Predicting candidate biomarkers for COVID-19 associated with leukemia in children.

Abstract

Since the COVID-19 pandemic, a significant number of pediatric leukemia patients have shown to have also contracted COVID-19 several weeks or months prior to the development of their cancer. Current research indicates the expression of MDA5, encoded by IFIH1, is associated with increased immunity to COVID-19 in children. Children are also known to have a much lower risk of developing leukemia. Our hypothesis is that IFIH1 and its regulatory miRNAs are biomarkers associated with pediatric leukemia; the objective of our study is to identify genes, through miRNA targeting mechanisms, which may be biomarkers associated with COVID-19 infection and leukemia. The database TarBase was analyzed to identify miRNAs that target IFIH1, followed by the identification of other genes regulated by IFIH1's targeting miRNAs, to construct a gene-miRNA targeting network. Protein-Protein Interaction (PPI) analysis and DAVID/KEGG pathway analysis were conducted to identify genes with meaningful biological interactions and pathways. We identified two significant miRNAs, hsa-196a-5p and hsa-196b-5p, and 51 of their targeted and highly expressed genes reported in the Acute Myeloid Leukemia (AML) samples from The Cancer Genome Atlas (TCGA) RNA sequencing database. When conducting additional analysis using the Gene Constellation module of the Immunological Genome Project for the top three candidate genes, several other genes were identified to be highly correlated with STAT3 and IFIH1 in our study. Based on our investigation into co-expression analysis, we found that IFIH1 is a potential biomarker for AML. We are expanding our work to create a machine learning model to identify other biomarkers, examine the significance of various parameters (age, race, etc.), and perform comorbidity network analysis for other potential genes/miRNAs.