Deconvolution of bulk RNA sequencing in activated phosphoinositide 3-kinase syndrome

Background: Many gaps remain in our understanding of the immune and molecular characteristics that underlie activated phosphoinositide 3-kinase delta syndrome (APDS). Methods: We performed RNA sequencing of peripheral blood leukocytes obtained from a child with APDS and his healthy parents and deconvoluted bulk transcriptional data to assess immune cell status. Results: Pathway enrichment analysis suggested signaling pathways enriched in virus infection as well as the PI3K, mitogen-activated protein kinase (MAPK), natural killer cell-mediated cytotoxicity, and nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathways. The proportion of B cells memory, T cells CD4 memory resting and dendritic cells activated were reduced, whereas B cells naive, T cells CD8, NK cells resting, monocytes and macrophages M2 were increased in the child. Top 10 hub genes were screened and showed moderate to strong relatedness with immune cell proportions. Conclusion: Deconvolution of bulk RNA sequencing to assess immune cells status can provide further insight into the alterations in immunological features underlying APDS and other rare diseases.