Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite

Lindsey B. Turnbull, Geoffrey H. Siwo, Katrina A. Button-Simons, Asako Tan, Lisa A. Checkley, Heather J. Painter, Manuel Llinás, Michael T. Ferdig

Research output: Contribution to journalArticle

1 Citation (Scopus)

Abstract

Gene expression DNA microarrays have been vital for characterizing whole-genome transcriptional profiles. Nevertheless, their effectiveness relies heavily on the accuracy of genome sequences, the annotation of gene structures, and the sequence-dependent performance of individual probes. Currently available gene expression arrays for the malaria parasite Plasmodium falciparum rely on an average of 2 probes per gene, usually positioned near the 3 0 end of genes; consequently, existing designs are prone to measurement bias and cannot capture complexities such as the occurrence of transcript isoforms arising from alternative splicing or alternative start/ stop sites. Here, we describe two novel gene expression arrays with exon-focused probes designed with an average of 12 and 20 probes spanning each gene. This high probe density minimizes signal noise inherent in probe-to-probe sequence-dependent hybridization intensity. We demonstrate that these exon arrays accurately profile genome-wide expression, comparing favorably to currently available arrays and RNA-seq profiling, and can detect alternatively spliced transcript isoforms as well as non-coding RNAs (ncRNAs). Of the 964 candidate alternate splicing events from published RNA-seq studies, 162 are confirmed using the exon array. Furthermore, the exon array predicted 330 previously unidentified alternate splicing events. Gene expression microarrays continue to offer a cost-effective alternative to RNA-seq for the simultaneous monitoring of gene expression and alternative splicing events. Microarrays may even be preferred in some cases due to their affordability and the rapid turn-around of results when hundreds of samples are required for fine-scale systems biology investigations, including the monitoring of the networks of gene co-expression in the emergence of drug resistance.

Original languageEnglish (US)
Article numbere0187595
JournalPloS one
Volume12
Issue number11
DOIs
StatePublished - Nov 2017

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Gene expression
malaria
probes (equipment)
Malaria
Alternative Splicing
Protein Isoforms
Parasites
Genes
Genome
Exons
Gene Expression
parasites
gene expression
genome
exons
alternative splicing
RNA
Microarrays
Molecular Sequence Annotation
Untranslated RNA

All Science Journal Classification (ASJC) codes

  • Biochemistry, Genetics and Molecular Biology(all)
  • Agricultural and Biological Sciences(all)

Cite this

Turnbull, L. B., Siwo, G. H., Button-Simons, K. A., Tan, A., Checkley, L. A., Painter, H. J., ... Ferdig, M. T. (2017). Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite. PloS one, 12(11), [e0187595]. https://doi.org/10.1371/journal.pone.0187595
Turnbull, Lindsey B. ; Siwo, Geoffrey H. ; Button-Simons, Katrina A. ; Tan, Asako ; Checkley, Lisa A. ; Painter, Heather J. ; Llinás, Manuel ; Ferdig, Michael T. / Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite. In: PloS one. 2017 ; Vol. 12, No. 11.
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Turnbull, LB, Siwo, GH, Button-Simons, KA, Tan, A, Checkley, LA, Painter, HJ, Llinás, M & Ferdig, MT 2017, 'Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite', PloS one, vol. 12, no. 11, e0187595. https://doi.org/10.1371/journal.pone.0187595

Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite. / Turnbull, Lindsey B.; Siwo, Geoffrey H.; Button-Simons, Katrina A.; Tan, Asako; Checkley, Lisa A.; Painter, Heather J.; Llinás, Manuel; Ferdig, Michael T.

In: PloS one, Vol. 12, No. 11, e0187595, 11.2017.

Research output: Contribution to journalArticle

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Turnbull LB, Siwo GH, Button-Simons KA, Tan A, Checkley LA, Painter HJ et al. Simultaneous genome-wide gene expression and transcript isoform profiling in the human malaria parasite. PloS one. 2017 Nov;12(11). e0187595. https://doi.org/10.1371/journal.pone.0187595