Alignment-Free Phylogenetic Reconstruction

14th Annual International Conference, RECOMB 2010, Lisbon, Portugal, April 25-28, 2010. ProceedingsWe introduce the first polynomial-time phylogenetic reconstruction algorithm under a model of sequence evolution allowing insertions and deletions (or indels). Given appropriate assumptions, our algorithm requires sequence lengths growing polynomially in the number of leaf taxa. Our techniques are distance-based and largely bypass the problem of multiple alignment

Alignment-free phylogenetic reconstruction: Sample complexity via a branching process analysis

We present an efficient phylogenetic reconstruction algorithm allowing insertions and deletions which provably achieves a sequence-length requirement (or sample complexity) growing polynomially in the number of taxa. Our algorithm is distance-based, that is, it relies on pairwise sequence comparisons. More importantly, our approach largely bypasses the difficult problem of multiple sequence alignment.Comment: Published in at http://dx.doi.org/10.1214/12-AAP852 the Annals of Applied Probability (http://www.imstat.org/aap/) by the Institute of Mathematical Statistics (http://www.imstat.org

Phylogenetic Tree Construction for Starfish and Primate Genomes via Alignment Free Methods

A phylogenetic tree is a tree like diagram showing the evolutionary relationship among various species based on their differences or similarity in their physical or genetic makeup.The similarity in their genetic makeup is traditionally measured based on pairwise distance between their gene sequences using sequence alignment methods. Due to the advancement in next generation sequencing technologies there is a huge amount of datasets available for partially or completely sequenced genomes. These massive datasets requires a faster comparison methods other than the traditional alignment-based approaches. Therefore, alignment free approaches are gaining popularity in recent years. In this thesis, we compare alignment-based and various alignment free methods for phylogenetic tree construction. The alignment free methods we study are based on k-mer frequency, Average Common Substring (ACS) and ACS with position restrictions and mismatches. The position restricted ACS is a novel contribution of this thesis. To evaluate performance of the alignment free approaches we applied it to phylogeny reconstruction using DNA ( 27 primate mitochondrial genomes) and protein (Starfish RNA-seq) sequence sets. The phylogenetic trees are constructed using Neighbor joining to the distance matrices obtained with the above mentioned alignment-free methods. The resulting phylogenetic trees are then compared with the reference tree using Branch Score Distance measure. Both the Neighbor joining and the Branch Score Distance Measure are calculated by using the programs neighbor and treedist from the PHYLIP package

Accurate Reconstruction of Molecular Phylogenies for Proteins Using Codon and Amino Acid Unified Sequence Alignments (CAUSA)

Based on molecular clock hypothesis, and neutral theory of molecular evolution, molecular phylogenies have been widely used for inferring evolutionary history of organisms and individual genes. Traditionally, alignments and phylogeny trees of proteins and their coding DNA sequences are constructed separately, thus often different conclusions were drawn. Here we present a new strategy for sequence alignment and phylogenetic tree reconstruction, codon and amino acid unified sequence alignment (CAUSA), which aligns DNA and protein sequences and draw phylogenetic trees in a unified manner. We demonstrated that CAUSA improves both the accuracy of multiple sequence alignments and phylogenetic trees by solving a variety of molecular evolutionary problems in virus, bacteria and mammals. Our results support the hypothesis that the molecular clock for proteins has two pointers existing separately in DNA and protein sequences. It is more accurate to read the molecular clock by combination (additive) of these two pointers, since the ticking rates of them are sometimes consistent, sometimes different. CAUSA software were released as Open Source under GNU/GPL license, and are downloadable free of charge from the website www.dnapluspro.com

Alignment-free sequence comparison with spaced k-mers

Alignment-free methods are increasingly used for genome analysis and phylogeny reconstruction since they circumvent various difficulties of traditional approaches that rely on multiple sequence alignments. In particular, they are much faster than alignment-based methods. Most alignment-free approaches work by analyzing the k-mer composition of sequences. In this paper, we propose to use \u27spaced k-mers\u27, i.e. patterns of deterministic and \u27don\u27t care\u27 positions instead of contiguous k-mers. Using simulated and real-world sequence data, we demonstrate that this approach produces better phylogenetic trees than alignment-free methods that rely on contiguous k-mers. In addition, distances calculated with spaced k-mers appear to be statistically more stable than distances based on contiguous k-mers

Accurate reconstruction of insertion-deletion histories by statistical phylogenetics

The Multiple Sequence Alignment (MSA) is a computational abstraction that represents a partial summary either of indel history, or of structural similarity. Taking the former view (indel history), it is possible to use formal automata theory to generalize the phylogenetic likelihood framework for finite substitution models (Dayhoff's probability matrices and Felsenstein's pruning algorithm) to arbitrary-length sequences. In this paper, we report results of a simulation-based benchmark of several methods for reconstruction of indel history. The methods tested include a relatively new algorithm for statistical marginalization of MSAs that sums over a stochastically-sampled ensemble of the most probable evolutionary histories. For mammalian evolutionary parameters on several different trees, the single most likely history sampled by our algorithm appears less biased than histories reconstructed by other MSA methods. The algorithm can also be used for alignment-free inference, where the MSA is explicitly summed out of the analysis. As an illustration of our method, we discuss reconstruction of the evolutionary histories of human protein-coding genes.Comment: 28 pages, 15 figures. arXiv admin note: text overlap with arXiv:1103.434

Evaluation of phylogenetic reconstruction methods using bacterial whole genomes: a simulation based study

Background: Phylogenetic reconstruction is a necessary first step in many analyses which use whole genome sequence data from bacterial populations. There are many available methods to infer phylogenies, and these have various advantages and disadvantages, but few unbiased comparisons of the range of approaches have been made. Methods: We simulated data from a defined "true tree" using a realistic evolutionary model. We built phylogenies from this data using a range of methods, and compared reconstructed trees to the true tree using two measures, noting the computational time needed for different phylogenetic reconstructions. We also used real data from Streptococcus pneumoniae alignments to compare individual core gene trees to a core genome tree. Results: We found that, as expected, maximum likelihood trees from good quality alignments were the most accurate, but also the most computationally intensive. Using less accurate phylogenetic reconstruction methods, we were able to obtain results of comparable accuracy; we found that approximate results can rapidly be obtained using genetic distance based methods. In real data we found that highly conserved core genes, such as those involved in translation, gave an inaccurate tree topology, whereas genes involved in recombination events gave inaccurate branch lengths. We also show a tree-of-trees, relating the results of different phylogenetic reconstructions to each other. Conclusions: We recommend three approaches, depending on requirements for accuracy and computational time. Quicker approaches that do not perform full maximum likelihood optimisation may be useful for many analyses requiring a phylogeny, as generating a high quality input alignment is likely to be the major limiting factor of accurate tree topology. We have publicly released our simulated data and code to enable further comparisons

Evolutionary distances in the twilight zone -- a rational kernel approach

Phylogenetic tree reconstruction is traditionally based on multiple sequence alignments (MSAs) and heavily depends on the validity of this information bottleneck. With increasing sequence divergence, the quality of MSAs decays quickly. Alignment-free methods, on the other hand, are based on abstract string comparisons and avoid potential alignment problems. However, in general they are not biologically motivated and ignore our knowledge about the evolution of sequences. Thus, it is still a major open question how to define an evolutionary distance metric between divergent sequences that makes use of indel information and known substitution models without the need for a multiple alignment. Here we propose a new evolutionary distance metric to close this gap. It uses finite-state transducers to create a biologically motivated similarity score which models substitutions and indels, and does not depend on a multiple sequence alignment. The sequence similarity score is defined in analogy to pairwise alignments and additionally has the positive semi-definite property. We describe its derivation and show in simulation studies and real-world examples that it is more accurate in reconstructing phylogenies than competing methods. The result is a new and accurate way of determining evolutionary distances in and beyond the twilight zone of sequence alignments that is suitable for large datasets.Comment: to appear in PLoS ON

Pattern-based phylogenetic distance estimation and tree reconstruction

We have developed an alignment-free method that calculates phylogenetic distances using a maximum likelihood approach for a model of sequence change on patterns that are discovered in unaligned sequences. To evaluate the phylogenetic accuracy of our method, and to conduct a comprehensive comparison of existing alignment-free methods (freely available as Python package decaf+py at http://www.bioinformatics.org.au), we have created a dataset of reference trees covering a wide range of phylogenetic distances. Amino acid sequences were evolved along the trees and input to the tested methods; from their calculated distances we infered trees whose topologies we compared to the reference trees. We find our pattern-based method statistically superior to all other tested alignment-free methods on this dataset. We also demonstrate the general advantage of alignment-free methods over an approach based on automated alignments when sequences violate the assumption of collinearity. Similarly, we compare methods on empirical data from an existing alignment benchmark set that we used to derive reference distances and trees. Our pattern-based approach yields distances that show a linear relationship to reference distances over a substantially longer range than other alignment-free methods. The pattern-based approach outperforms alignment-free methods and its phylogenetic accuracy is statistically indistinguishable from alignment-based distances.Comment: 21 pages, 3 figures, 2 table