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I'm very excited to share the results of our new paper, now available on Biorxiv: https://biorxiv.org/cgi/content/short/2021.01.07.425684v1. Below is a thread of the main results https://twitter.com/biorxivpreprint/status/1347627193132851208
This project originated from a previous study analysing diversity amongst three Indonesian populations capturing the main genomic and geographical axes of the country: https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1008749
Within this dataset, four samples were PCR-confirmed to have malaria, a major public health issue in the country. This made us wonder: what does the transcriptome of malaria-infected individuals look like in populations of Indonesian ancestry?
Most studies on the host response to malaria have come from populations of African ancestry, the WHO region with the most malaria cases. However, since host genetics impacts malaria pathogenesis, we wanted to explore how this looks like in Indonesia.
Along with having a very different evolutionary history to previous studies done on the host response to malaria, Indonesia is also unique from most of Africa in that it has two main vectors that transmit malaria: Plasmodium falciparum and Plasmodium vivax.
Four malaria-confirmed samples is quite small, so we also combined our dataset with another published dataset from Yamagishi et al. ( https://pubmed.ncbi.nlm.nih.gov/25091627/ ) , giving us 69 individuals with simple forms of malaria (P. falciparum = 61; P. vivax = 8) and 132 healthy controls
After correcting for technical covariates, we found Indonesian individuals infected with P. falciparum to have an upregulation of genes involved in immediate early response and inflammatory genes, all previously-reported pathways during malaria infection.
For P. vivax, we found similar signals, however there was a much weaker signal in the defense and inflammatory response.
To see how this compares to previously-published studies, we next compared our significantly DE genes with three other global datasets: two from Africa (Mali and Benin) for P. falciparum and two datasets from South America (Colombia) for P. vivax
We found a lot of overlap between the populations, which is promising for biomarkers and therapeutics. We also found that Indonesia has its own unique set of genes and pathways, primarily those involved in RNA splicing and cell surface receptor genes.
We still have a long way to go, but this research sheds some light on how malaria infection affects the human host across a range of genetic backgrounds, an important understanding if we aim to have a broad range of therapeutics that are effective for everyone.
