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 500 bp to megabase pair lengths.

  • 99% sensitivity for homozygous insertions/deletions larger than 500 base pairs
  • 95% sensitivity for heterozygous insertions/deletions larger than 500 base pairs
  • 95% sensitivity for balanced and unbalanced translocations larger than 50,000 base pairs
  • 99% sensitivity for inversions larger than 30,000 base pairs
  • 97% sensitivity for duplications larger than 30,000 base pairs
  • 97% sensitivity for copy number variants larger than 500,000 base pairs

For mosaic samples or heterogeneous cancer samples, Saphyr detects all types of structural variants down to 5% Variant Allele Fraction. Saphyr provides this performance typically with a false positive rate of less than 2%. Saphyr also calls repeats 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 hundreds of times more contiguous assembly than sequencing technologies alone can provide.

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


Dr. Sven Bocklandt
Dr. Bocklandt reviews new developments in Bionano optical mapping and novel applications for cancer and genetic disease
Dr. Laïla El Khattabi
Dr. El Khattabi discusses Saphyr's ability to detect balanced and unbalanced structural variants
Dr. Alexander Hoischen
Dr. Hoischen discusses the assessment of Bionano Saphyr as a replacement for FISH, karyotyping and CNV arrays


      White Papers
    • Bionano optical genome mapping is the only technology that allows for the highly sensitive detection of all structural variant types present at low allele fraction in heterogenous cancer samples, in an unbiased genome-wide manner. By providing a complete and unambiguous picture of the cancer genome structure, it can identify prognostic markers not currently monitored, and enable a complete characterization of the cancer genome in single test, potentially replacing multiple cytogenetic tests that make up the gold standard.

    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.

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