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Authors: Pendleton, Matthew and Sebra, Robert and Pang, Andy Wing Chun and Ummat, Ajay and Franzen, Oscar and Rausch, Tobias and Stütz, Adrian M and Stedman, William and Anantharaman, Thomas and Hastie, Alex and Dai, Heng and Fritz, Markus Hsi-Yang and Cao, Han and Cohain, Ariella and Deikus, Gintaras and Durrett, Russell E and Blanchard, Scott C and Altman, Roger and Chin, Chen-Shan and Guo, Yan and Paxinos, Ellen E and Korbel, Jan O and Darnell, Robert B and McCombie, W Richard and Kwok, Pui-Yan and Mason, Christopher E and Schadt, Eric E and Bashir, Ali

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.

Journal: Nature methods
DOI: 10.1038/nmeth.3454
Year: 2015

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