Dataset Information

Libra: scalable k-mer-based tool for massive all-vs-all metagenome comparisons.

ABSTRACT: Background:Shotgun metagenomics provides powerful insights into microbial community biodiversity and function. Yet, inferences from metagenomic studies are often limited by dataset size and complexity and are restricted by the availability and completeness of existing databases. De novo comparative metagenomics enables the comparison of metagenomes based on their total genetic content. Results:We developed a tool called Libra that performs an all-vs-all comparison of metagenomes for precise clustering based on their k-mer content. Libra uses a scalable Hadoop framework for massive metagenome comparisons, Cosine Similarity for calculating the distance using sequence composition and abundance while normalizing for sequencing depth, and a web-based implementation in iMicrobe (http://imicrobe.us) that uses the CyVerse advanced cyberinfrastructure to promote broad use of the tool by the scientific community. Conclusions:A comparison of Libra to equivalent tools using both simulated and real metagenomic datasets, ranging from 80 million to 4.2 billion reads, reveals that methods commonly implemented to reduce compute time for large datasets, such as data reduction, read count normalization, and presence/absence distance metrics, greatly diminish the resolution of large-scale comparative analyses. In contrast, Libra uses all of the reads to calculate k-mer abundance in a Hadoop architecture that can scale to any size dataset to enable global-scale analyses and link microbial signatures to biological processes.

SUBMITTER: Choi I

PROVIDER: S-EPMC6354030 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Libra: scalable k-mer-based tool for massive all-vs-all metagenome comparisons.

Choi Illyoung I Ponsero Alise J AJ Bomhoff Matthew M Youens-Clark Ken K Hartman John H JH Hurwitz Bonnie L BL

GigaScience 20190201 2

<h4>Background</h4>Shotgun metagenomics provides powerful insights into microbial community biodiversity and function. Yet, inferences from metagenomic studies are often limited by dataset size and complexity and are restricted by the availability and completeness of existing databases. De novo comparative metagenomics enables the comparison of metagenomes based on their total genetic content.<h4>Results</h4>We developed a tool called Libra that performs an all-vs-all comparison of metagenomes f ...[more]

PMID: 30597002

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Project description:Identifying viral sequences in mixed metagenomes containing both viral and host contigs is a critical first step in analyzing the viral component of samples. Current tools for distinguishing prokaryotic virus and host contigs primarily use gene-based similarity approaches. Such approaches can significantly limit results especially for short contigs that have few predicted proteins or lack proteins with similarity to previously known viruses.We have developed VirFinder, the first k-mer frequency based, machine learning method for virus contig identification that entirely avoids gene-based similarity searches. VirFinder instead identifies viral sequences based on our empirical observation that viruses and hosts have discernibly different k-mer signatures. VirFinder's performance in correctly identifying viral sequences was tested by training its machine learning model on sequences from host and viral genomes sequenced before 1 January 2014 and evaluating on sequences obtained after 1 January 2014.VirFinder had significantly better rates of identifying true viral contigs (true positive rates (TPRs)) than VirSorter, the current state-of-the-art gene-based virus classification tool, when evaluated with either contigs subsampled from complete genomes or assembled from a simulated human gut metagenome. For example, for contigs subsampled from complete genomes, VirFinder had 78-, 2.4-, and 1.8-fold higher TPRs than VirSorter for 1, 3, and 5 kb contigs, respectively, at the same false positive rates as VirSorter (0, 0.003, and 0.006, respectively), thus VirFinder works considerably better for small contigs than VirSorter. VirFinder furthermore identified several recently sequenced virus genomes (after 1 January 2014) that VirSorter did not and that have no nucleotide similarity to previously sequenced viruses, demonstrating VirFinder's potential advantage in identifying novel viral sequences. Application of VirFinder to a set of human gut metagenomes from healthy and liver cirrhosis patients reveals higher viral diversity in healthy individuals than cirrhosis patients. We also identified contig bins containing crAssphage-like contigs with higher abundance in healthy patients and a putative Veillonella genus prophage associated with cirrhosis patients.This innovative k-mer based tool complements gene-based approaches and will significantly improve prokaryotic viral sequence identification, especially for metagenomic-based studies of viral ecology.

Dataset Information

Libra: scalable k-mer-based tool for massive all-vs-all metagenome comparisons.

Publications

Libra: scalable k-mer-based tool for massive all-vs-all metagenome comparisons.

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