Home LiteratureArticle Details
PMID: 22847406 Published · ppublish English Journal Article Research Support, U.S. Gov't, Non-P.H.S.

Scaling metagenome sequence assembly with probabilistic de Bruijn graphs.

Pell J, Hintze A, Canino-Koning R, Howe A, Tiedje JM, Brown CT

Abstract

Deep sequencing has enabled the investigation of a wide range of environmental microbial ecosystems, but the high memory requirements for de novo assembly of short-read shotgun sequencing data from these complex populations are an increasingly large practical barrier. Here we introduce a memory-efficient graph representation with which we can analyze the k-mer connectivity of metagenomic samples. The graph representation is based on a probabilistic data structure, a Bloom filter, that allows us to efficiently store assembly graphs in as little as 4 bits per k-mer, albeit inexactly. We show that this data structure accurately represents DNA assembly graphs in low memory. We apply this data structure to the problem of partitioning assembly graphs into components as a prelude to assembly, and show that this reduces the overall memory requirements for de novo assembly of metagenomes. On one soil metagenome assembly, this approach achieves a nearly 40-fold decrease in the maximum memory requirements for assembly. This probabilistic graph representation is a significant theoretical advance in storing assembly graphs and also yields immediate leverage on metagenomic assembly.

MeSH Terms
Base Pairing/genetics Chromosomes, Bacterial/genetics Computational Biology DNA, Circular/genetics Escherichia coli/genetics Genome, Bacterial/genetics Information Theory Metagenome/genetics Nonlinear Dynamics Sequence Analysis, DNA/methods Soil Microbiology
Chemicals
DNA, Circular
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Pell Jason
Computer Science and Engineering, Michigan State University, East Lansing, MI 48824, USA.
Hintze Arend
Canino-Koning Rosangela
Howe Adina
Tiedje James M
Brown C Titus
References (29)
29 references, click to expand
  1. Computational improvements reveal great bacterial diversity and high metal toxicity in soil.
    Science. 2005 Aug 26;309(5739):1387-90 PMID: 16123304
  2. Efficient counting of k-mers in DNA sequences using a bloom filter.
    BMC Bioinformatics. 2011 Aug 10;12:333 PMID: 21831268
  3. A primer on metagenomics.
    PLoS Comput Biol. 2010 Feb 26;6(2):e1000667 PMID: 20195499
  4. Velvet: algorithms for de novo short read assembly using de Bruijn graphs.
    Genome Res. 2008 May;18(5):821-9 PMID: 18349386
  5. DNA sequence assembly and multiple sequence alignment by an Eulerian path approach.
    Cold Spring Harb Symp Quant Biol. 2003;68:205-12 PMID: 15338619
  6. Critical and near-critical branching processes.
    Phys Rev E Stat Nonlin Soft Matter Phys. 2002 Jul;66(1 Pt 1):011907 PMID: 12241384
  7. Genome assembly reborn: recent computational challenges.
    Brief Bioinform. 2009 Jul;10(4):354-66 PMID: 19482960
  8. Classification of DNA sequences using Bloom filters.
    Bioinformatics. 2010 Jul 1;26(13):1595-600 PMID: 20472541
  9. Environmental genome shotgun sequencing of the Sargasso Sea.
    Science. 2004 Apr 2;304(5667):66-74 PMID: 15001713
  10. Full-length transcriptome assembly from RNA-Seq data without a reference genome.
    Nat Biotechnol. 2011 May 15;29(7):644-52 PMID: 21572440
  11. Metagenomic discovery of biomass-degrading genes and genomes from cow rumen.
    Science. 2011 Jan 28;331(6016):463-7 PMID: 21273488
  12. De novo identification of repeat families in large genomes.
    Bioinformatics. 2005 Jun;21 Suppl 1:i351-8 PMID: 15961478
  13. A human gut microbial gene catalogue established by metagenomic sequencing.
    Nature. 2010 Mar 4;464(7285):59-65 PMID: 20203603
  14. Metagenomic analysis of a permafrost microbial community reveals a rapid response to thaw.
    Nature. 2011 Nov 06;480(7377):368-71 PMID: 22056985
  15. An Eulerian path approach to DNA fragment assembly.
    Proc Natl Acad Sci U S A. 2001 Aug 14;98(17):9748-53 PMID: 11504945
  16. Meta-IDBA: a de Novo assembler for metagenomic data.
    Bioinformatics. 2011 Jul 1;27(13):i94-101 PMID: 21685107
  17. MetaVelvet: an extension of Velvet assembler to de novo metagenome assembly from short sequence reads.
    Nucleic Acids Res. 2012 Nov 1;40(20):e155 PMID: 22821567
  18. A parallel algorithm for error correction in high-throughput short-read data on CUDA-enabled graphics hardware.
    J Comput Biol. 2010 Apr;17(4):603-15 PMID: 20426693
  19. Meeting report: the terabase metagenomics workshop and the vision of an Earth microbiome project.
    Stand Genomic Sci. 2010 Dec 25;3(3):243-8 PMID: 21304727
  20. High-quality draft assemblies of mammalian genomes from massively parallel sequence data.
    Proc Natl Acad Sci U S A. 2011 Jan 25;108(4):1513-8 PMID: 21187386
  21. Succinct data structures for assembling large genomes.
    Bioinformatics. 2011 Feb 15;27(4):479-86 PMID: 21245053
  22. DecGPU: distributed error correction on massively parallel graphics processing units using CUDA and MPI.
    BMC Bioinformatics. 2011 Mar 29;12:85 PMID: 21447171
  23. How to apply de Bruijn graphs to genome assembly.
    Nat Biotechnol. 2011 Nov 08;29(11):987-91 PMID: 22068540
  24. De novo assembly and genotyping of variants using colored de Bruijn graphs.
    Nat Genet. 2012 Jan 08;44(2):226-32 PMID: 22231483
  25. GAGE: A critical evaluation of genome assemblies and assembly algorithms.
    Genome Res. 2012 Mar;22(3):557-67 PMID: 22147368
  26. Quake: quality-aware detection and correction of sequencing errors.
    Genome Biol. 2010;11(11):R116 PMID: 21114842
  27. ABySS: a parallel assembler for short read sequence data.
    Genome Res. 2009 Jun;19(6):1117-23 PMID: 19251739
  28. Assembly algorithms for next-generation sequencing data.
    Genomics. 2010 Jun;95(6):315-27 PMID: 20211242
  29. The Earth Microbiome Project: Meeting report of the "1 EMP meeting on sample selection and acquisition" at Argonne National Laboratory October 6 2010.
    Stand Genomic Sci. 2010 Dec 25;3(3):249-53 PMID: 21304728
Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
1091-6490
Published
2012-08-14
Epub
2012-00-30
Pages
13272-7
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC3421212
Subset
IM
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com