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BioNano Genomics



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BioNano Genomics

See Whole Genomes More Completely Than Ever

The Irys System from BioNano Genomics

BioNano Genomics introduces a more complete way of looking at DNA and chromosomes. With our revolutionary Irys genome mapping platform and NanoChannel technology, you can conduct unique studies to gain a comprehensive picture of genome biology, including structural variation.

The Irys System allows you to visualize whole genomes of any organism, including humans. By capturing extremely long molecules at high resolution, Irys delivers genome maps that allow you to:

  • Gain novel insight into structural variation that underlies phenotypic variation.
  • Achieve more complete assemblies, faster, using a comprehensive view of the whole genome for de novo assembly and finishing.
  • Unlock true genome biology with a range of applications that leverage single-molecule imaging that retains genomic architecture and context.

Avoid the hassle and bias of amplification or shearing and dissect complex mixtures at a single-molecule level, rather than losing rare variants in an averaged measurement. The cost-effective, high-throughput Irys system precisely characterizes genomic events in context of the entire genome, for more complete understanding.




WHY BUILD A BETTER GENOME MAP?

Traditionally, generating a whole-genome physical or genetic map has been one of the first steps in exploring genomes. Long-range information is crucial to the accurate understanding of relationships between functional elements in the genome and making sense of more detailed follow-on experiments.

Many current high-throughput genomic technologies start by fragmenting and amplifying DNA. This necessity often sacrifices vital long-range connectivity, causing researchers to miss many structural variants, including rearrangements, inversions and copy-number variants, which lead to inaccurately sized gaps.

Genome maps can contribute greatly to improving contiguity, accurately identifying gaps and revealing missed structural variation, even after a substantial amount of sequencing has been conducted. To achieve higher-quality genome analysis and comprehensive views of variation, a complete genome map is essential.

A Better Way to View the Genome

Traditional map-building methods are prohibitively expensive and time-consuming for use in all but reference genome projects. BioNano developed the Irys System to overcome these limitations and enable any lab to efficiently and cost-effectively further its research by creating genome maps of any organism under study.

The Irys System makes this possible by leveraging advances in nanoscale materials engineering, rather than relying on imprecise and low-throughput biological methods such as cloning and PCR. By linearizing and uniformly stretching extremely long pieces of DNA in NanoChannel arrays, the proprietary IrysChips preserve the true architecture of the genome. Genome maps are generated from massively parallel, single-molecule visualization of extremely long DNA without amplification, providing long-range contiguity and eliminating PCR bias.

DNA molecules labeled with IrysPrep reagents contain sufficient sequence-uniqueness to unambiguously map to a reference or assemble de novo. The result is a comprehensive, accurate, unbiased view that provides unique insights into genome structure and opens the door to countless applications, both with and without sequencing.


TECHNOLOGY

BioNano Genomics Irys workflow

Sample Prep and Labeling

IrysPrep kits provide all the reagents needed to label your DNA at specific sequence motifs for imaging and identification in IrysChips. There are a variety of techniques that are useful for labeling DNA. Some are based on enzymatic reactions; others are based on labeling with sequence-specific small molecules. A preferred method we are making available uses a nicking endonuclease to create a single-strand cut in the long DNA molecules at a specific recognition site, wherever it occurs in the genome. Fluorescently labeled nucleotides are then incorporated by repairing the single-strand nicks with a polymerase.

These labeling steps result in a uniquely identifiable sequence-specific pattern of labels to be used for de novo map assembly or for anchoring sequencing contigs. We anticipate commercialization of kits using other labeling techniques in the future.

Linearization and Imaging

A labeled DNA sample is pipetted onto the IrysChip in one or both flowcells. The Irys System controls the movement of DNA in the flowcell electrophoretically. A gradient of micro- and nano-structures, upstream of the IrysChip's NanoChannels, unravels DNA in solution and overcomes the entropic barrier to confine chromosomal-length nucleic acids inside the NanoChannels.

The current is transiently turned off and the molecules in solution are stationary and stretched uniformly. At this point imaging occurs, capturing high-resolution, single-molecule images of the labeled DNA that contains sequence motifs along hundreds of kilobases to longer than a megabase, in a single contiguous molecule. Once imaged, the molecules are flushed and the process is repeated, allowing imaging of several gigabases of DNA per hour.

The nanofluidic environment allows molecules to move swiftly through thousands of parallel channels simultaneously, enabling high-throughput processing to build a more accurate genome map.

This approach reveals meaningful biological information that is often disrupted or completely lost when molecules are sheared, including:

  • Architecture of the order and arrangement of functional regions, 
despite the presence of repetitive elements that confound other technologies
  • Context precisely outlining the relationships between elements
  • Interactions among individual or collections of genome elements
 by direct measurement rather than inference
  • Epigenetic modifications occurring across the genome

De Novo Genome Map Assembly

Raw image data of labeled long DNA molecules are converted to digital representations of the motif-specific label pattern. These data are then assembled de novo using IrysView data analysis software to recreate a whole genome consensus map of the original genome. Having a genome map in hand enables a variety of analyses, including sequence finishing and structural variation detection.


IRYS GENOME MAPS

Uses of a Genome Map

Retaining long-range contiguity throughout the genome mapping process is critical for any comprehensive study of genome structure and function, in particular de novo sequence scaffolding and analysis of structural variation in complex genomes. These maps provide dense genome-wide anchor points for ordering and orienting sequencing contigs or scaffolds to greatly increase completion and accuracy of de novo assemblies. Structural variants and repeats are measured directly within long, single-molecule "reads" for comprehensive analysis of what has been dubbed "the inaccessible genome."

Irys Genome Map without Sequencing

If an experiment doesn't call for single-base resolution, Irys Genome Maps can be used alone to identify architecture and structural variation. Repeating elements (simple or complex) can be tracked throughout a genome map. Comparing two individuals' genome maps, or an individual to a reference, will highlight structural and copy number variation. Positional information retained by long-range contiguity permits accurate quantitation of amplifications, detection of inversions, balanced translocations and the insertion location of duplications. Alternatively, Irys Genome Maps combined with sequencing data provide a powerful view of the genome at large to small scale.

Empowering Platform For User-Defined Applications

In addition to applications supported by IrysPrep reagents, the Irys System is an open platform designed to enable researchers to pursue other forms of genetic analysis. Myriad specialized applications that incorporate a fluorescent labeling method and benefit from long-range single-molecule measurement can be developed on the Irys System.


PRODUCTS

IRYS INSTRUMENT

BioNano Genomics IrysAcquire high-resolution, multi-color images and conduct single-molecule analysis of long DNA molecules with the automated, benchtop Irys Instrument. Simply load your sample, set your run on the touch-screen controls, and walk away as the system automatically flows DNA into the massively parallel array of NanoChannels on an IrysChip, collecting images and extracting data. By repeatedly cycling the same DNA sample through the same flowcell, the Irys Instrument can process several gigabases of DNA per hour.

Unamplified, native-state DNA molecules, each hundreds of kilobases long up to longer than a megabase, can be loaded into the IrysChip's NanoChannels. The Irys Instrument uses laser excitation to illuminate fluorescently labeled DNA in the NanoChannels of the chip. The DNA can be labeled using a wide variety of methods, including IrysPrep reagents or user-defined methods. An onboard CCD camera, coupled with proprietary auto-focusing mechanism and control software, rapidly scans the chip. Molecules are uniformly stretched and optically separated in NanoChannels, presenting high-resolution imaging of single molecules without extreme conditions and optics that make other platforms impractical and cost-prohibitive.

The Irys Instrument's control software makes processing samples effortless. Simply set up a run on the intuitive touchscreen and let the built-in software do the rest. The software automatically generates primary data for use in a number of applications. During a run, quality control metrics are constantly monitored and displayed on the screen, keeping you informed of the run's progress and success.

IRYSCHIPS

BioNano Genomics IrysChipThe key to generating useful genome maps is precise, long-range measurement of labels across thousands of bases to whole chromosomes. DNA is an inherently flexible molecule that naturally forms coils in solution, hindering accurate direct measurement. Only by using the IrysChip can you overcome this difficulty by linearizing the DNA within the proprietary NanoChannel arrays. These NanoChannels impart a highly uniform stretch and prevent molecules from folding or overlapping other molecules.

You can generate single-molecule data and create a comprehensive genome map from as little as 300 ng of labeled DNA using our IrysChips. Manufactured in a state-of-the-art semiconductor facility that ensures highly reproducible measurements, IrysChips are designed for efficient sample handling of precious or minute samples in a convenient 2-flowcell format. Choose to use one or both flowcells at a time, depending on your data needs. Each flowcell contains an array of NanoChannels long enough to contain intact megabase-length DNA molecules.

Bionano Genomics Irys Chip v2

After the DNA is imaged in the NanoChannels using the Irys Instrument, the molecules are flushed and a new batch of molecules is brought in. This dynamic, multi-cycle feature of Irys allows for high-throughput linearization and imaging of several gigabases of DNA per hour.

Ordering Information
For assistance in determining the correct quantity of IrysChips and IrysPrep Reagents for your genome, contact us for a project estimate

IRYSPREP REAGENTS

BioNano Genomics IrysPrep reagentsCreating a genome map starts with labeling long DNA molecules at specific sequence motifs to generate a unique pattern. IrysPrep reagent kits supplement readily available enzymes, with all the enzymes, dyes and buffers you need to label non-amplified DNA for the Irys system. Controls for validating the labeling biochemistry are also provided.

Ordering Information
For assistance in determining the correct quantity of IrysChips and IrysPrep Reagents for your genome, contact us for a project estimate

IRYSVIEW SOFTWARE

The powerful IrysView software integrates a host of specially designed algorithms that use the unique Irys data type to perform de novo assembly, alignment and variation detection. In addition, IrysView enables you to easily perform secondary data analysis on a separate workstation and offload large-genome assembly to a cluster. Assemble a genome map de novo, then compare it to other genome maps or imported sequences to conduct a variety of applications, including:BioNano Genomics IrysView software

  • Genome finishing - import NGS contigs to order and orient them, using your genome map to provide essential scaffolding information and precisely define gaps.
  • Assembly validation - compare sequencing contigs or scaffolds against your genome map for orthogonal validation and to identify misassemblies.
  • Structural variation detection - import a reference sequence to identify structural variation in your sample, which are displayed on the genome browser or a table that you can sort and export.
  • Comparative genomics - visualize variation between two different genome maps to find structural variation or differences in gene content and architecture.

All the data Irys generates are readily available to support any application. Export open file formats at any step in the pipeline for custom analysis, and easily dive down from a consensus map in the genome viewer to see the individual single-molecule images that were assembled.


LITERATURE

BIONANO GENOMICS IRYS SYSTEM DATASHEET

Product description and explanation of the benefits of incorporating the Irys System into your lab to expand your research. Example results include human structural variation, scaffolding, and using long molecules to bridge across highly repetitive regions.

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PUBLICATIONS

Download the latest publication list to see how other reasearchers are using the Irys genome mapping system.

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