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

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

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. / Andradi-Brown, Clare; Wichers-Misterek, Jan Stephan; von Thien, Heidrun; Höppner, Yannick D; Scholz, Judith A M; Hansson, Helle; Filtenborg Hocke, Emma; Gilberger, Tim Wolf; Duffy, Michael F; Lavstsen, Thomas; Baum, Jake; Otto, Thomas D; Cunnington, Aubrey J; Bachmann, Anna.

In: eLife, Vol. 12, RP87726, 25.01.2024.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Andradi-Brown, C, Wichers-Misterek, JS, von Thien, H, Höppner, YD, Scholz, JAM, Hansson, H, Filtenborg Hocke, E, Gilberger, TW, Duffy, MF, Lavstsen, T, Baum, J, Otto, TD, Cunnington, AJ & Bachmann, A 2024, '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', eLife, vol. 12, RP87726. https://doi.org/10.7554/eLife.87726

APA

Andradi-Brown, C., Wichers-Misterek, J. S., von Thien, H., Höppner, Y. D., Scholz, J. A. M., Hansson, H., Filtenborg Hocke, E., Gilberger, T. W., Duffy, M. F., Lavstsen, T., Baum, J., Otto, T. D., Cunnington, A. J., & Bachmann, A. (2024). 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. eLife, 12, [RP87726]. https://doi.org/10.7554/eLife.87726

Vancouver

Andradi-Brown C, Wichers-Misterek JS, von Thien H, Höppner YD, Scholz JAM, Hansson H et al. 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. eLife. 2024 Jan 25;12. RP87726. https://doi.org/10.7554/eLife.87726

Author

Andradi-Brown, Clare ; Wichers-Misterek, Jan Stephan ; von Thien, Heidrun ; Höppner, Yannick D ; Scholz, Judith A M ; Hansson, Helle ; Filtenborg Hocke, Emma ; Gilberger, Tim Wolf ; Duffy, Michael F ; Lavstsen, Thomas ; Baum, Jake ; Otto, Thomas D ; Cunnington, Aubrey J ; Bachmann, Anna. / 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. In: eLife. 2024 ; Vol. 12.

Bibtex

@article{5f60558a06f742558f576905a9826bdd,
title = "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",
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.",
keywords = "Humans, Plasmodium falciparum/genetics, Transcriptome, Malaria, Falciparum, Benchmarking, Emotions",
author = "Clare Andradi-Brown and Wichers-Misterek, {Jan Stephan} and {von Thien}, Heidrun and H{\"o}ppner, {Yannick D} and Scholz, {Judith A M} and Helle Hansson and {Filtenborg Hocke}, Emma and Gilberger, {Tim Wolf} and Duffy, {Michael F} and Thomas Lavstsen and Jake Baum and Otto, {Thomas D} and Cunnington, {Aubrey J} and Anna Bachmann",
note = "{\textcopyright} 2023, Andradi-Brown et al.",
year = "2024",
month = jan,
day = "25",
doi = "10.7554/eLife.87726",
language = "English",
volume = "12",
journal = "eLife",
issn = "2050-084X",
publisher = "eLife Sciences Publications Ltd.",

}

RIS

TY - JOUR

T1 - 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

AU - Andradi-Brown, Clare

AU - Wichers-Misterek, Jan Stephan

AU - von Thien, Heidrun

AU - Höppner, Yannick D

AU - Scholz, Judith A M

AU - Hansson, Helle

AU - Filtenborg Hocke, Emma

AU - Gilberger, Tim Wolf

AU - Duffy, Michael F

AU - Lavstsen, Thomas

AU - Baum, Jake

AU - Otto, Thomas D

AU - Cunnington, Aubrey J

AU - Bachmann, Anna

N1 - © 2023, Andradi-Brown et al.

PY - 2024/1/25

Y1 - 2024/1/25

N2 - 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.

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% 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.

KW - Humans

KW - Plasmodium falciparum/genetics

KW - Transcriptome

KW - Malaria, Falciparum

KW - Benchmarking

KW - Emotions

U2 - 10.7554/eLife.87726

DO - 10.7554/eLife.87726

M3 - Journal article

C2 - 38270586

VL - 12

JO - eLife

JF - eLife

SN - 2050-084X

M1 - RP87726

ER -

ID: 380578512