Amino acid composition predicts prion activity.

Fayyaz ul Amir Afsar Minhas, Eric D. Ross, Asa Ben-Hur

Abstract: Author summary The determinants of prion formation in proteins that are rich in glutamine and asparagine are still under debate: is the process driven by primary sequence or by amino acid composition? In 2015 Sabate et al. published a paper suggesting that the process is triggered by short amyloid-prone sequences. Their argument was based on the success of their pWALTZ classifier, which uses a database of short peptides with known amyloid forming propensities. To explore the validity of their argument we compared their original scoring matrices with shuffled scoring matrices, and found no decrease in accuracy, suggesting that the success of pWALTZ is the result of the ability of the scoring matrices to capture amino acid composition. Furthermore, we propose a novel machine learning approach with accuracy that is superior to all published prion prediction methods that are currently available, and uses sequence composition alone.