Integrative proteomics to illuminate host–parasite interactions in malaria

Genomic studies have transformed malaria research but provide only indirect proxies for the functional processes that govern infection progression and clinical outcomes. We argue that proteomics should be a core component of malaria systems biology. By quantifying protein abundance, post-translational modifications, interaction networks, localization, and turnover in both host and parasite, proteomics can help identify mechanisms of cytoadhesion, endothelial dysfunction, immune modulation, tissue-specific pathology, and variability in therapeutic response—processes less amenable to interrogation at the nucleic acid level. Advances in high-throughput and high-resolution proteomic technologies, as well as emerging single-cell and spatial proteomics combined with artificial intelligence-driven pipelines, now enable comprehensive, sensitive, quantitative, system-wide profiling. We outline how these approaches can dissect host–parasite crosstalk and accelerate discovery in malaria research.