Proportions were compared with Fisher’s exact test, and comparisons of continuous variables between groups were performed with a Mann-Whitney U test or Kruskall-Wallis test as appropriate. A p-value < 0.05 was considered significant.
Metabolomic data was normalized based on MSTUS method44 (link) implemented in NOREVA (http://idrb.zju.edu.cn/noreva/)45 (link) prior to statistical analysis. Univariate statistical analysis was conducted based on Mann-Whitney U test using IMB SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, N.Y., USA). For correction for multiple testing, significance analysis of microarray (SAM) was applied to control false discovery rate (FDR). Multivariate statistical analysis was performed for partial least squares-discriminant analysis (PLS-DA) by SIMCA 15 (Umetrics AB, Umea, Sweden). Binary logistic regression analysis with forward selection was conducted using IMB SPSS Statistics for Windows, version 25.0 (IBM Corp., Armonk, N.Y., USA). Receiver operating characteristic (ROC) analysis was performed using MedCalc for Windows, version 12.7.0.0 (MedCalc Software, Ostend, Belgium).
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