The Malaria Red Blood Atlas

Malaria remains a global health problem with over 400,000 deaths annually. Plasmodium parasites, the causative agents of malaria, replicate asexually in red blood cells (RBCs) of their vertebrate host, while a subset differentiates into sexual stages (gametocytes) for mosquito transmission. Parasite replication and gametocyte maturation in the erythropoietic niches of the bone marrow and spleen contribute to pathogenesis and drive transmission, but the mechanisms underlying this organ enrichment remain unknown. We performed a comprehensive single cell analysis of rodent P. berghei in spleen, bone marrow and blood to define parasite phenotypes specific to those niches. After quality control, we obtained over 19,000 host single cell transcriptomes from spleen and bone marrow and over 33,000 P. berghei transcriptomes from all three organs, allowing us to investigate host response to infection as well as parasite-specific adaptation to host organ and host cell. Single cell RNA-seq analysis of host and parasite cells revealed an interferon-driven host response to infection as well as transcriptional adaptations of Plasmodium to host organ and RBC maturation status. Our data provides a thorough characterisation of host-parasite interactions in erythropoietic niches and defines host cell maturation state as the key driver of parasite adaptation.

Here, you can explore the parasite transcriptomes in reticulocytes and normocytes as defined by host RNA content. The data set includes the complete asexual replication cycle as well as parasite cells differentiating into male and female sexual transmission forms (gametocytes). The results are displayed in 2 sections

Clustering - Allows cluster visualization and exploration of top cluster markers. Each cluster was annotated as a parasite stage based on comparison with the malaria cell atlas - see: BioRxiv: Host cell maturation modulates parasite invasion and sexual differentiation in Plasmodium

Hentzschel, Franziska; Gibbins, Matthew; Attipa, Charalampos; Beraldi, Dario; Moxon, Chris; Otto, Thomas & Marti, Matthias

Differential expression (DE) - Comparison of gene expression of different parasite stages across between different organs (spleen, blood, bone marrow), using the settings specified in our publication (i.e the first 24 principal components and 0.51 as the clustering resolution). Note that the differential gene expression analysis was performed using a different tool in our publication, thus, results might vary slightly.

Results
scRNAseq analysis of P. berghei in reticulocytes and normocytes. A) Annotated UMAP of P. berghei cells. B) Host RNA content (measured by UMI mapping to mouse, MmUMI) across parasite stages. Cells are subsampled to 300 cells per stage. Color of dots indicates CD71 positive (pink) and negative cells (black). Cells with more than 100 MmUMI were defined as reticulocytes (indicated by horizontal line). C) UMAP of P. berghei cells colored by host cell (red: normocytes, blue: reticulocytes) D) Volcano plot of differential gene expression in reticulocyte-infecting parasites versus normocyte-infecting parasites in selected stages. Red: Genes passing the false discover rate (FDR) threshold.

Single gene DE visualization

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Dotplot for multiple gene DE visualization

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DE scatterplot

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DE table

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