TY  - EJOUR
AU  - Andradi-Brown, Clare
AU  - Wichers-Misterek, Jan Stephan
AU  - von Thien, Heidrun
AU  - Höppner, Yannick D
AU  - Scholz, Judith AM
AU  - Hansson, Helle
AU  - Filtenborg Hocke, Emma
AU  - Gilberger, Tim
AU  - Duffy, Michael F
AU  - Lavstsen, Thomas
AU  - Baum, Jake
AU  - Otto, Thomas D
AU  - Cunnington, Aubrey J.
AU  - Bachmann, Anna
TI  - A novel computational pipeline for var gene expression augments the discovery of changes in the Plasmodium falciparum transcriptome during transition from in vivo to short-term in vitro culture
JO  - eLife
VL  - 12
SN  - 2050-084X
M1  - PUBDB-2024-05640
PY  - 2024
AB  - The pathogenesis of severe Plasmodium falciparum malaria involves cytoadhesive microvascular sequestration of infected erythrocytes, mediated by P. falciparum erythrocyte membrane protein 1 (PfEMP1). PfEMP1 variants are encoded by the highly polymorphic family of var genes, the sequences of which are largely unknown in clinical samples. Previously, we published new approaches for var gene profiling and classification of predicted binding phenotypes in clinical P. falciparum isolates (Wichers et al., 2021), which represented a major technical advance. Building on this, we report here a novel method for var gene assembly and multidimensional quantification from RNA-sequencing that outperforms the earlier approach of Wichers et al., 2021, on both laboratory and clinical isolates across a combination of metrics. Importantly, the tool can interrogate the var transcriptome in context with the rest of the transcriptome and can be applied to enhance our understanding of the role of var genes in malaria pathogenesis. We applied this new method to investigate changes in var gene expression through early transition of parasite isolates to in vitro culture, using paired sets of ex vivo samples from our previous study, cultured for up to three generations. In parallel, changes in non-polymorphic core gene expression were investigated. Modest but unpredictable var gene switching and convergence towards var2csa were observed in culture, along with differential expression of 19
LB  - PUB:(DE-HGF)25
C6  - pmid:38270586
DO  - DOI:10.7554/eLife.87726
UR  - https://bib-pubdb1.desy.de/record/613834
ER  -