eFigure 1.Analytic steps for metabolomic profiles.Total N refers to sample size of patients, m refers to metabolites.

eFigure 2. Scatter plot of relative pseudouridine levels in mouse kidney and liver homogenates at 8 hrs after cecal ligation and puncture. Horizontal bar corresponds to group means.

eTable 1. Examples of significant metabolites between non-survivors (cases) and survivors (controls) of pneumonia and sepsis at 90 days. Metabolites shown if 0.01< p value ≤ 0.05 and q value<0.1.

Super pathway / Sub pathway / Metabolite / Relative abundance*
Cases / Controls / P value
Amino acids / Alanine / N-acetyl-beta-alanine / 1.06 (0.83, 2.01) / 0.86 (0.67,1.13) / 0.018
Cysteine / S-methylcysteine / 0.64 (0.53, 1.02) / 1.14 (0.99, 1.53) / 0.015
Threonine / N-acetylthreonine / 1.58 (1.08, 2.34) / 1.14 (0.99, 1.53) / 0.012
Guanidino and acetamido / 4-acetamidobutanoate / 1.73 (0.79, 2.20) / 0.75 (0.56, 01.06) / 0.018
Phenylalanine / N-acetylphenylalanine / 1.12 (0.97, 2.23) / 0.80 (0.60, 1.32) / 0.012
Carbo-hydrate / Sucrose metabolism / sucrose / 1.08 (0.76, 3.04) / 0.52 (0.28, 1.09) / 0.012
Nucleotide sugar / arabitol / 1.38 (0.90, 2.04) / 0.84 (0.67, 1.00) / 0.015
threitol / 2.38 (0.76, 3.05) / 0.85 (0.61, 1.32) / 0.012
Lipids / Fatty acid, dicarboxylate / hexadecanedioate / 1.32 (0.80, 2.74) / 0.77 (0.38, 1.08) / 0.018
Lysolipid / 1-linoleoylglycerophos-phocholine / 0.79 (0.44, 1.09) / 1.94 (0.84, 3.27) / 0.018
2-linoleoylglycerophos-phoethanolamine* / 0.65 (0.32, 1.01) / 1.12 (0.94, 2.14) / 0.013
1-arachidonoylglycero-phosphoethanolamine* / 0.68 (0.43, 1.45) / 1.72 (0.92, 2.44) / 0.018
Steroid metabolism / 5alpha-pregnan-3alpha,20 beta-dioldisulfate 1* / 1.24 (0.62, 3.08) / 0.28 (0.19, 0.66) / 0.012
Nucleotides / Purine/adenosine metabolism / N2,N2dimethylguanosine / 1.46 (0.91, 2.30) / 0.96 (0.69, 1.03) / 0.015
N6-carbamoylthreonyl-adenosine / 0.66 (0.39, 2.14) / 0.39 (0.39, 0.57) / 0.014
allantoin / 2.28 (0.92, 4.13) / 0.97 (0.78, 1.09) / 0.015

# Metabolites selected for illustration if 0.01 < p value ≤ 0.05 and q value<0.1

* Relative abundance determined as median [IQR] of normalized, imputed raw area counts

^ P values determined using the Wilcoxon signed rank test

eTable 2.Relative abundance of selected metabolites in liver and kidney homogenates comparing CLP mice to sham at eight hours.

Metabolite / Liver homogenate / Kidney homogenate
CLP sepsis / Placebo / P value / Q value / CLP sepsis / Placebo / P value / Q value
pseudouridine / 1.28 [1.0, 1.44] / 0.83 [0.64, 0.90] / 0.026 / 0.047 / 1.38 [0.99, 1.84] / 0.85 [0.81, 1.05] / 0.01 / 0.03
N1-methyl adenosine / 1.28 [0.85,1.34] / 0.74 [0.74, 0.78] / 0.031 / 0.05 / 1.03 [0.87, 1.06] / 1.0 [0.89, 1.06] / 0.26 / 0.24
allantoin / 1.02 [0.94, 1.28] / 1.0 [0.88, 1.04] / 0.47 / 0.28 / 2.25 [1.03,3.85] / 0.90 [0.76, 0.95] / 0.01 / 0.03