Metabolomics in the fight against malaria

Abstract

Metabolomics uses high-resolution mass spectrometry to provide a chemical fingerprint of thousands of metabolites present in cells, tissues or body fluids. Such metabolic phenotyping has been successfully used to study various biologic processes and disease states. High-resolution metabolomics can shed new light on the intricacies of host-parasite interactions in each stage of the Plasmodium life cycle and the downstream ramifications on the host's metabolism, pathogenesis and disease. Such data can become integrated with other large datasets generated using top-down systems biology approaches and be utilised by computational biologists to develop and enhance models of malaria pathogenesis relevant for identifying new drug targets or intervention strategies. Here, we focus on the promise of metabolomics to complement systems biology approaches in the quest for novel interventions in the fight against malaria. We introduce the Malaria Host-Pathogen Interaction Center (MaHPIC), a new systems biology research coalition. A primary goal of the MaHPIC is to generate systems biology datasets relating to human and non-human primate (NHP) malaria parasites and their hosts making these openly available from an online relational database. Metabolomic data from NHP infections and clinical malaria infections from around the world will comprise a unique global resource.

Fig. 1. : this Manhattan plot depicts false detection ratio (FDR) analysis of 1,168 mass to charge ratio (m/z) features comparing 26 patients and 19 controls. The negative log p-value is plotted against the m/z features. The x-axis represents the m/z of the features, ordered in increasing value from left to right (85-850). The colouring of the symbols is arbitrary. A total of 94 features significantly differed between patients and controls at an FDR of q = 0.05 (above horizontal dashed line). Adapted from Osborn et al. (2013).

Fig. 2. : Malaria Host-Pathogen Interaction Center (MaHPIC) workflow overview. Non-human primate (NHP) experiments carried out by the Malaria Core produce samples (whole blood, plasma, bone marrow and cell extracts) to be analysed by various MaHPIC scientific cores; several cores are depicted here by round symbols. Data is catalogued by the Informatics Core and further analysed by all cores as well as the Mathematical Models and Computational Analysis Core. The Metabolomics Core also analyses human plasma samples contributed by collaborators working in malaria endemic areas around the world. CBC: complete blood counts; LIMS: Laboratory Information Management System; m/z: mass to charge ratio; RBC: red blood cells.