99 E−03 Lipid Medium-chain acylcarnitine
Decanoylcarnitine (C10) 3.94 6.74 E−04 3.17 2.86 E−03 Lipid Medium-chain Acylcarnitine
3-Methyladipate 5.74 7.40 E−09 8.13 1.91 E−07 Lipid Fatty acid, dicarboxylate
Adipate 3.00 4.31 E−03 2.37 1.45 E−02 Lipid Fatty acid, dicarboxylate
3-Hydroxyadipatea 2.91 1.89 E−03 2.72 7.03 E−03 Lipid Fatty acid, dicarboxylate
2-Hydroxyadipate 2.77 3.30 E−03 2.48 1.15 E−02 Lipid Fatty acid, dicarboxylate
heptenedioate (C7:1-DC)a 3.08 1.83 E−03 2.74 6.83 E−03 Lipid Fatty acid, dicarboxylate
Suberate (C8-DC) 4.26 9.47 E−05 4.02 5.80 E−04 Lipid Fatty acid, dicarboxylate
Dodecanedioate (C12) 3.41 3.01 E−04 3.52 1.46 E–03 Lipid Fatty acid, dicarboxylate
Dodecenedioate (C12:1-DC)a 2.69 4.47 E−03 2.35 1.50 E−02 Lipid Fatty acid, dicarboxylate
Hexadecanedioate (C16) 3.43 2.75 E−04 3.56 1.35 E−03 Lipid Fatty acid, dicarboxylate
Octadecadienedioate (C18:2-DC)a 3.81 2.86 E−04 3.54 1.40 E−03 Lipid Fatty acid, dicarboxylate
Octadecenedioate (C18:1-DC)a 3.09 1.50 E−03 2.83 5.82 E−03 Lipid Fatty acid, dicarboxylate
Octadecanedioate (C18) 2.51 7.54 E−03 2.12 2.32 E−02 Lipid Fatty acid, dicarboxylate
Eicosanodioate (C20-DC) 4.77 6.57 E−04 3.18 2.80 E−03 Lipid Fatty acid, dicarboxylate
Methylsuccinate 7.44 1.87 E−10 9.73 8.31 E−09 Amino acid BCAA metabolism
3-Methylglutaconate 6.46 7.79 E−09 8.11 1.96 E−07 Amino acid BCAA metabolism
2,3-Dihydroxy-2-methylbutyrate 6.44 2.75 E−09 8.56 8.70 E−08 Amino acid BCAA metabolism
3-Hydroxy-2-ethylpropionate 5.22 1.64 E−04 3.79 8.72 E−04 Amino acid BCAA metabolism
N-Acetylvaline 5.19 6.79 E−04 3.17 2.87 E−03 Amino acid BCAA metabolism
beta-Hydroxyisovalerate 5.16 1.30 E−04 3.89 7.20 E−04 Amino acid BCAA metabolism
N-Acetylisoleucine 4.25 2.35 E−03 2.63 8.50 E−03 Amino acid BCAA metabolism
Ethylmalonate 4.16 1.29 E−03 2.89 5.21 E−03 Amino acid BCAA metabolism
Isovalerylglycine 2.29 1.52 E−02 1.82 4.08 E−02 Amino acid BCAA metabolism
Sedoheptulose 4.78 2.40 E−05 4.62 1.83 E−04 Carbohydrate Pentose metabolism
Arabonate/xylonate 4.37 5.22 E−04 3.28 2.35 E−03 Carbohydrate Pentose metabolism
Ribonate 3.98 3.03 E−03 2.52 1.07 E−02 Carbohydrate Pentose metabolism
Arabinose 3.60 1.31 E−03 2.88 5.26 E−03 Carbohydrate Pentose metabolism
Ribitol 3.26 1.30 E−02 1.89 3.61 E−02 Carbohydrate Pentose metabolism

Using repeated measures data (day 0, 3 and 7), the association between relative quantitation of each individual metabolite noted above and Procalcitonin levels over time were determined utilizing linear mixed-effects models correcting for age, sex, baseline 25(OH)D, absolute increase in 25(OH)D, SAPS II, admission diagnosis, plasma day and an individual subject-specific random-intercept. All significant mixed-effects associations have false discovery rate adjusted p-value (q-value) < 0.05. BCAA is Branched-Chain Amino Acids inclusive of Leucine, Isoleucine and Valine. For the Acylcarnitines sub pathway: a capital C is followed by the number of carbons within the fatty acyl group attached to the carnitine. A colon followed by a number is one or more unsaturated carbons in the acylcarnitine ester (i.e. C10:1 is a monounsaturated C10 acylcarnitine). DC following the carbon number is a dicarboxylic acylcarnitine.

aPutative identification (Level 2) where predictive or externally acquired structure evidence is present when a reference standard does not exist.