• Application

  • Implementation

Publications

CSH Molecular Case Studies 2020
Ng J et al
Molecular and Cellular Endocrinology 2018
Barseghyan H et al
Genome Research 2017
McCaffrey J et al
Genome Research (2014); 24: 2066-2076 
Steinberg, K. et al.
BioMed Central Genomics (2014); 15(July 2014): 387 
O’Bleness, M., et al.

Videos

Unraveling complex structural variant patterns in cancer using optical mapping...
Towards high quality reference assemblies for all vertebrate genomes
Bionano data solutions to power your next discovery
Identifying structure of human papillomavirus genomes in head and neck...
Bionano optical mapping, in combination with other sequencing-based technologies, to...
Reference quality genomes of bats to illuminate the genomic determinants...
Improvements of North American catfish genome assemblies with optical mapping.
Recent workflow advances from Bionano Genomics
Genomic insights revealed by optical mapping the 3q29 deletion interval
Uncovering the precise genomic location of inversion events using optical...
Going beyond a single human reference. Lessons learned from sequencing...
Applications of whole genome imaging in translational research
Making the right call for structural variants interpretation using artificial...
Bionano mapping for evaluation of structural variants in genetic diseases
Optical mapping for chromosomal abnormalities. A pilot study for feasibility...
Characterization of clinically relevant repeats in the human genome
A novel molecular diagnostic tool for comprehensive assessment of structural...
Whole genome imaging to streamline cancer cytogenetics and identify novel...
High resolution view of D4Z4 repeat regions for studying FSHD...
Advanced analysis of risk loci in congenital disorders using Bionano...
Resolving complex genomic haplotypes in neurodegenerative disorders using Bionano Genomics...
Dr. Sven Bocklandt details the Saphyr Genome Imaging System's SV...
Dr. Hoischen reviews his work using Bionano digital cytogenetics applications
Dr. Kanagal-Shamanna shares how Saphyr technology detected novel structural variants...
Dr. Brynn Levy shares how Saphyr technology accurately detected clinical...
Overview of Bionano’s whole genome imaging technology.
Dr. Hastie reviews Bionano Saphyr's genome assembly capabilities at the...
Dr. Bocklandt reviews new developments in Bionano optical mapping and...
Dr. El Khattabi discusses Saphyr's ability to detect balanced and...
Dr. Hoischen discusses the assessment of Bionano Saphyr as a...

Webinars

Augusta University
Nikhil S. Sahajpal, PhD.

Nikhil S. Sahajpal, PhD, Augusta University – Presentation at the 2020 Cancer Genomics Consortium virtual meeting on whole genome optical mapping as a tool for next-generation cytogenomics.

Mayo Clinic
Dr. Mark T. W. Ebbert

Alzheimer’s disease is genetically complex with no meaningful therapies or pre-symptomatic disease diagnostics. Most of the genes implicated in Alzheimer’s disease do not have a known functional mutation, meaning there are no known molecular mechanisms to help understand disease etiology.

In this webinar, Mark T. W. Ebbert of the Mayo Clinic will discuss his team’s work toward identifying functional structural mutations that drive disease in order to facilitate a meaningful therapy and pre-symptomatic disease diagnostic.

Some of the genes and regions implicated in Alzheimer’s disease are genomically complex and cannot be resolved with short-read sequencing technologies. These regions include MAPT, CR1, and the histocompatibility complex (including the HLA genes).

Dr. Ebbert will share now the Saphyr system from Bionano Genomics resolves full haplotypes for these complex Alzheimer’s disease regions, as well as regions directly involved in other diseases, including amyotrophic lateral sclerosis (ALS), frontotemporal dementia (FTD), and Parkinson’s disease.

August 26, 2020 at 8:00A PDT | 11:00A EDT | 5:00P CET
If you are unable to attend the webinar, register to receive the recorded version for viewing at a later time.
Radboud Medical Center, Nijmegen, The Netherlands
Alexander Hoischen, PhD

Cytogenetics with 500,000 “bands”

~ 10,000 Improved Sensitivity!

  • Genomewide analysis
  • Positional information
  • Single molecule resolution
Children's National Medical Center
Dr. Hayk Barseghyan

You have a lot of great genomics data – so, what’s next?

In this webinar, we will explore tools and methods to analyze structural variation and demonstrate how to cut through the noise.

Genome imaging with Bionano’s Saphyr generates high quality structural variation calls for less than $500 per sample, with up to 99% sensitivity and with the lowest false positives. But getting great quality SV calls is only the first step. Dr. Hayk Barseghyan, Assistant Professor and researcher at Children’s National Medical Center, is arguably Bionano’s most experienced human genetics researcher, having analyzed hundreds of genomes of patients with a variety of undiagnosed genetic disorders and their parents. In this webinar, he will demonstrate how to filter thousands of structural variants down to the likely pathogenic ones, using three different tool sets:

  • Bionano’s own Access Software, and its Variant Annotation Pipeline
  • NanotatoR, open-source software for the annotation of structural variants developed by his team at Children’s National
  • The Genoox integrated pipeline, subscription software capable of integrating NGS reads with Bionano SV calls, which uses AI to annotate and classify point mutations and SVs
University of California, San Diego
Dr. Vineet Bafna

Oncogene amplification, a major driver of cancer pathogenicity, is often mediated through focal amplification of genomic segments. Recent results implicate extrachromosomal DNA (ecDNA) as the primary driver of focal copy number amplification (fCNA) – enabling gene amplification, rapid tumor evolution, and the rewiring of regulatory circuitry. Resolving an fCNA’s structure is a first step in deciphering the mechanisms of its genesis and the fCNA’s subsequent biological consequences. Here, we introduce a powerful new computational method, AmpliconReconstructor (AR), for integrating optical mapping (OM) of long DNA fragments (>150kb) with next-generation sequencing (NGS) to resolve fCNAs at single-nucleotide resolution. AR uses an NGS-derived breakpoint graph alongside OM scaffolds to produce high-fidelity reconstructions. After validating its performance by extensive simulations, we used AR to reconstruct fCNAs in seven cancer cell lines to reveal the complex architecture of ecDNA, breakage-fusion-bridge cycles, and other complex rearrangements. By distinguishing between chromosomal and extrachromosomal origins, and by reconstructing the rearrangement signatures associated with a given fCNA’s generative mechanism, AR enables a more thorough understanding of the origins of fCNAs, and their functional consequences.

Virtual Genetics Week 2020
Dr. Sven Bocklandt

The diagnostic yield in genetic disease has seen very little improvement over the last few decades, despite the introduction of whole genome sequencing.

The Bionano Genomics platform for genome imaging offers an extremely long-read technology, providing unmatched sensitivity and specificity to detect structural variation, genome-wide, at low cost. Our de novo maps can resolve complex repetitive regions, identify Copy Number Variations, and elucidate genome-wide structural variation like balanced/unbalanced translocations, inversions, and indels with much higher sensitivity and precision than sequencing-based methods.

For mosaic samples, Bionano’s high coverage depth allows for the detection of any type of structural variant with more than 90% sensitivity, present in as little as 10% of the cells, genome wide, and completely unbiased. Examples will be presented of how Bionano’s platform is helping solve genetic mysteries for patients with a variety of genetic disorders by detecting genomic rearrangements and structural variants missed by NGS and cytogenetic methods.

Paris Descartes University / Radboud Medical Center
Laila El Khattabi, PharmD PhD | Alexander Hoischen, PhD

Structural variants (SVs) are an important source of genetic variation in the human genome and they are involved in a multitude of human diseases as well as cancer. SVs are enriched in repeat-rich regions of the human genome, and several remain undetected by conventional short-read sequencing technologies. Here we applied Bionano Genomics’ high-resolution optical mapping to comprehensively identify SVs, leveraging the most recent improvements: a) deep-genome coverage (400x) to enable somatic mutation detection in leukemia samples; b) highest resolution (≥500bp) and no sequencing bias allows detection of SVs refractory to sequencing in rare disease cases.

Deep-genome coverage was used to comprehensively detect somatic SVs on 52 leukemia samples, and allowed the 100% concordance for all aberrations with >10% variant allele fraction that previously required a combination of karyotyping, FISH and/or CNV-microarray. In addition, optical mapping allowed the identification of SVs that remained refractory to detection by classical methods including MLPA, Sanger sequencing, exome and/or genome sequencing. This allowed the identification of likely disease causing SVs in 5/20 research cases. Including a) a partial deletion of the NSF gene located in the distal segmental-duplication in 17q21.31, which likely disrupts NSF in a patients with intellectual disability; this event remained undetected even by long-read SMRT sequencing; b) a retrotransposon insertion in patient with a tumor-predisposition syndrome.

In summary, the full concordance with diagnostic standard assays in leukemia demonstrates the potential to replace classical cytogenetic tests. We furthermore show how the complementary use of mapping rather than sequencing approaches can unmask hidden structural variants.

Penn State Health
Dr. Brandon LaBarge

Whole genome imaging using the Saphyr instrument from Bionano detects structural variants (SVs), such as insertions, deletions, and translocations, not readily evident from standard methods of whole genome analysis. This technology is particularly useful for detecting large (>500bp) and complex SVs that are difficult to detect using traditional short read sequencing alone. We have isolated high-molecular weight DNA (>150,000 bp) from various solid head and neck tumors using a protocol using a nanobind disc, consisting of novel nano structured silica surrounding a thermoplastic paramagnetic disk. This DNA is bar-coded using a direct labeling enzyme at a 6 bp consensus sequence scattered throughout the human genome. Cancer genome maps are assembled de novo based on label overlap and subsequently compared to a labeled human reference genome to identify SVs. We have successfully applied this framework to various head and neck solid tumors, including Human Papillomavirus (HPV)-positive oropharyngeal cancer, tongue cancer, and thyroid cancer. Genome imaging with whole genome sequencing can identify HPV insertion sites into the human genome of oropharyngeal cancers, and we have found viral integration to be associated with high genomic instability and more advanced clinical disease. Anaplastic thyroid cancer is a particularly aggressive form of cancer with strong genetic drivers in cell cycle regulation that can be described using the genome imaging platform. Short read sequencing in the literature has been inconclusive regarding the genetic difference between young and elderly tongue cancer, but genome imaging is able to detect different SVs affecting Ras signaling and the cell cycle between the two cohorts.

Accurate analysis of structural variants begins with isolating ultra-high molecular weight DNA. Obtaining high-quality UHMW DNA can present a challenge since sample collection, preservation, the DNA isolation process and subsequent handling of isolated DNA can significantly affect its quality.

In this webinar, Dr. Ben Clifford, Sr. Application Scientist at Bionano Genomics, discusses tips and tricks for isolating high quality UHMW DNA – right from sample collection, preservation and gentle handling of isolated DNA to minimize shearing and fragmentation.

In addition, we heard from Dr. Sven Bocklandt, Director of Scientific affairs at Bionano Genomics to walk us through genome imaging technology and workflow to demonstrate how it has been used successfully in studying structural variations in cancer and genetic diseases.

Cordelier Research Center - Paris
Dr. Eric Letouzé

“Bionano’s optical mapping technology allowed us to characterize complex structural rearrangements in cancer with unprecedented precision. The results are incredibly robust and easy to interpret with Bionano software, and the team was really helpful for data analysis!”
-Dr. Eric Letouzé

Cyclins A2 and E1 regulate the cell cycle by promoting S phase entry and progression. We recently identified a hepatocellular carcinoma (HCC) subgroup exhibiting cyclin activation through various mechanisms, including HBV and AAV2 viral insertions, gene fusions and enhancer hijacking. Those poor-prognosis HCCs display a unique signature of structural rearrangements, triggered by replicative stress. This signature is strongly enriched in early-replicated active chromatin regions and is characterized by hundreds of tandem duplications and more complex events called Templated Insertion Cycle (T.I.C.).

Structural variation calling from short-read Whole Genome Sequencing provides abnormal junctions by comparing chimeric reads with a reference genome. However, those independent breakpoints are too distant, thus this method is not enough to reconstruct highly complex rearrangements, which may involve up to dozens of regions of the genome linked together. Here we used Bionano data to characterize with certainty large DNA molecules resulting from complex T.I.C.. This analysis allowed us to know which regions of the genome are the acceptor of such complex structural rearrangements. This information is critical in the understanding of how those rearrangements affect genes involved in tumorigenesis by placing oncogenes in different genomic contexts.

Sanford Burnham Prebys Medical Discovery Institute
Dr. Darren "Ben" Finlay & Dr. Rabi Murad
Bionano Genomics
Dr. Sven Bocklandt

Accumulation of structural variations (SVs) across the genome is a known trigger factor for oncogenesis. Identifying these structural genomic alterations – accurately and comprehensively – is crucial for improving research and ultimately therapies for cancer patients, yet one of primary challenges when solely relied on short read sequencing and standard cytogenetic methods (e.g. karyotyping, FISH and chromosomal microarrays).

Optical mapping with genome imaging, enabled by the Bionano Saphyr® System, can accurately assemble and assay relevant regions for complex genomic disorders like cancer, even those involving very large segmental duplications. Genome imaging has to date unraveled a number of genes, never implicated in cancer and shown how they are affected by structural variations, along with deciphering novel structural variants. Listen to this webinar to learn how combining genome imaging with whole genome sequencing offers a strong integrative approach to understand small and large genomic variations in cancers.

Radbound Medical Center
Dr. Alexander Hoischen, Associate Professor, Genomic Technologies & Immuno-genomics

This webinar outlines how a team at Radboud University Medical Center is assessing ultra-long read optical mapping on the Bionano Saphyr System to replace classical cytogenetics approaches in routine testing and for the discovery of novel structural variants with potential scientific, prognostic, or therapeutic value that are missed by standard approaches.

Vanessa Hayes
Garvan Institute of Medical Research
Dr. Vanessa Hayes, PhD
Eric Vilain
Chief of Medical Genetics at UCLA
Dr. Eric Vilain, MD, PhD
Alex Harkess
Donald Danforth Plant Science Center
Alex Harkess
Florian Jupe
Salk Institute of Biological Studies
Florian Jupe
Wellcome Trust Sanger Institute
William Chow
Kansas State University
Dr. Sue Brown
Wageningen University
Dr. Gabino Sanchez Perez
Icahn School of Medicine at Mount Sinai
Dr. Ali Bashir and Dr. Bobby Sebra
The Genome Institute at Washington University
Tina Graves
Institute of Experimental Botany, Olomouc
Dr. Jaroslav Dolezel
Emory University
Dr. Michael Rossi

Posters

February, 2020
AGBT 2020, Marco Island, Florida
February, 2018
Advances in Genome Biology and Technology, Orlando, Fl
February, 2018
Advances in Genome Biology and Technology, Orlando, Fl
May, 2017
European Society of Human Genetics Annual Meeting, Copenhagen, Denmark
May, 2017
European Society of Human Genetics Annual Meeting, Copenhagen, Denmark
March, 2017
ACMG Annual Clinical Genetics Meeting, Phoenix, Arizona
February, 2017
Advances in Genome Biology and Technology 2017 General Meeting, Hollywood, FL
February, 2017
Advances in Genome Biology and Technology 2017 General Meeting, Hollywood, FL
January, 2017
Plant and Animal Genome Conference XXV, San Diego, CA
January, 2017
Plant and Animal Genome Conference XXV, San Diego, CA
October, 2016
American Society of Human Genetics, San Diego, CA
March, 2016
Annual Clinical Genetics Meeting, Tampa, FL
February, 2016
Advances in Genome Biology and Technology, Orlando, FL
February, 2016
Advances in Genome Biology and Technology, Orlando, FL
January, 2016
Plant and Animal Genome Conference XVII, San Diego, CA
January, 2016
Plant and Animal Genome Conference XVII, San Diego, CA
January, 2016
Plant and Animal Genome Conference XVII, San Diego, CA
January, 2016
Plant and Animal Genome Conference XVII, San Diego, CA
January, 2016
Plant and Animal Genome Conference XVII, San Diego, CA
October, 2015
American Society of Human Genetics, Baltimore, MD
October, 2015
American Society of Human Genetics, Baltimore, MD
October, 2015
American Society of Human Genetics, Baltimore, MD
October, 2015
American Society of Human Genetics, Baltimore, MD
October, 2015
American Society of Human Genetics, Baltimore, MD
May 2015 / June 2015
Biology of Genomes / European Society of Human Genetics, Cold Spring Harbor, NY (USA) / Glasgow (UK)
May 2015 / June 2015
Biology of Genomes / European Society of Human Genetics, Cold Spring Harbor, NY (USA) / Glasgow (UK)
May 2015 / June 2015
Biology of Genomes / European Society of Human Genetics, Cold Spring Harbor, NY (USA) / Glasgow (UK)
April 2015 / June 2015
American Association for Cancer Research / European Society of Human Genetics, Philadelphia, PA (USA) / Glasgow (UK)
February, 2015
Advances in Genome Biology and Technology, Marco Island, FL
February, 2015
Advances in Genome Biology and Technology, Marco Island, FL
February, 2015
Advances in Genome Biology and Technology, Marco Island, FL
January, 2015
Plant and Animal Genome XXIII, San Diego, CA
January, 2015
Plant and Animal Genome XXIII, San Diego, CA
January, 2015
Plant and Animal Genome XXIII, San Diego, CA
November, 2014
Precision Medicine: Personal Genomes & Pharmacogenomics, Cold Spring Harbor, NY
October, 2014
Beyond the Genome, Boston, MA
October, 2014
American Society of Human Genetics, San Diego, CA
October, 2014
American Society of Human Genetics, San Diego, CA
October, 2014
American Society of Human Genetics, San Diego, CA
October, 2014
American Society of Human Genetics, San Diego, CA
September, 2014
Human Genome Variation, Belfast, Ireland
June, 2014
European Society of Human Genetics, Milan, Italy
June, 2014
European Society of Human Genetics, Milan, Italy
May, 2014
Sequencing, Finishing, Analysis in the Future, Santa Fe, NM
May, 2014
Sequencing, Finishing, Analysis in the Future, Santa Fe, NM
February, 2014
Advances in Genome Biology and Technology, Marco Island, FL
January, 2014
Plant and Animal Genome Conference XVII, San Diego, CA
November, 2013
Precision Medicine: Personal Genomes & Pharmacogenomics, Cold Spring Harbor, NY
January, 2013
Plant and Animal Genome Conference XXI, San Diego, CA
November, 2012
American Society of Human Genetics, San Francisco, CA

Literature

white papers

This white paper is based on a webinar presentation by Alexander Hoischen of Radboud University Medical Center, in which he discussed the promise of genome imaging technology for medical genetics.

Dr. Hoischen shared details of a proof-of-concept study his lab is conducting to evaluate the Saphyr whole genome imaging technology from Bionano Genomics as a possible replacement for karyotyping, fluorescent in situ hybridization, and copy number variant microarrays.

white papers

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 Imaging is able to detect all SV types with high sensitivity and specificity, and examples of cancer and genetic disease are shown.

white papers

This white paper is based on a webinar presentation by Dr. James Broach of the Penn State College of Medicine. He discussed methods for capturing a comprehensive snapshot of all variants—both point mutations and structural variants—present in a tumor sample in order to gain insights about the genetic and genomic basis of individual cancers.

white papers

Bionano whole genome imaging 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.

white papers

This white paper explains how Bionano whole genome imaging can make any sequence assembly up to 100 times more contiguous by scaffolding sequence contigs, and more exact by correcting errors. The new two-enzyme hybrid scaffold pipeline introduced here improves both aspects. It creates functional genomes at a low cost, no matter what your sequencing strategy is.

case studies

This Case Study demonstrates the power of combining 2 single molecule technologies to produce Gold-quality genomes. Those allow the discovery of substantial amount of structural variation unique to individuals and populations otherwise not accessed by other short-read technologies.

case studies

This Case Study highlights Scientists at the USDA and Cold Spring Harbor Laboratory who know that better breeding of maize to feed a growing population will depend on an accurate reference assembly. They tackled the previously intractable crop with a combination of PacBio® Sequencing and BioNano Genomics®genome maps, leading to the first-ever high-quality reference assembly.

case studies

Scientists at Rutgers University, Washington University, and Ibis Biosciences successfully deployed Next-Generation Mapping (NGM) technology from Bionano Genomics to help produce the first complete assembly for a fast-growing aquatic plant with biofuel potential. What emerged is a clear view into a genome undergoing drastic reduction and a tool to elucidate chromosome-scale dynamics.