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Related Experiment Video

Updated: Apr 12, 2026

Hybrid De Novo Genome Assembly for the Generation of Complete Genomes of Urinary Bacteria using Short- and Long-read Sequencing Technologies
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Assembling large genomes with single-molecule sequencing and locality-sensitive hashing.

Konstantin Berlin1, Sergey Koren2, Chen-Shan Chin3

  • 11] Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland, USA. [2] Institute for Advanced Computer Studies, University of Maryland, College Park, Maryland, USA. [3] Invincea Labs, Arlington, Virginia, USA.

Nature Biotechnology
|May 26, 2015
PubMed
Summary
This summary is machine-generated.

We developed the MinHash Alignment Process (MHAP) to assemble long, noisy DNA reads from single-molecule real-time (SMRT) sequencing. This method enables high-accuracy, near-complete eukaryotic genome assemblies, including previously uncharacterized sequences.

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Area of Science:

  • Genomics
  • Bioinformatics
  • Molecular Biology

Background:

  • Long-read sequencing technologies like single-molecule real-time (SMRT) sequencing are crucial for genome assembly.
  • Existing assembly algorithms struggle to scale effectively for large, complex eukaryotic genomes.
  • Closing gaps and resolving complex regions remain challenges in de novo genome assembly.

Purpose of the Study:

  • To introduce a novel algorithm, the MinHash Alignment Process (MHAP), for efficient and accurate assembly of long, noisy sequencing reads.
  • To demonstrate the capability of MHAP integrated with the Celera Assembler for generating reference-grade de novo eukaryotic genome assemblies.
  • To improve the contiguity and accuracy of genome assemblies, particularly in complex and repetitive genomic regions.

Main Methods:

  • Development of the MinHash Alignment Process (MHAP) utilizing probabilistic, locality-sensitive hashing for overlapping noisy, long reads.
  • Integration of MHAP with the Celera Assembler for de novo genome assembly.
  • Application of the combined method to SMRT sequencing data from Saccharomyces cerevisiae, Arabidopsis thaliana, Drosophila melanogaster, and a human cell line (CHM1).

Main Results:

  • Achieved reference-grade de novo assemblies for multiple eukaryotic organisms using SMRT sequencing data.
  • Generated highly continuous assemblies, including fully resolved chromosome arms and closed persistent gaps.
  • Discovered novel heterochromatic and telomeric transition sequences in D. melanogaster and filled gaps in the human GRCh38 reference genome with low-complexity sequences from CHM1.
  • Demonstrated high accuracy (99.99%) of the resulting assemblies when compared to existing reference genomes.

Conclusions:

  • MHAP combined with the Celera Assembler significantly advances the de novo assembly of large eukaryotic genomes from long-read sequencing data.
  • This approach enables the production of near-complete and highly accurate eukaryotic genome assemblies, revealing previously inaccessible genomic regions.
  • Single-molecule sequencing is now a viable method for generating high-quality, reference-grade eukaryotic genome assemblies.