BioNano study describes use of Irys System with Illumina-based NGS methods to achieve high-quality genomic assemblies

Study Published in Nature Methods Describes Use of BioNano Irys^® with Illumina-Based NGS Methods

BioNano Genomics, the leader in physical genome mapping, today announced publication of another study describing application of its next-generation mapping (NGM) technology as the critical component in achieving high-quality de novo human genome assemblies with unprecedented contiguity. In the current study, researchers combined NGM with Illumina-based approaches for next-generation sequencing (NGS) and demonstrated that when the GemCode™ Technology from 10X Genomics is used for sequencing library preparation, the resulting hybrid assembly has comparable or slightly better contiguity to that of NGM-NGS hybrid assemblies achieved with PacBio in previous studies such as that of Pendleton and colleagues at Mt. Sinai published in a June 2015 issue of Nature Methods. The results of the new study were published online today in the article "A hybrid approach for de novo human genome sequence assembly and phasing" in the May 2016 issue of Nature Methods.

Pui-Yan Kwok, M.D., Ph.D., senior author of the article and the Henry Bachrach Distinguished Professor at the University of California, San Francisco, stated:

Genomic information derived from long-range technologies allows us to take discovery several steps beyond that based solely on single nucleotide polymorphisms (SNPs). Using BioNano’s Next-Generation Mapping solution in combination with medium-length contiguity information provided by newer sequencing methods, any researcher can produce highly contiguous de novo genome assembly of complex genomes. Our approach makes it possible to detect structural variations with base pair resolution across the genome in one set of experiments and open up the field for many new applications.

Dr. Pui Kwok and colleagues at University of California in San Francisco’s Cardiovascular Research Institute/Institute for Human Genetics and researchers at the University of Cape Town’s Department of Molecular and Cell Biology used BioNano’s Irys^® System to build physical maps of the genome in which long-range information spanning complex regions such as repeats and other structural variations is intact. They integrated the maps with sequence assemblies based on Illumina short-read sequencing and library preparation from 10X Genomics for linked-reads. This combination of NGM, linked-reads and Illumina-based sequencing, similar to the combination of PacBio sequencing and NGM, overcomes limitations of NGS alone. Here, the hybrid approach with BioNano led to a 57-fold increase in N50 scaffold length over Illumina generated N50 scaffolds and a 4.8-fold increase over the N50 of hybrids with only 10X Genomics’ linked-reads and Illumina NGS.  The authors pointed out how some 14.3 Mbp of the NA12878 genome, not represented in the hg38 reference genome, was identified and correctly located in the assembly. These findings underscore the limitations of a single reference genome and the importance of using NGM-NGS hybrid assemblies to build highly contiguous reference quality genomes on a population basis to minimize the findings of pseudo-variations that are associated with errors or limits of a given reference.

Erik Holmlin, Ph.D., President and Chief Executive Officer of BioNano Genomics, commented:

I’m pleased to see the growing use of NGM as a key tool in obtaining such high quality genome assemblies. The 10X approach makes it easier to integrate Illumina’s NGS together with NGM and expands the opportunity to create much better reference genomes.  Improving reference genomes will help applications of BioNano’s NGM as a stand-alone tool for discovery of novel, clinically and biologically relevant structural variations (SVs) as well as make NGM a more efficient approach to detecting those SVs already known for their clinical and translational applications.