Additional file 1 of Identification of kynurenine and quinolinic acid as promising serum biomarkers for drug-induced interstitial lung diseases

Additional file 1: Table S1. Raw data on biomarker concentrations and baseline characteristics of each DILD and DILD recovery sample. # Some samples could not be masured due to insufficient serum available for the quantitative analysis. Table S2. Raw data on biomarker concentrations and baseline characteristics of each serum sample other than DILD. Table S3. Metabolite peak areas measured by HILIC/TOF–MS in DILD serum samples. Table S4. PCR primer pairs used in this study. Table S5. Comparison of serum concentrations of conventional biomarkers among patient groups. Statistical differences between the two groups were examined using the Mann–Whitney U-test with Bonferroni correction. The adjusted p-values are presented in the table. The patients with missing values of the conventional biomarkers were excluded from the statistical analyses. DILD recovery: patients recovered from DILD, DILD-tolerant: the patient group taking similar medications to the DILD group but without DILD onset, BP: bacterial pneumonia, NTM: nontuberculous mycobacteriosis, IIPs: idiopathic interstitial pneumonias, CTD: lung disease associated with connective tissue disease, COPD: chronic obstructive pulmonary disease, BA: bronchial asthma, N.S.: not significant. Table S6. Positive rate of the identified DILD biomarker candidates and conventional biomarkers. The optimal cutoff values of KYN, QUNA, and KYN/TRP were determined using Youden’s index of the ROC curve built between the all-DILD and DILD recovery groups. The positivity rates for other conventional biomarkers were calculated using clinically used cutoff values. The cutoff values for biomarkers are indicated in the parenthesis. Table S7. DILD biomarker potential of tryptophan metabolites compared to serum biomarkers in OP and NSIP patients. AUROC values were calculated from ROC curves, and those with statistical significance (p-value &lt; 0.05) are indicated in bold letters. DILD recovery: patients recovered from DILD, DILD-tolerant: the patient group taking similar medications to the DILD group but without DILD onset, BP: bacterial pneumonia, NTM: nontuberculous mycobacteriosis, IIPs: idiopathic interstitial pneumonias, CTD: lung disease associated with connective tissue disease, COPD: chronic obstructive pulmonary disease, BA: bronchial asthma, HC: healthy control, N.A.: not applicable.附加文件1：表S1。收录了每例药物性间质性肺病（Drug-Induced Interstitial Lung Disease, DILD）及DILD康复样本的生物标志物浓度与基线特征原始数据。# 部分样本因血清量不足以开展定量分析，未能完成检测。表S2。收录了除DILD外其余血清样本的生物标志物浓度与基线特征原始数据。表S3。包含通过亲水作用色谱-飞行时间质谱（Hydrophilic Interaction Chromatography/Time-of-Flight Mass Spectrometry, HILIC/TOF–MS）测得的DILD血清样本代谢物峰面积数据。表S4。列出了本研究使用的聚合酶链式反应（Polymerase Chain Reaction, PCR）引物对序列。表S5。对比了不同患者组的传统生物标志物血清浓度。两组间的统计学差异采用曼-惠特尼U检验（Mann–Whitney U-test）结合邦费罗尼校正（Bonferroni correction）进行分析，校正后的p值已在表中列出。传统生物标志物存在缺失值的患者已被排除在统计分析之外。 DILD康复组：指已康复的DILD患者；DILD耐受组：指服用与DILD组相似药物但未发生DILD的患者群体；BP：细菌性肺炎（Bacterial Pneumonia, BP）；NTM：非结核分枝杆菌病（Nontuberculous Mycobacteriosis, NTM）；IIPs：特发性间质性肺炎（Idiopathic Interstitial Pneumonias, IIPs）；CTD：结缔组织病相关性肺病（Lung Disease Associated with Connective Tissue Disease, CTD）；COPD：慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）；BA：支气管哮喘（Bronchial Asthma, BA）；N.S.：无统计学意义（Not Significant, N.S.）。 表S6。收录了已鉴定的DILD候选生物标志物及传统生物标志物的阳性率。针对犬尿氨酸（Kynurenine, KYN）、喹啉酸（Quinolinic Acid, QUINA）及KYN/TRP比值的最佳截断值，通过构建全DILD组与DILD康复组之间的受试者工作特征曲线（Receiver Operating Characteristic curve, ROC），采用约登指数（Youden’s Index）确定。其余传统生物标志物的阳性率则采用临床常用截断值计算。各生物标志物的截断值已标注于括号内。 表S7。对比了色氨酸代谢产物与其他血清生物标志物在机化性肺炎（Organizing Pneumonia, OP）及非特异性间质性肺炎（Non-Specific Interstitial Pneumonia, NSIP）患者中的DILD诊断潜力。通过ROC曲线计算受试者工作特征曲线下面积（Area Under the Receiver Operating Characteristic Curve, AUROC），其中具有统计学显著性（p值<0.05）的结果已以粗体标注。 DILD康复组：指已康复的DILD患者；DILD耐受组：指服用与DILD组相似药物但未发生DILD的患者群体；BP：细菌性肺炎（Bacterial Pneumonia, BP）；NTM：非结核分枝杆菌病（Nontuberculous Mycobacteriosis, NTM）；IIPs：特发性间质性肺炎（Idiopathic Interstitial Pneumonias, IIPs）；CTD：结缔组织病相关性肺病（Lung Disease Associated with Connective Tissue Disease, CTD）；COPD：慢性阻塞性肺疾病（Chronic Obstructive Pulmonary Disease, COPD）；BA：支气管哮喘（Bronchial Asthma, BA）；HC：健康对照（Healthy Control, HC）；N.A.：不适用（Not Applicable, N.A.）。