Building evolutionary networks of serial samples via a recombination detection approach

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Sliding MinPD combines a minimum pairwise distance approach with automated recombination detection to study the ancestor-descendant relationships of serially-sampled nucleotide sequences. The method presents the results in an evolutionary network structure that respects the time order of the sampled data, represents genetic distances and linking relationships, and indicates recombination events and breakpoint positions.

In Sliding MinPD the identification of recombinants, ancestors and breakpoints is automated with no need for user input. Three existing methods, all of them using the sliding window approach, were implemented as user options in Sliding MinPD:

• Recombination Identification Program (RIP): Similarity between two sequences is quantified as the percentage of identical base pairs [1]. Sliding MinPD does not use a similarity score, but instead uses a corrected distance measure that incorporates rate heterogeneity and substitution patterns to correct for the estimation bias of counting only mismatches among sites

• The standard Bootscanning method (SB): Bootstrapped phylogenetic trees are built for each window segment and finally the bootstrap value for placing the query sequence with each of the reference sequences/sequence groups is tabulated and plotted along the sequence [2]. It requires a minimum of 4 sequences. In Sliding MinPD, Neighbor-Joining trees are constructed from the bootstrapped corrected distance matrices calculated during the RIP process (see above). The pairwise sequence position within the tree is stored in a topology distance matrix. 

• The distance Bootscanning method (B-RIP): This alternative approach to the standard Bootscanning was implemented in RDP2 [3]. Here only the bootstrapped corrected distances are calculated and plotted in the graph (instead of constructing the trees and calculating the position within the trees). 

The significant modification introduced in Sliding MinPD is the automation of these methods, thus eliminating user interaction to identify recombinant sequences and to determine the ancestral donor sequences and breakpoints. The automated identification of recombinants is necessary for the reconstruction of the evolutionary network.

References

[1] Siepel, A. and Korber, B. (1995). Scanning the Database for Recombinant HIV-1 Genomes. Pp. 35-60. Los Alamos National Laboratory

[2] Salminen, M., Carr, J., Burke, D., and McCutchan, F. (1995). Identification of recombination breakpoints in HIV-1 by bootscanning. AIDS Res. Hum. Retroviruses 11:1423–1425

[3] Martin, D. P., Williamson, C., and Posada, D. (2005). RDP2: recombination detection and analysis from sequence alignments. Bioinformatics 21:260-262