SecretTarget: A pipeline for identifying host-interacting effector candidates through secondary localization features

<jats:p>Intracellular parasites cause over 226 million disability-adjusted life years (DALY) globally each year. Current treatment methods fall short of desirable impact due to adverse effects and growing resistance, shifting focus to parasitic effectors for future therapeutic development. Unfortunately, the divergent nature of parasitic proteins has impeded in silico discovery of - and functional inference for - parasitic effectors. Here, we present SecretTarget, a pipeline designed to identify host-interacting effector candidates through secondary localization features. By truncating signal peptides from predicted extracellular proteins (ΔSP), we unmask potential underlying localization features that dictate subcellular trafficking within the host. Applying our pipeline to a set of Toxoplasma gondii secreted effectors with known localizations and interactions, we propose a novel host ER-parasite interaction critical for parasite survival, recapitulate published localizations, and provide meaningful biological insights aligning with recent host-parasite interaction discoveries.</jats:p>