22,598 research outputs found
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
Spaced seeds improve k-mer-based metagenomic classification
Metagenomics is a powerful approach to study genetic content of environmental
samples that has been strongly promoted by NGS technologies. To cope with
massive data involved in modern metagenomic projects, recent tools [4, 39] rely
on the analysis of k-mers shared between the read to be classified and sampled
reference genomes. Within this general framework, we show in this work that
spaced seeds provide a significant improvement of classification accuracy as
opposed to traditional contiguous k-mers. We support this thesis through a
series a different computational experiments, including simulations of
large-scale metagenomic projects. Scripts and programs used in this study, as
well as supplementary material, are available from
http://github.com/gregorykucherov/spaced-seeds-for-metagenomics.Comment: 23 page
Human-chimpanzee alignment: Ortholog Exponentials and Paralog Power Laws
Genomic subsequences conserved between closely related species such as human
and chimpanzee exhibit an exponential length distribution, in contrast to the
algebraic length distribution observed for sequences shared between distantly
related genomes. We find that the former exponential can be further decomposed
into an exponential component primarily composed of orthologous sequences, and
a truncated algebraic component primarily composed of paralogous sequences.Comment: Main text: 31 pages, 13 figures, 1 table; Supplementary materials: 9
pages, 9 figures, 1 tabl
Recovering complete and draft population genomes from metagenome datasets.
Assembly of metagenomic sequence data into microbial genomes is of fundamental value to improving our understanding of microbial ecology and metabolism by elucidating the functional potential of hard-to-culture microorganisms. Here, we provide a synthesis of available methods to bin metagenomic contigs into species-level groups and highlight how genetic diversity, sequencing depth, and coverage influence binning success. Despite the computational cost on application to deeply sequenced complex metagenomes (e.g., soil), covarying patterns of contig coverage across multiple datasets significantly improves the binning process. We also discuss and compare current genome validation methods and reveal how these methods tackle the problem of chimeric genome bins i.e., sequences from multiple species. Finally, we explore how population genome assembly can be used to uncover biogeographic trends and to characterize the effect of in situ functional constraints on the genome-wide evolution
Progressive Mauve: Multiple alignment of genomes with gene flux and rearrangement
Multiple genome alignment remains a challenging problem. Effects of
recombination including rearrangement, segmental duplication, gain, and loss
can create a mosaic pattern of homology even among closely related organisms.
We describe a method to align two or more genomes that have undergone
large-scale recombination, particularly genomes that have undergone substantial
amounts of gene gain and loss (gene flux). The method utilizes a novel
alignment objective score, referred to as a sum-of-pairs breakpoint score. We
also apply a probabilistic alignment filtering method to remove erroneous
alignments of unrelated sequences, which are commonly observed in other genome
alignment methods. We describe new metrics for quantifying genome alignment
accuracy which measure the quality of rearrangement breakpoint predictions and
indel predictions. The progressive genome alignment algorithm demonstrates
markedly improved accuracy over previous approaches in situations where genomes
have undergone realistic amounts of genome rearrangement, gene gain, loss, and
duplication. We apply the progressive genome alignment algorithm to a set of 23
completely sequenced genomes from the genera Escherichia, Shigella, and
Salmonella. The 23 enterobacteria have an estimated 2.46Mbp of genomic content
conserved among all taxa and total unique content of 15.2Mbp. We document
substantial population-level variability among these organisms driven by
homologous recombination, gene gain, and gene loss. Free, open-source software
implementing the described genome alignment approach is available from
http://gel.ahabs.wisc.edu/mauve .Comment: Revision dated June 19, 200
Whole Genome Phylogenetic Tree Reconstruction Using Colored de Bruijn Graphs
We present kleuren, a novel assembly-free method to reconstruct phylogenetic
trees using the Colored de Bruijn Graph. kleuren works by constructing the
Colored de Bruijn Graph and then traversing it, finding bubble structures in
the graph that provide phylogenetic signal. The bubbles are then aligned and
concatenated to form a supermatrix, from which a phylogenetic tree is inferred.
We introduce the algorithms that kleuren uses to accomplish this task, and show
its performance on reconstructing the phylogenetic tree of 12 Drosophila
species. kleuren reconstructed the established phylogenetic tree accurately,
and is a viable tool for phylogenetic tree reconstruction using whole genome
sequences. Software package available at: https://github.com/Colelyman/kleurenComment: 6 pages, 3 figures, accepted at BIBE 2017. Minor modifications to the
text due to reviewer feedback and fixed typo
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