Work

Proteomics Pipeline for Identifying Variant Proteins in Plasmodium falciparum Parasites Isolated from Children Presenting with Malaria

Year: 2019

Type: article

Abstract: Plasmodium falciparum variant antigens named erythrocyte membrane protein 1 (PfEMP1) are important targets for developing a protective immunity to malaria caused by P. falciparum . One of the major challenges in P. falciparum proteomics studies is identifying PfEMP1s at the protein level due to antigenic variation. To identify these PfEMP1s using shotgun proteomics, we developed a pipeline that searches high-resolution mass spectrometry spectra against a custom protein sequence database. A local alignment algorithm, LAX, was developed as a part of the pipeline that matches peptide sequences to the most similar PfEMP1 and calculates a weight value based on peptide’s uniqueness used for PfEMP1 protein inference. The pipeline was first validated in the analysis of a laboratory strain with a known PfEMP1, then it was implemented on the analysis of parasite isolates from malaria-infected pregnant women and finally on the analysis of parasite isolates from malaria-infected children where there was an increase of PfEMP1s identified in 27 out of 31 isolates using the expanded database.

Source: Journal of Proteome Research

DOI: 10.1021/acs.jproteome.9b00169