The whole blood microbiome of Indonesians reveals that environmental differences shape immune gene expression signatures

Pathogens found within local environments are a major cause of morbidity and mortality. This is particularly true in Indonesia, where infectious diseases such as malaria or dengue are a significant part of the disease burden within the country. One way to strengthen the control of infectious diseases is through better surveillance, however unequal investment in medical funding throughout Indonesia, particularly in rural areas, has resulted in under-reporting of cases. Here, we use transcriptome data from 117 healthy individuals living on the islands of Mentawai, Sumba, and the Indonesian side of New Guinea Island to explore which pathogens are present within whole blood. We are able to detect a broad range of taxa within RNA-sequencing data generated from whole blood, including bacteria, viruses, archaea, and eukaryotes. Using independent component analysis, we find that two of these pathogens—Flaviviridae and Plasmodium—have the most noticeable effects on expression profiles. We also identify specific genes linked with Plasmodium and Flavivirus abundance and find that both of these infections are most pronounced in the easternmost island within our Indonesian dataset. This study provides a framework for novel applications of RNA-seq as surveillance and a better understanding of environmental contributors affecting gene expression within Indonesia. ### Competing Interest Statement The authors have declared no competing interest.