Assembly and diploid architecture of an individual human genome via single-molecule technologies

Pendleton, M., Sebra, R., Pang, A. W., Ummat, A., Franzen, O., Rausch, T., Stutz, A. M., Stedman, W., Anantharaman, T., Hastie, A., Dai, H., Fritz, M. H., Cao, H., Cohain, A., Deikus, G., Durrett, R. E., Blanchard, S. C., Altman, R., Chin, C. S., Guo, Y., Paxinos, E. E., Korbel, J. O., Darnell, R. B., McCombie, W. R., Kwok, P. Y., Mason, C. E., Schadt, E. E., Bashir, A. (2015) Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nat Methods, 12 (8). pp. 780-786. ISSN 1548-7105 (Electronic)1548-7091 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/26121404
DOI: 10.1038/nmeth.3454

Abstract

We present the first comprehensive analysis of a diploid human genome that combines single-molecule sequencing with single-molecule genome maps. Our hybrid assembly markedly improves upon the contiguity observed from traditional shotgun sequencing approaches, with scaffold N50 values approaching 30 Mb, and we identified complex structural variants (SVs) missed by other high-throughput approaches. Furthermore, by combining Illumina short-read data with long reads, we phased both single-nucleotide variants and SVs, generating haplotypes with over 99% consistency with previous trio-based studies. Our work shows that it is now possible to integrate single-molecule and high-throughput sequence data to generate de novo assembled genomes that approach reference quality.

Item Type: Paper
Subjects: bioinformatics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > genomes
Investigative techniques and equipment > assays > next generation sequencing
CSHL Authors:
Communities: CSHL Cancer Center Program > Cancer Genetics
CSHL labs > McCombie lab
CSHL Cancer Center Shared Resources > DNA Sequencing Service
Depositing User: Matt Covey
Date Deposited: 01 Jul 2015 18:51
Last Modified: 04 Nov 2015 21:25
Related URLs:
URI: http://repository.cshl.edu/id/eprint/31605

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