BrainPepPass: A Framework Based on Supervised Dimensionality Reduction for Predicting Blood-Brain Barrier-Penetrating Peptides.

Peptides that pass through the blood-brain barrier (BBB) not only are implicated in brain-related pathologies but also are promising therapeutic tools for treating brain diseases, e.g., as shuttles carrying active medicines across the BBB. Computational prediction of BBB-penetrating peptides (B3PPs) has emerged as an interesting approach because of its ability to screen large peptide libraries in a cost-effective manner. In this study, we present BrainPepPass, a machine learning (ML) framework that utilizes supervised manifold dimensionality reduction and extreme gradient boosting (XGB) algorithms to predict natural and chemically modified B3PPs. The results indicate that the proposed tool outperforms other classifiers, with average accuracies exceeding 94% and 98% in 10-fold cross-validation and leave-one-out cross-validation (LOOCV), respectively. In addition, accuracy values ranging from 45% to 97.05% were achieved in the independent tests. The BrainPepPass tool is available in a public repository for academic use (https://github.com/ewerton-cristhian/BrainPepPass).

Bacterial Quorum-Sensing Peptides as Immune Modulators Present in Systemic Circulation.

Quorum-sensing peptides (QSPs) are bacterial peptides traditionally considered only as inter-bacterial communication molecules. Recently, their involvement in microbiome-host interactions influencing host diseases such as cancer and sarcopenia were explored. However, it is still unknown to what extent these peptides have the potential to modulate the immune system. In this proof-of-concept study, we screened 89 QSPs for their potential to induce IL-6 and TNFα in murine splenocytes and J774 macrophages. Confirmatory experiments on the positive screening-hits were conducted using murine splenocytes and human PBMCs of different ages. Finally, to investigate the biological relevance of immunomodulatory QSPs, we analysed plasma in a human cohort for the presence of the immunomodulatory QSP Q010. To do this, we used a newly developed UHPLC-MS/MS method. Our findings indicated that specific QSPs activate immune cells in vitro, with Q007, Q010, Q017 and Q212 being the top four screening hits. Q007 and Q010 were affirmed in subsequent confirmatory experiments using murine splenocytes and human PBMCs. Finally, Q010 was detected in human plasma, demonstrating for the first time the presence of an immunomodulatory QSP in human circulation. In conclusion, our data are the first evidence indicating the potential of biologically relevant quorum-sensing peptides to modulate the immune system.