GRASSHOPPER · understandinG the Role of codon usAge biaS in viruS HOst jumP ProcessEs thRough statistical physics
Horizon 2020 — Marie Skłodowska-Curie Actions
- Duration
- 2021-10-01 → 2023-09-30
- EU contribution
- €184,708
- Participants
- 1
- Scheme
- MSCA-IF
Lines connect the coordinator with its partners.
Results in brief
understandinG the Role of codon usAge biaS in viruS HOst jumP ProcessEs thRough statistical physics
There are several forces that shape nucleotide usage in viral genomes. For instance, some motifs are more likely to be recognized by the host's immune system, and are therefore generically avoided by viruses. Moreover, the codon usage of viruses is determined by the availability of tRNAs in the host cell, which in turn is influenced by the host's own codon usage. This interplay between host and virus codon usage and the avoidance of motifs recognized by the host's immune system are a key factors in the adaptation of viruses to their hosts. By studying the patterns of nucleotide and codon usage in viral genomes, we can gain insights into the evolutionary processes that shape these genomes, and use this knowledge to develop new tools for tracking emerging pathogens, developing vaccines, and designing antiviral drugs. The aim of this project was to use methods from statistical physics to build new tools to investigate the role of nucleotide and codon usage in the adaptation of human-infecting viruses to their hosts. The project was divided into two main objectives: (1) to develop a method to identify the pressures that each host exerts on the nucleotide and codon usage of its viruses, and (2) to investigate the role of nucleotide and codon usage in host adaptation of human-infecting viruses following host jumps. In addition to the main scientific objectives, the project was also aimed at developing the skills of the researcher, in particular by providing training in the use of statistical physics methods to study biological systems, and in the use of machine learning techniques to analyze genomic data. Both the scientific and the training objectives of the project were successfully achieved, and the fellowship has been instrumental in the researcher's career development: immediately after the end of the project, the fellow joined a startup company as a Senior Data Scientist to perform research on machine-learning-guided development of phage cocktails for the treatment of bacterial infections.
Data: CORDIS, © European Union
Project objective
Assessing the pandemic risk for viruses of zoonotic origin is extremely hard, but its importance motivates a steadily growing interest. The approaches used so far are hindered by the limited knowledge of the complex interactions of viral genomes with human cells. Within the framework of the global research effort to fill this gap, this action aims at unveiling the relevance of specific genomic features, especially those related to the codon usage bias, in the process of viral host jump. Two objectives are established: (i) identify and quantify the host-induced pressures on viral genomes; (ii) use these pressures to quantify the likelihood of host jumps. To address objective (i), the host-induced pressures will be inferred from large public databases of viral genomes, in the spirit of inverse problems in Statistical Physics. The results will be validated through experiments performed in collaboration with an experimental group at Istitut Pasteur (Paris). The results of objective (i) will be used in objective (ii) to take into account the compatibility of the viral genome with the host-induced pressures in a simple model of host jump. The Applicant will benefit from a secondment at University of Basel where he will acquire useful skills for this challenging objective.The ambitious aims of this action will be achieved via a strongly interdisciplinary approach, which will build on the existing skills of the Applicant, who specialized in combinatorial optimization problems and Statistical Physics of disordered systems during his PhD, together with the expertise of the Supervisor on inference and Statistical Physics models applied to biology topics. The proposed project is expected to have practical impact on vaccine strain design and virus surveillance strategies. Moreover, it will allow the Applicant to benefit of a unique training scheme, in contact with several top-level institutions in EU, and in close collaboration with internationally recognized researchers.
Original text from CORDIS.
Participants
- ECOLE NORMALE SUPERIEURE · ParisCoordinatorFrance
Links
Data: CORDIS, © European Union