St Petersburg University geneticists develop the world’s first bioinformatic tool to identify amyloids consisting of multiple proteins

Amyloids are protein aggregates that are associated with a number of severe and incurable diseases, such as Alzheimer’s, Parkinson’s, and Huntington’s to name just a few. Yet, the presence of amyloid is not always pathological; many of them have functional, ‘beneficial’ roles in cells. What can trigger aggregation into amyloid fibrils is changes in protein structure, scientists say. In the last few years, however, a considerable body of data has been accumulated about co-aggregation of different amyloid-forming proteins.

The findings of the research supported by a grant from the Russian Science Foundation are published in the Journal of Molecular Biology.

The team of geneticists and biotechnologists from St Petersburg University and the University of Montpellier (France) was the first in the world to propose a bioinformatics approach AmyloComp to identify pairs of proteins capable of co-aggregation, i.e. binding with each other. The software is written in the Python programming language and is available as an online application. 

"Amyloid look like fibrils. They form a kind of «stack» of many molecules located across the fibre. Traditionally, amyloid fibrils consist of multiple copies of the same protein. In this case, they are homogeneous and have the same structure. Yet, what we are trying to find is co-aggregation of different proteins in a common fibril, i.e. a stacking of different proteins within the same amyloid fibril," said Stanislav Bondarev, co-author of the study, Associate Professor in the Department of Genetics and Biotechnology at St Petersburg University. 

According to Stanislav Bondarev, the AmyloComp software developed by the University scientists demonstrates an accuracy of more than 94% on a model data set and also reliably classifies known positive and negative examples of protein co-aggregation. Thus, protein co-aggregation can play various biological roles in the body. 

On the one hand, the "amyloid cascade" hypothesis was proposed quite a long time ago. The hypothesis assumes that pathological amyloid aggregates can trigger the aggregation of other proteins. On the other hand, some important biological processes require co-aggregation of different amyloid-forming proteins. Among known examples of the co-aggregation are human proteins RIPK1 and RIPK3. This co-aggregation is part of the signalling cascade when triggering the antiviral response. The AmyloComp software can identify similar examples on the proteome scale. 

The bioinformatic tool is unique. Other bioinformatic approaches do not model co-aggregation of two amyloid proteins. The method developed by the St Petersburg University researchers is based on a comparison of the amino acid sequence of two proteins and takes into account the possibility of stacking of different proteins within the same amyloid fibril. This approach makes it possible to identify different sequences that form a single structure.

St Petersburg University is the leader in the number of grants from the Russian Science Foundation. In 2022, St Petersburg University researchers received 112 grants, this is 5.5% of the total number of the winning projects and the largest number of grants for one organisation. Additionally, 25% of the supported projects are carried out under the guidance of early-career researchers. In 2023, the University retained its leadership in this contest of the Russian Science Foundation. St Petersburg University researchers received 70 grants, which is 5% of the total number of the winning projects. St Petersburg University submitted 214 applications for the 2023 contests, and almost every third of them received support from the Russian Science Foundation.

The team of scientists in the Department of Genetics and Biotechnology at St Petersburg University is one of the leading research teams that study amyloids in the world. The study of amyloids at St Petersburg University under the leadership of Academician Sergei Inge-Vechtomov began back in the 1990s. A number of world-class breakthrough works were published on infectious amyloids (prions) of yeast. Later, a laboratory of amyloid biology was opened at the University. It was headed by Aleksandr Rubel, who graduated from the Department of Genetics and Biotechnology at the University. 

In 2021, Anton Nizhnikov, Professor in the Department of Genetics and Biotechnology at St Petersburg University, and Kirill Antonets, Leading Research Associate in the Department of Cytology and Histology at St Petersburg University, became laureates of the President of the Russian Federation Prize in the field of science and innovation for young scientists. They received awards for the discovery of amyloid proteins in plants and symbiotic bacteria. At the same time, under the guidance of Professor Alexey Galkin, a number of functional amyloids were described in various animals.