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

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.

Related Video: 

Dr. Vanessa Hayes from the Garvan Institute talks about her work in human diversity and prostate cancer and shares how Bionano genome mapping helps us better understand disease.

“Large structural variations are important and it is our hope that they become the biomarkers that clinicians use to be able to decide how to treat and manage a patient.”

LEARN ABOUT SAPHYR

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

Publications

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Videos

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

Posters

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Literature

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      White Papers
    • Bionano Genome Mapping Identifies Large Structural Variants in Cancer and Genetic Disorders

      This White Paper explains how NGS leaves half of patients with genetic disorders without a molecular diagnosis, because it fails to adequately analyze repetitive parts of the genome and large structural variation. Bionano Genome Mapping is able to detect all SV types with high sensitivity and specificity, and examples of cancer and genetic disease are shown.

    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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