MaHPIC malaria systems biology data from Plasmodium cynomolgi sporozoite longitudinal infections in macaques

Abstract

Plasmodium cynomolgi causes zoonotic malarial infections in Southeast Asia and this parasite species is important as a model for Plasmodium vivax and Plasmodium ovale. Each of these species produces hypnozoites in the liver, which can cause relapsing infections in the blood. Here we present methods and data generated from iterative longitudinal systems biology infection experiments designed and performed by the Malaria Host-Pathogen Interaction Center (MaHPIC) to delve deeper into the biology, pathogenesis, and immune responses of P. cynomolgi in the Macaca mulatta host. Infections were initiated by sporozoite inoculation. Blood and bone marrow samples were collected at defined timepoints for biological and computational experiments and integrative analyses revolving around primary illness, relapse illness, and subsequent disease and immune response patterns. Parasitological, clinical, haematological, immune response, and -omic datasets (transcriptomics, proteomics, metabolomics, and lipidomics) including metadata and computational results have been deposited in public repositories. The scope and depth of these datasets are unprecedented in studies of malaria, and they are projected to be a F.A.I.R., reliable data resource for decades.

Fig. 1

Iterative Plasmodium cynomolgi infections in Macaca mulatta. The experimental approach was designed to (1) use P. cynomolgi in a M. mulatta non-human primate host to discover the characteristics of a relapsing infection as a model for the human pathogen P. vivax and (2) explore the dynamics of the host response to infection. Host samples, their associated metadata and resulting experimental data received unique identifiers that were tracked in a LIMS. Raw and analyzed experimental results and associated metadata were validated and made available internally in a relational database for internal use. The depicted process was iterative, and relied upon clinicians, veterinarians, systems biologists, multiple omics experts, data management and informatics experts, malariologists, immunologists, and mathematical modelers to follow the results and generate new models of disease and hypotheses for further validation. All results were deposited in public repositories. Spz – sporozoite inoculation; NHP – nonhuman primates; n – number of NHPs in each experiment. Experiments 23, 24 and 25 utilized the same M. mulatta animals and either the same (homologous) or different (heterologous) P. cynomolgi strain.

Fig. 2

E13 Experimental timeline. The daily and time point sample collections and the administration of antimalarial medication is shown.

Fig. 3

E04 projected ‘idealized’ and “actual’ experimental timeline and TP sample collection. (a) Timeline used to plan the experiment; (b) Figure showing Idealized clinical progression for the infected NHP cohort, and (c) Figure showing actual clinical progression that occurred during the experiment for each NHP in the cohort. b and c are reproduced with changes and permission from the authors under the Creative Commons license CC BY 4.0.

Fig. 4

E23 projected ‘idealized’ and ‘actual’ experimental timeline and TP sample collection. (a) Timeline used to plan the experiment; (b) Figure showing ‘Idealized’ clinical progression for the infected NHP cohort, and (c) Figure showing ‘actual’ clinical progression that occurred during the experiment for each NHP in the cohort. The vertical yellow lines indicate actual timepoints as in Table 2. b and c are reproduced with changes and permission from the authors under the Creative Commons license CC BY 4.0.

Fig. 5

E24 projected ‘idealized’ and ‘actual’ experimental timeline and TP sample collection. (a) Timeline used to plan the experiment; (b) Figure showing Idealized clinical progression for the infected NHP cohort, and (c) Figure showing actual clinical progression that occurred during the experiment for each NHP in the cohort. The vertical yellow lines indicate actual timepoints as in Table 3. b and c are reproduced with changes and permission from the authors under the Creative Commons license CC BY 4.0.

Fig. 6

E25 planned and actual experimental timeline and TP sample collection. (a) Timeline used to plan the experiment; (b) ‘Idealized’ figure showing projected clinical progression for the infected NHP cohort, and (c) ‘Actual’ figure showing clinical progression that occurred during the experiment for each NHP in the cohort. The vertical yellow lines indicate actual timepoints as in Table 4.

Fig. 7

Flow cytometry gating strategy for E23 panel X, Y, Z platelets.