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Weighted Statistical Binning: enabling statistically consistent genome-scale phylogenetic analyses

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 Publication date 2014
  fields Biology
and research's language is English




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Because biological processes can make different loci have different evolutionary histories, species tree estimation requires multiple loci from across the genome. While many processes can result in discord between gene trees and species trees, incomplete lineage sorting (ILS), modeled by the multi-species coalescent, is considered to be a dominant cause for gene tree heterogeneity. Coalescent-based methods have been developed to estimate species trees, many of which operate by combining estimated gene trees, and so are called summary methods. Because summary methods are generally fast, they have become very popular techniques for estimating species trees from multiple loci. However, recent studies have established that summary methods can have reduced accuracy in the presence of gene tree estimation error, and also that many biological datasets have substantial gene tree estimation error, so that summary methods may not be highly accurate on biologically realistic conditions. Mirarab et al. (Science 2014) presented the statistical binning technique to improve gene tree estimation in multi-locus analyses, and showed that it improved the accuracy of MP-EST, one of the most popular coalescent-based summary methods. Statistical binning, which uses a simple statistical test for combinability and then uses the larger sets of genes to re-calculate gene trees, has good empirical performance, but using statistical binning within a phylogenomics pipeline does not have the desirable property of being statistically consistent. We show that weighting the recalculated gene trees by the bin sizes makes statistical binning statistically consistent under the multispecies coalescent, and maintains the good empirical performance. Thus, weighted statistical binning enables highly accurate genome-scale species tree estimation, and is also statistical consistent under the multi-species coalescent model.



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Metagenomic binning is an essential task in analyzing metagenomic sequence datasets. To analyze structure or function of microbial communities from environmental samples, metagenomic sequence fragments are assigned to their taxonomic origins. Although sequence alignment algorithms can readily be used and usually provide high-resolution alignments and accurate binning results, the computational cost of such alignment-based methods becomes prohibitive as metagenomic datasets continue to grow. Alternative compositional-based methods, which exploit sequence composition by profiling local short k-mers in fragments, are often faster but less accurate than alignment-based methods. Inspired by the success of linear error correcting codes in noisy channel communication, we introduce Opal, a fast and accurate novel compositional-based binning method. It incorporates ideas from Gallagers low-density parity-check code to design a family of compact and discriminative locality-sensitive hashing functions that encode long-range compositional dependencies in long fragments. By incorporating the Gallager LSH functions as features in a simple linear SVM, Opal provides fast, accurate and robust binning for datasets consisting of a large number of species, even with mutations and sequencing errors. Opal not only performs up to two orders of magnitude faster than BWA, an alignment-based binning method, but also achieves improved binning accuracy and robustness to sequencing errors. Opal also outperforms models built on traditional k-mer profiles in terms of robustness and accuracy. Finally, we demonstrate that we can effectively use Opal in the coarse search stage of a compressive genomics pipeline to identify a much smaller candidate set of taxonomic origins for a subsequent alignment-based method to analyze, thus providing metagenomic binning with high scalability, high accuracy and high resolution.
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