Human Genome Research

The promise of genomics in relation to human disease is being held back by the inability to resolve large structural variations. Existing technologies, including next-generation sequencing (NGS), diagnose less than 50% of patients with genetic disorders.1,2 Bionano genome mapping offers unmatched structural variation discovery, making Saphyr™ essential to human genome and translational research.


Large structural variants such as deletions, duplications, inversions and translocations are extensively present, and many are known to affect biological functions and cause disease, including cancers and developmental disorders.

Precision medicine initiatives require accurate analyses of human genomes. While improvements in sequencing technology have allowed for spectacular progress in the detection of single nucleotide changes, the analysis of larger structural variations has remained ineffective. Standard methodologies for detecting structural variations have significant limitations. Chromosomal microarray is insensitive to novel insertions, mobile element insertions, many low copy repeats, and all balanced translocations and inversions. In addition, short-read sequencing methods have low sensitivity to most large variants and often fail in repetitive regions or those with high GC-content. Long-read sequencing has better sensitivity for heterozygous structural variations but is unable to span larger repetitive regions.

Saphyr fills in what’s missing from sequencing-based and other approaches with unparalleled sensitivity for large structural variations from 1,000 bp to megabase pair lengths.

  • 99% sensitivity for large homozygous insertions and deletions
  • 87% sensitivity for large heterozygous insertions and deletions
  • 98% sensitivity for translocations

Saphyr provides this performance with a false positive rate of less than 3%. Saphyr also calls inversions, repeats, copy number variants and complex rearrangements.

Unlike NGS, which algorithmically infers structural variants from fragmented DNA data, Bionano optical genome mapping directly observes structural variations by linearizing and imaging DNA in its native state using massively parallel NanoChannels. This direct observation results in some of the longest read lengths in genomic research. As a result, Bionano next-generation mapping yields up to 100 times more contiguous assembly than sequencing technologies alone can provide.

In fact, every recent human reference-quality genome published uses Bionano genome mapping data.3,4,5,6

See below for publications, white papers and other resources regarding Bionano genome mapping in human genome and translational research.

Use Cases

  • Undiagnosed Genetic Disorders – close the diagnosis gap by detecting large structural events missed by NGS
  • Gene discovery and therapy development – identify genes of interest, their locations and how structural variations impact them to inform effective therapy development
  • Cancer – detect and visualize large rearrangements occurring in cancer genomes
  • Cell line studies – monitor genomic integrity of cell lines and off-target effects of genetic engineering
  • Reference genome assembly – perform de novo assembly and correct assemblies generated by sequencing-based systems


University of California San Francisco, USA
Dr. Kwok discusses Bionano structural variant discovery in human diseases
Garvan Institute for Medical Research, Australia
Dr. Hayes discusses how Bionano aids her work prostate cancer


    1. Miller DT, A. M. (2010). Consensus statement: chromosomal microarray is a first-tier clinical diagnostic test for individuals with developmental disabilities or congenital anomalies. Am J Hum Genet, 86 (5), 749-64.
    2. Hane Lee, J. L.-R.-A. (2014). Clinical Exome Sequencing for Genetic Identification of Rare Mendelian Disorders. JAMA, 312 (18), 1880-1887.
    3. Pendleton, M., Sebra, R., et al. Assembly and diploid architecture of an individual human genome via single-molecule technologies. Nature Methods (2015); e3454.
    4. Zimin et al. Hybrid assembly of the large and highly repetitive genome of Aegilops tauschii, a progenitor of bread wheat, with the mega-reads algorithm bioRxiv. (2016).
    5. Shi et al. Long-read sequencing and de novo assembly of a Chinese genome. Nature Communications (2016). 
    6. Seo, JS, et al. De novo assembly and phasing of a Korean human genome. Nature (2016).

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