LifePrint: a novel k-tuple distance method for construction of phylogenetic trees
Fabián Reyes-Prieto1, Adda J García-Chéquer1, Hueman Jaimes-Díaz1, Janet Casique-Almazán1, Juana M Espinosa-Lara1, Rosaura Palma-Orozco2, Alfonso Méndez-Tenorio1, Rogelio Maldonado-Rodríguez1, Kenneth L Beattie3
1Laboratory of Biotechnology and Genomic Bioinformatics, Department of Biochemistry, National School of Biological Sciences, 2Superior School of Computer Sciences, National Polytechnic Institute, Mexico City, Mexico; 3Amerigenics Inc, Crossville, Tennessee, USA
Purpose: Here we describe LifePrint, a sequence alignment-independent k-tuple distance method to estimate relatedness between complete genomes.
Methods: We designed a representative sample of all possible DNA tuples of length 9 (9-tuples). The final sample comprises 1878 tuples (called the LifePrint set of 9-tuples; LPS9) that are distinct from each other by at least two internal and noncontiguous nucleotide differences. For validation of our k-tuple distance method, we analyzed several real and simulated viroid genomes. Using different distance metrics, we scrutinized diverse viroid genomes to estimate the k-tuple distances between these genomic sequences. Then we used the estimated genomic k-tuple distances to construct phylogenetic trees using the neighbor-joining algorithm. A comparison of the accuracy of LPS9 and the previously reported 5-tuple method was made using symmetric differences between the trees estimated from each method and a simulated “true” phylogenetic tree.
Results: The identified optimal search scheme for LPS9 allows only up to two nucleotide differences between each 9-tuple and the scrutinized genome. Similarity search results of simulated viroid genomes indicate that, in most cases, LPS9 is able to detect single-base substitutions between genomes efficiently. Analysis of simulated genomic variants with a high proportion of base substitutions indicates that LPS9 is able to discern relationships between genomic variants with up to 40% of nucleotide substitution.
Conclusion: Our LPS9 method generates more accurate phylogenetic reconstructions than the previously proposed 5-tuples strategy. LPS9-reconstructed trees show higher bootstrap proportion values than distance trees derived from the 5-tuple method.
Keywords: phylogeny, sequence alignment, similarity search, tuple, viroid
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