% IMPORTANT: The following is UTF-8 encoded.  This means that in the presence
% of non-ASCII characters, it will not work with BibTeX 0.99 or older.
% Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or
% “biber”.

@ARTICLE{AndradiBrown:613834,
      author       = {Andradi-Brown, Clare and Wichers-Misterek, Jan Stephan and
                      von Thien, Heidrun and Höppner, Yannick D and Scholz,
                      Judith AM and Hansson, Helle and Filtenborg Hocke, Emma and
                      Gilberger, Tim and Duffy, Michael F and Lavstsen, Thomas and
                      Baum, Jake and Otto, Thomas D and Cunnington, Aubrey J. and
                      Bachmann, Anna},
      title        = {{A} novel computational pipeline for var gene expression
                      augments the discovery of changes in the {P}lasmodium
                      falciparum transcriptome during transition from in vivo to
                      short-term in vitro culture},
      journal      = {eLife},
      volume       = {12},
      issn         = {2050-084X},
      reportid     = {PUBDB-2024-05640},
      pages        = {RP87726},
      year         = {2024},
      abstract     = {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 $19\%$ of the core
                      transcriptome between paired ex vivo and generation 1
                      samples. Our results cast doubt on the validity of the
                      common practice of using short-term cultured parasites to
                      make inferences about in vivo phenotype and behaviour.},
      cin          = {CSSB-BNITM-TG},
      ddc          = {600},
      cid          = {I:(DE-H253)CSSB-BNITM-TG-20210520},
      pnm          = {899 - ohne Topic (POF4-899) / DFG project
                      G:(GEPRIS)323759012 - Analyse der Transkriptionsdynamik von
                      Virulenzfaktoren in klinischen Isolaten des Malariaerregers
                      Plasmodium falciparum (323759012) / DFG project
                      G:(GEPRIS)433302244 - Epigenetische Regulation der
                      Antigenvariation im Malariaerreger Plasmodium falciparum
                      (433302244)},
      pid          = {G:(DE-HGF)POF4-899 / G:(GEPRIS)323759012 /
                      G:(GEPRIS)433302244},
      experiment   = {EXP:(DE-MLZ)NOSPEC-20140101},
      typ          = {PUB:(DE-HGF)16},
      pubmed       = {pmid:38270586},
      doi          = {10.7554/eLife.87726},
      url          = {https://bib-pubdb1.desy.de/record/613834},
}