Integrated analysis of WGCNA and machine learning identified diagnostic biomarkers in trauma-induced coagulopathy.

Journal: Scientific reports
Published Date:

Abstract

Despite advancements in trauma care, uncontrolled hemorrhage and trauma-induced coagulopathy (TIC) remain the leading causes of preventable deaths after trauma. Understanding the genetic underpinnings and molecular mechanisms of TIC is crucial for developing effective diagnostic and therapeutic strategies. This study employed a comprehensive bioinformatics approach to elucidate the genetic landscape associated with TIC. Gene expression data from 20 samples, comprising 10 controls and 10 severe trauma patients with TIC, were analyzed. This approach included principal component analysis, differential gene expression analysis using DESeq2, Gene Set Enrichment Analysis (GSEA), weighted gene co-expression network analysis (WGCNA), and machine learning (ML) algorithms (support vector machine-recursive feature elimination, least absolute shrinkage and selection operator, and random forest) for feature gene identification. Functional analysis of genes and immunoinfiltration analysis were also conducted. A total of 1014 differentially expressed genes (DEGs) were identified, indicating significant genetic alterations in TIC. GSEA confirmed the involvement of critical pathways, and WGCNA identified 35 relevant gene modules. The integration of ML algorithms highlighted nine key feature genes (TFPI, MMP9, ABCG5, TPSAB1, TK1, IGKV3D.11, SAMSN1, TIMP3, and GZMB). Immunoinfiltration analysis revealed distinct immune cell compositions in TIC samples. The multifactor regulation network provided insights into complex gene regulatory mechanisms. This study presents a detailed genetic and molecular profile of TIC. Integrating various bioinformatics tools and ML algorithms has enabled the identification of potential biomarkers and therapeutic targets. These findings could significantly contribute to improving the diagnostic accuracy and treatment efficacy for patients with TIC, potentially reducing the mortality rates associated with trauma.

Authors

  • Qingsong Chen
    Guangdong Provincial Engineering Technology Research Center of Public Health Detection and Assessment, School of Public Health, Guangdong Pharmaceutical University, Guangzhou, 510310, PR China. Electronic address: qingsongchen@aliyun.com.
  • Tao Li
    Department of Emergency Medicine, Jining No.1 People's Hospital, Jining, China.
  • Tao Zhang
    Department of Traumatology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, School of Medicine, Chongqing University, Chongqing, 40044, People's Republic of China.
  • Yue Zhou
    State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, 2A Nanwei Road, Beijing 100050, China. zhouyue@imm.ac.cn.
  • Weifeng Huang
    School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou 510006, China.
  • Hui Li
    Department of Ophthalmology, Beijing Hospital, National Center of Gerontology, Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, Beijing, China.
  • Li Shi
    Department of Integrated Chinese and Western Medicine, Second Xiangya Hospital, Central South University, Changsha 410011, China.
  • Jianxiao Li
    Department of the Traumatology, Chongqing Emergency Medical Center, National Regional Tramadol Center, Chongqing University Central Hospital, Chongqing, China.
  • Qi Zhang
    Department of Gastroenterology, The Affiliated Hospital of Qingdao University, Qingdao, China.
  • Man Ma
    Department of the Traumatology, Chongqing Emergency Medical Center, National Regional Tramadol Center, Chongqing University Central Hospital, Chongqing, China.
  • Pan Wang
  • Hui Hu
    Department of Epidemiology, College of Medicine & College of Public Health and Health Professions, University of Florida, Gainesville, FL, USA.
  • Gongbin Wei
    Department of the Traumatology, Chongqing Emergency Medical Center, National Regional Tramadol Center, Chongqing University Central Hospital, Chongqing, China.
  • Jiangxia Xiang
    Department of the Traumatology, Chongqing Emergency Medical Center, National Regional Tramadol Center, Chongqing University Central Hospital, Chongqing, China.
  • Yuan Cheng
    Science Island Branch, University of Science and Technology of China, Hefei, Anhui, China.
  • Jun Yang
    Cardiovascular Endocrinology Laboratory, Hudson Institute of Medical Research, Clayton, Victoria, Australia; Department of Medicine, Monash University, Clayton, Victoria, Australia.
  • Guangbin Huang
    Department of Traumatology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, 40014, People's Republic of China.
  • Yongming Li
    State Key Laboratory of Respiratory Disease, National Clinical Research Center for Respiratory Disease, Guangzhou Institute of Respiratory Health, The First Affiliated Hospital of Guangzhou Medical University, National Center for Respiratory Medicine, Guangzhou, China.
  • Dingyuan Du
    Department of Traumatology, Chongqing Emergency Medical Center, Chongqing University Central Hospital, Chongqing, 40014, People's Republic of China.