Realistic three dimensional fitness landscapes generated by self organizing maps for the analysis of experimental HIV-1 evolution

PLoS One. 2014 Feb 28;9(2):e88579. doi: 10.1371/journal.pone.0088579. eCollection 2014.

Abstract

Human Immunodeficiency Virus type 1 (HIV-1) because of high mutation rates, large population sizes, and rapid replication, exhibits complex evolutionary strategies. For the analysis of evolutionary processes, the graphical representation of fitness landscapes provides a significant advantage. The experimental determination of viral fitness remains, in general, difficult and consequently most published fitness landscapes have been artificial, theoretical or estimated. Self-Organizing Maps (SOM) are a class of Artificial Neural Network (ANN) for the generation of topological ordered maps. Here, three-dimensional (3D) data driven fitness landscapes, derived from a collection of sequences from HIV-1 viruses after "in vitro" passages and labelled with the corresponding experimental fitness values, were created by SOM. These maps were used for the visualization and study of the evolutionary process of HIV-1 "in vitro" fitness recovery, by directly relating fitness values with viral sequences. In addition to the representation of the sequence space search carried out by the viruses, these landscapes could also be applied for the analysis of related variants like members of viral quasiespecies. SOM maps permit the visualization of the complex evolutionary pathways in HIV-1 fitness recovery. SOM fitness landscapes have an enormous potential for the study of evolution in related viruses of "in vitro" works or from "in vivo" clinical studies with human, animal or plant viral infections.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • HIV Infections / virology*
  • HIV-1 / classification
  • HIV-1 / pathogenicity
  • Humans
  • Mutation
  • Neural Networks, Computer*
  • Phylogeny

Grants and funding

Work in CNM is supported by grant SAF 2007-61036 and 2010-17226 from MINECO Spain, by grants 36558/06, 36641/07, 36779/08, 360766/09 from FIPSE Spain, and in part by the RETIC de Investigación en SIDA (Red de grupos 173) of the Fondo de Investigaciones Sanitarias (FISss). Work in UCM is supported by grants BFU 2009-12895-C02-02 MICINN and BFU2012-39816-C02-02 from MINECO (Spain). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.