is a computational framework for the reconstruction and analysis of networks of mutations involved in the protein's evolution of new or improved functions, a.k.a. protein adaptation.
Mutation networks can be reconstructed from a protein's evolutionary history, either in the from a multiple sequence alignment or a Bayesian phylogenetic tree ensemble. Nodes are linked in the network when the corresponding mutations are found to co-occur in the alignment or along phylogenetic tree branches. For a phylogeny based network, the links can also be directed, based on observed ordering of pairs of mutations along the tree branches.
After network reconstruction graph-theoretical analysis can be performed to model properties of a protein's adaptive evolution:
You can view the current source code on github.
Beleva Guthrie V, Masica DL, Fraser A, Federico J, Fan Y, Camps M, and Karchin R (2018). Network Analysis of Protein Adaptation: modeling the functional impact of multiple mutations. Mol. Biol. Evo https://doi.org/10.1093/molbev/msy036
Beleva Guthrie V, Allen J, Camps M, and Karchin R (2011) Network models of TEM β-lactamase mutations coevolving under antibiotic selection show modular structure and anticipate evolutionary trajectories. PLoS Computational Biology. 7(9):e1002184
Violeta Beleva Guthrie: vbeleva at jhu dot edu