Spin models inferred from patient-derived viral sequence data faithfully describe HIV fitness landscapes
Abstract
Mutational escape from vaccine-induced immune responses has thwarted the development of a successful vaccine against AIDS, whose causative agent is HIV, a highly mutable virus. Knowing the virus' fitness as a function of its proteomic sequence can enable rational design of potent vaccines, as this information can focus vaccine-induced immune responses to target mutational vulnerabilities of the virus. Spin models have been proposed as a means to infer intrinsic fitness landscapes of HIV proteins from patient-derived viral protein sequences. These sequences are the product of nonequilibrium viral evolution driven by patient-specific immune responses and are subject to phylogenetic constraints. How can such sequence data allow inference of intrinsic fitness landscapes? We combined computer simulations and variational theory á la Feynman to show that, in most circumstances, spin models inferred from patient-derived viral sequences reflect the correct rank order of the fitness of mutant viral strains. Our findings are relevant for diverse viruses.
- Publication:
-
Physical Review E
- Pub Date:
- December 2013
- DOI:
- 10.1103/PhysRevE.88.062705
- arXiv:
- arXiv:1306.2029
- Bibcode:
- 2013PhRvE..88f2705S
- Keywords:
-
- 87.10.-e;
- 87.19.xd;
- 87.18.Vf;
- 87.23.Cc;
- General theory and mathematical aspects;
- Viral diseases;
- Systems biology;
- Population dynamics and ecological pattern formation;
- Physics - Biological Physics;
- Quantitative Biology - Populations and Evolution
- E-Print:
- 10 pages, 4 figures and supplementary methods file