title: LifePrint: a novel k-tuple distance method for construction of phylogenetic trees.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Biotechnology and Genomic Bioinformatics, Department of Biochemistry, National School of Biological Sciences, Mexico City, Mexico.
authors.forename: Fabián
authors.initials: F
authors.lastname: Reyes-Prieto
authors.forename: Adda J
authors.initials: AJ
authors.lastname: García-Chéquer
authors.forename: Hueman
authors.initials: H
authors.lastname: Jaimes-Díaz
authors.forename: Janet
authors.initials: J
authors.lastname: Casique-Almazán
authors.forename: Juana M
authors.initials: JM
authors.lastname: Espinosa-Lara
authors.forename: Rosaura
authors.initials: R
authors.lastname: Palma-Orozco
authors.forename: Alfonso
authors.initials: A
authors.lastname: Méndez-Tenorio
authors.forename: Rogelio
authors.initials: R
authors.lastname: Maldonado-Rodríguez
authors.forename: Kenneth L
authors.initials: KL
authors.lastname: Beattie