Journal article

Integrated pathogen load and dual transcriptome analysis of systemic host-pathogen interactions in severe malaria

HJ Lee, A Georgiadou, M Walther, D Nwakanma, LB Stewart, M Levin, TD Otto, DJ Conway, LJ Coin, AJ Cunnington

Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2018

Abstract

The pathogenesis of infectious diseases depends on the interaction of host and pathogen. In Plasmodium falciparum malaria, host and parasite processes can be assessed by dual RNA sequencing of blood from infected patients. We performed dual transcriptome analyses on samples from 46 malaria-infected Gambian children to reveal mechanisms driving the systemic pathophysiology of severe malaria. Integrating these transcriptomic data with estimates of parasite load and detailed clinical information allowed consideration of potentially confounding effects due to differing leukocyte proportions in blood, parasite developmental stage, and whole-body pathogen load. We report hundreds of human and para..

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University of Melbourne Researchers

Grants

Awarded by Medical Research Council Canada


Funding Acknowledgements

This work was funded by the UK MRC and the UK Department for International Development (DFID) under the MRC/DFID Concordat agreement and is also part of the EDCTP2 program supported by the European Union (MR/L006529/1 to A.J.C.), the European Research Council (AdG-2011-294428 to D.J.C. and L.B.S.), MRC core funding of the MRCG, and the Wellcome Trust (098051 to A.J.C.). Exeter Sequencing Service is supported by an MRC Clinical Infrastructure award (MR/M008924/1), the Wellcome Trust Institutional Strategic Support Fund (WT097835MF), a Wellcome Trust Multi-User Equipment Award (WT101650MA), and a Biotechnology and Biological Sciences Research Council Longer and Larger award (BB/K003240/1).