Understanding the role of codon usage bias in virus host jump processes through statistical physics
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.