Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture
- PMID: 19376968
- PMCID: PMC2670243
- DOI: 10.1073/pnas.0811829106
Statistical estimation of cell-cycle progression and lineage commitment in Plasmodium falciparum reveals a homogeneous pattern of transcription in ex vivo culture
Abstract
We have cultured Plasmodium falciparum directly from the blood of infected individuals to examine patterns of mature-stage gene expression in patient isolates. Analysis of the transcriptome of P. falciparum is complicated by the highly periodic nature of gene expression because small variations in the stage of parasite development between samples can lead to an apparent difference in gene expression values. To address this issue, we have developed statistical likelihood-based methods to estimate cell cycle progression and commitment to asexual or sexual development lineages in our samples based on microscopy and gene expression patterns. In cases subsequently matched for temporal development, we find that transcriptional patterns in ex vivo culture display little variation across patients with diverse clinical profiles and closely resemble transcriptional profiles that occur in vitro. These statistical methods, available to the research community, assist in the design and interpretation of P. falciparum expression profiling experiments where it is difficult to separate true differential expression from cell-cycle dependent expression. We reanalyze an existing dataset of in vivo patient expression profiles and conclude that previously observed discrete variation is consistent with the commitment of a varying proportion of the parasite population to the sexual development lineage.
Conflict of interest statement
The authors declare no conflict of interest.
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Comment in
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In vivo profiles in malaria are consistent with a novel physiological state.Proc Natl Acad Sci U S A. 2009 Jul 7;106(27):E70; author reply E71-2. doi: 10.1073/pnas.0904478106. Epub 2009 Jul 1. Proc Natl Acad Sci U S A. 2009. PMID: 19570993 Free PMC article. No abstract available.
References
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- Siau A, et al. Whole-transcriptome analysis of Plasmodium falciparum field isolates: Identification of new pathogenicity factors. J Infect Dis. 2007;196:1603–1612. - PubMed
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