Genomic from Plasmodium falciparum field isolates from Benin allows the identification of PfEMP1 variants by LC-MS/MS at the patient’s level

PfEMP1 are the major protein family from parasitic origin involves in the pathophysiology of severe malaria, and PfEMP1 domain subtypes are associated with the infection outcome. In addition, PfEMP1 variability in endless and current protein repository do not reflect the immense diversity of the sequences of PfEMP1 proteins. The aim of our study was to identify the different PfEMP1 variants expressed within a patient sample by mass spectrometry. We performed a proteogenomic approach to decipher at the patient’s level PfEMP1 expression in different clinical settings: cerebral malaria, severe anemia and uncomplicated malaria. The combination of whole genome sequencing approach, RNAsequencing, and mass spectrometry proteomic analysis allowed to attribute PfEMP1 sequences to each sample and classify the relative expression level of PfEMP1 proteins within each sample. We predicted PfEMP1 structures using the newly identified protein sequences. We confirmed the involvement of DBLβ in malaria pathogenesis and observed that CIDRα domains linked to ICAM-1 binding DBLβ domains displayed EPCR binding structure.