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dc.contributor.authorVan Tyne, Dariaen_US
dc.contributor.authorTan, Yanen_US
dc.contributor.authorDaily, Johanna Pen_US
dc.contributor.authorKamiza, Steveen_US
dc.contributor.authorSeydel, Karlen_US
dc.contributor.authorTaylor, Terrieen_US
dc.contributor.authorMesirov, Jill Pen_US
dc.contributor.authorWirth, Dyann Fen_US
dc.contributor.authorMilner, Danny Aen_US
dc.date.accessioned2015-01-05T18:26:30Z
dc.date.issued2014en_US
dc.identifier.citationVan Tyne, Daria, Yan Tan, Johanna P Daily, Steve Kamiza, Karl Seydel, Terrie Taylor, Jill P Mesirov, Dyann F Wirth, and Danny A Milner. 2014. “Plasmodium falciparum gene expression measured directly from tissue during human infection.” Genome Medicine 6 (11): 110. doi:10.1186/s13073-014-0110-6. http://dx.doi.org/10.1186/s13073-014-0110-6.en
dc.identifier.issn1756-994Xen
dc.identifier.urihttp://nrs.harvard.edu/urn-3:HUL.InstRepos:13581053
dc.description.abstractBackground: During the latter half of the natural 48-h intraerythrocytic life cycle of human Plasmodium falciparum infection, parasites sequester deep in endothelium of tissues, away from the spleen and inaccessible to peripheral blood. These late-stage parasites may cause tissue damage and likely contribute to clinical disease, and a more complete understanding of their biology is needed. Because these life cycle stages are not easily sampled due to deep tissue sequestration, measuring in vivo gene expression of parasites in the trophozoite and schizont stages has been a challenge. Methods: We developed a custom nCounter® gene expression platform and used this platform to measure malaria parasite gene expression profiles in vitro and in vivo. We also used imputation to generate global transcriptional profiles and assessed differential gene expression between parasites growing in vitro and those recovered from malaria-infected patient tissues collected at autopsy. Results: We demonstrate, for the first time, global transcriptional expression profiles from in vivo malaria parasites sequestered in human tissues. We found that parasite physiology can be correlated with in vitro data from an existing life cycle data set, and that parasites in sequestered tissues show an expected schizont-like transcriptional profile, which is conserved across tissues from the same patient. Imputation based on 60 landmark genes generated global transcriptional profiles that were highly correlated with genome-wide expression patterns from the same samples measured by microarray. Finally, differential expression revealed a limited set of in vivo upregulated transcripts, which may indicate unique parasite genes involved in human clinical infections. Conclusions: Our study highlights the utility of a custom nCounter® P. falciparum probe set, validation of imputation within Plasmodium species, and documentation of in vivo schizont-stage expression patterns from human tissues. Electronic supplementary material The online version of this article (doi:10.1186/s13073-014-0110-6) contains supplementary material, which is available to authorized users.en
dc.language.isoen_USen
dc.publisherBioMed Centralen
dc.relation.isversionofdoi:10.1186/s13073-014-0110-6en
dc.relation.hasversionhttp://www.ncbi.nlm.nih.gov/pmc/articles/PMC4269068/pdf/en
dash.licenseLAAen_US
dc.titlePlasmodium falciparum gene expression measured directly from tissue during human infectionen
dc.typeJournal Articleen_US
dc.description.versionVersion of Recorden
dc.relation.journalGenome Medicineen
dash.depositing.authorWirth, Dyann Fen_US
dc.date.available2015-01-05T18:26:30Z
dc.identifier.doi10.1186/s13073-014-0110-6*
dash.contributor.affiliatedMilner, Danny
dash.contributor.affiliatedWirth, Dyann


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