Fig. 1
Identification of potential serum DILD biomarkers using metabolomic analyses for hydrophilic molecules. A Scheme showing unbiased metabolomic analysis (screening cohort) and quantitative analysis (validation cohort) for hydrophilic molecules in serum obtained from patients with DILD and recovered patients. Subsequently, the potential of the identified DILD biomarker candidates was evaluated using the combined cohort of patients with DILD, along with DILD-tolerant patients, patients with other lung diseases, and HC. Patient characteristics are summarized in Table 1, Additional file 1: Tables S1, and S2. B Serum levels of 943 hydrophilic molecules detected in metabolomic analysis were compared between patients with DILD and recovered patients (n = 60 and 34, respectively) in the volcano plot. In the analysis, a very stringent criterion was applied (p-value < 5.30 × 10−5 = 0.05/943; two-tailed Welch’s t-test with Bonferroni correction). Significantly increased or decreased molecules (fold change > 2 or < 0.5, and p-value < 5.30 × 10−5) are colored with red. Molecules not-significantly increased or decreased (fold change > 2 or < 0.5, p-value > 5.30 × 10−5) are colored with green. Only five detected molecules showed significantly increased (p-value < 5.30 × 10−5, fold change > 2) serum levels with high g-value (> 0.8) and high diagnostic potential (area under the ROC curve > 0.8) in acute DILD patients. Those molecules are labeled with tentative metabolite names