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

Gustavo Sganzerla MartinezAlexis GardunoAli Toloue OstadgavahiBenjamin HewinsMansi DuttAnuj KumarIgnacio Martín-LoechesDavid J Kelvin
Published in: International journal of molecular sciences (2024)
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 CD3 , CD14 , CD16 , FOSB , S100A12 , and TCRɣδ 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.
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