Identification of Marker Genes in Infectious Diseases from ScRNA-seq Data Using Interpretable Machine Learning.

Journal: International journal of molecular sciences
PMID:

Abstract

A common result of infection is an abnormal immune response, which may be detrimental to the host. To control the infection, the immune system might undergo regulation, therefore producing an excess of either pro-inflammatory or anti-inflammatory pathways that can lead to widespread inflammation, tissue damage, and organ failure. A dysregulated immune response can manifest as changes in differentiated immune cell populations and concentrations of circulating biomarkers. To propose an early diagnostic system that enables differentiation and identifies the severity of immune-dysregulated syndromes, we built an artificial intelligence tool that uses input data from single-cell RNA sequencing. In our results, single-cell transcriptomics successfully distinguished between mild and severe sepsis and COVID-19 infections. Moreover, by interpreting the decision patterns of our classification system, we identified that different immune cells upregulating or downregulating the expression of the genes , , , , , and can accurately differentiate between different degrees of infection. Our research has identified genes of significance that effectively distinguish between infections, offering promising prospects as diagnostic markers and providing potential targets for therapeutic intervention.

Authors

  • Gustavo Sganzerla Martinez
    Programa de Pós-Graduação em Biotecnologia, Universidade de Caxias do Sul, Caxias do Sul, RS, Brazil.
  • Alexis Garduno
    Department of Clinical Medicine, Trinity College Dublin, D08 NHY1 Dublin, Ireland.
  • Ali Toloue Ostadgavahi
    Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4H7, Canada.
  • Benjamin Hewins
    Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4H7, Canada.
  • Mansi Dutt
    Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4H7, Canada.
  • Anuj Kumar
    Apeejay School of Management, Dwarka, Delhi, India.
  • Ignacio Martin-Loeches
    Department of Intensive Care Medicine, Multidisciplinary Intensive Care Research Organization (MICRO), St James' Hospital, Dublin, Ireland.
  • David J Kelvin
    Microbiology and Immunology, Dalhousie University, Halifax, NS B3H 4H7, Canada.