The malarial blood transcriptome: translational applications

Abstract

The blood transcriptome of malaria patients has been used extensively to elucidate the pathophysiological mechanisms and host immune responses to disease, identify candidate diagnostic and prognostic biomarkers, and reveal new therapeutic targets for drug discovery. This review gives a high-level overview of the three main translational applications of these studies (diagnostics, prognostics, and therapeutics) by summarising recent literature and outlining the main limitations and future directions of each application. It highlights the need for consistent and accurate definitions of disease states and subject groups and discusses how prognostic studies must distinguish clearly between analyses that attempt to predict future disease states and those which attempt to discriminate between current disease states (classification). Lastly it examines how many promising therapeutics fail due to the choice of imperfect animal models for pre-clinical testing and lack of appropriate validation studies in humans, and how future transcriptional studies may be utilised to overcome some of these limitations.

Keywords: diagnostics; malaria; prognosis; therapeutics; transcriptomics.

Figure 1.. The translational applications of whole-blood transcriptomic studies of malaria.

Whole blood (containing leukocytes, uninfected and infected erythrocytes) is collected from malaria parasite-infected subjects. RNA is extracted and quantified using RNA-sequencing or microarray and then bioinformatic analyses identify genes and biological pathways that could be used for improved diagnostics, prognostics, and therapeutics. Improvements in each of these three applications has potential to benefit development of improvements in the others. This figure was created with BioRender.com.