School of Computer Science and Engineering, Kyungpook National University, Daegu, 41566, Republic of Korea.
Kyungpook National University Chilgok Hospital, 807 Hoguk-ro, Buk-gu, Daegu, 41404, Republic of Korea.
Sci Rep. 2024 Oct 21;14(1):24712. doi: 10.1038/s41598-024-75924-x.
Understanding the immune response to COVID-19 is challenging due to its high variability among individuals. To identify differentially expressed cytokines between the deteriorating and recovering phases, we analyzed the Electronic Health Records (EHR) and cytokine profile data in a COVID-19 cohort of 444 infected patients and 145 non-infected healthy individuals. We categorized each patient's progression into Deterioration Phase (DP) and Recovery Phase (RP) using longitudinal neutrophil, lymphocyte and lactate dehydrogenase levels. A random forest model was built using healthy and severe patients to compute the contribution of each cytokine toward disease progression using Shapley Additive Explanations (SHAP). SHAP values were used for supervised clustering to identify DP and RP-related samples and their associated cytokines. The identified clusters effectively discriminated DP and RP samples, suggesting that the cytokine profiles differed between deteriorating and recovering health conditions. Especially, CXCL10, GDF15, PTX3, and TNFSF10 were differentially expressed between the DP and RP samples, which are involved in the JAK-STAT, NF- B, and MAPK signaling pathways contributing to the inflammatory response. Collectively, we characterized the immune response in terms of disease progression of COVID-19 with deteriorating and recovering health conditions.
由于个体之间的高度变异性，了解 COVID-19 的免疫反应具有挑战性。为了鉴定出在恶化和恢复阶段之间差异表达的细胞因子，我们分析了 444 名感染患者和 145 名非感染健康个体的电子健康记录（EHR）和细胞因子谱数据。我们使用纵向中性粒细胞、淋巴细胞和乳酸脱氢酶水平，将每个患者的进展分为恶化期（DP）和恢复期（RP）。使用健康和重症患者构建随机森林模型，使用 Shapley 加法解释（SHAP）计算每个细胞因子对疾病进展的贡献。使用 SHAP 值进行监督聚类，以鉴定 DP 和 RP 相关的样本及其相关细胞因子。鉴定出的聚类有效地区分了 DP 和 RP 样本，表明在恶化和恢复健康状况之间细胞因子谱存在差异。特别是，DP 和 RP 样本之间差异表达的细胞因子包括 CXCL10、GDF15、PTX3 和 TNFSF10，它们参与 JAK-STAT、NF-κB 和 MAPK 信号通路，促进炎症反应。总之，我们根据 COVID-19 恶化和恢复健康状况的疾病进展来描述免疫反应。
