Email updates

Keep up to date with the latest news and content from BMC Evolutionary Biology and BioMed Central.

Open Access Research article

FLU, an amino acid substitution model for influenza proteins

Cuong Cao Dang1, Quang Si Le2*, Olivier Gascuel3 and Vinh Sy Le1

Author Affiliations

1 College of Technology, Vietnam National University Hanoi, 144 Xuan Thuy, Cau Giay, Hanoi, Vietnam

2 Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, CB10 1SA, UK

3 Methodes et Algorithmes pour la Bioinformatique, LIRMM, CNRS, Universite Montpellier II, Montpellier, France

For all author emails, please log on.

BMC Evolutionary Biology 2010, 10:99  doi:10.1186/1471-2148-10-99

Published: 12 April 2010



The amino acid substitution model is the core component of many protein analysis systems such as sequence similarity search, sequence alignment, and phylogenetic inference. Although several general amino acid substitution models have been estimated from large and diverse protein databases, they remain inappropriate for analyzing specific species, e.g., viruses. Emerging epidemics of influenza viruses raise the need for comprehensive studies of these dangerous viruses. We propose an influenza-specific amino acid substitution model to enhance the understanding of the evolution of influenza viruses.


A maximum likelihood approach was applied to estimate an amino acid substitution model (FLU) from ~113, 000 influenza protein sequences, consisting of ~20 million residues. FLU outperforms 14 widely used models in constructing maximum likelihood phylogenetic trees for the majority of influenza protein alignments. On average, FLU gains ~42 log likelihood points with an alignment of 300 sites. Moreover, topologies of trees constructed using FLU and other models are frequently different. FLU does indeed have an impact on likelihood improvement as well as tree topologies. It was implemented in PhyML and can be downloaded from webcite or included in PhyML 3.0 server at webcite.


FLU should be useful for any influenza protein analysis system which requires an accurate description of amino acid substitutions.