Application
Long String Genomics
The analysis of (ultra) long nucleic acid molecules, either by sequencing or structural assessment, herein collectively referred to as long string genomics, has substantial benefits over more traditional approaches.
Unlike with short-read sequencing or other applications, larger DNA or RNA molecules can be analyzed either by long-read sequencing or Optical Genome Mapping (OGM) to gain deeper insight with higher resolution into otherwise difficult-to-assess genetic variation.
These advancements will continue to unveil unresolved mysteries and drive new discoveries in human health and disease research, as well as in studies of other complex genomes.
Long-read sequencing, primarily offered by Pacific Biosciences (PacBio) and Oxford Nanopore Technologies, provides unbiased reads with lengths between 15-20 kbp to over 100 kbp. This enables improved (de novo) assembly and variant calling, especially in structurally complex or repetitive regions, along with providing haplotype and epigenetic information. Long-read RNA seq further expands capabilities to investigate different RNA species and features.
OGM uses optical images of enzymatically labeled Ultra High Molecular Weight (UHMW) DNA molecules. This method comprehensively detects all structural variant classes, covering resolutions from 500 bp to megabase pairs. This approach substantially surpasses standard cytogenetic methods while complementing short-read NGS.
How Hamilton Supports Your Long-String Genomics Workflows
Key workflow processes in long-read sequencing and optical genome mapping with Hamilton automation solutions.
Hamilton has partnered with leading kit manufacturers and technology providers to automate key processes within long-read sequencing and OGM workflows. Beyond standard DNA or RNA extraction using magnetic beads or silica membranes, this includes High Molecular Weight (HMW) DNA (50-250 kbp) extraction on the NIMBUS Presto. The subsequent downstream long-read sequencing library preparation, suitable for leading sequencing platforms, is automated on our different NGS Assay Ready Workstations for various throughput needs.
For Ultra High Molecular Weight (UHMW) DNA (250 up to ≥ 1Mbp) extraction, as well as the downstream enzymatic labeling process for full OGM workflow automation, is enabled on the Long String STAR V.
Explore our Long String Genomics Solutions and Applications in Detail
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Assay Ready Workstations
NGS STARlet
Compact and efficient, the entry-level NGS STARlet from Hamilton includes all the devices you need to automate sequencing library preparation of up to 24 samples at once with detailed precision, accuracy, and reliability.
Assay Ready Workstations
NGS STAR Line
Hamilton NGS STAR helps streamline next-generation sequencing in labs. Achieve full NGS automation for library prep, optimized for NGS assays and genome sequencing. Enhance efficiency, precision, and reliability in your workflows. Explore the Hamilton NGS STAR for seamless sequencing today!
Assay Ready Workstations
NGS STAR V
Automate NGS library preparation with the Hamilton NGS STAR V Assay Ready Workstation—optimized for demanding high-throughput genomic research.
The Hamilton Microlab Prep is an affordable liquid handler perfect for automating workflows. This entry-level liquid handler supports automated PCR setup and serial dilution.
Lab Syringes
Gastight Syringes
The solution for dispensing both gases and heterogeneous liquids. Hamilton Gastight syringes are equipped with a precision-machined PTFE plunger tip to create a leak-free seal.
Lab Syringes
Microliter Syringes
Hamilton Microliter syringes are ideal for dispensing homogeneous liquid samples not prone to glass bonding or precipitation. With a hand-fitted stainless steel plunger for frictionless movement and minimal wear, these syringes are designed to last.
Good to Know About Long String Genomics Workflows
This section provides a selection of additional resources related to the application described on this page. It includes helpful articles, videos, and blogs that offer deeper insights into the topic.
Useful Links
External resources not written by Hamilton but valuable for understanding the topic, such as industry guidelines, explanatory videos, or relevant tools.
Take an introductory look at what long-read sequencing and optical genome mapping are, and explore topics including advantages, applications, and more:
| Library preparation automation - Oxford Nanopore Technologies | Visit Website |
| Sequencing 101: long-read sequencing - PacBio | Visit Website |
| How nanopore sequencing works | Watch Video |
| Saphyr OGM Technology Overview Video | Watch Video |
Hamilton Products in Action
A collection of videos showcasing Hamilton products in use, providing practical insights into their functionality and benefits.
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Solutions for the Top 3 Challenges for Long String Genomics Workflows
Overcoming Present Bottlenecks
Challenge: Certain steps in long-string genomics workflows create bottlenecks, limiting the adaptation and scalability of these technologies. Those include the need to extract difficult-to-handle (U)HMW DNA samples due to high viscosity and sensitivity to shearing. Manual protocols require highly trained users to achieve optimal results.
For some long-read sequencing applications, size selection and fragmentation are needed, which traditionally have relatively low throughput and are time-consuming and costly steps.
Solution: With automation solutions from Hamilton for long string genomics applications, you can extract longer DNA molecules more easily than ever before by replacing challenging manual preparations with full walk-away workflows. Dedicated automation processes for on-deck size selection and shearing for long-read sequencing complement this and make these steps more cost-efficient.
Obtaining Reliable and Consistent Results
Challenge: Long-string genomics workflows involve many steps, which are prone to human error. This error can drastically affect sample quantity and quality, as well as sequencing accuracy. Adapting protocols to varying experimental needs, such as sample type or quantity, requires careful preparation and precise execution.
Solution: Replacing manual preparation with consistent automated procedures ensures that samples are always processed with identical parameters. This drives confidence in high-quality results with flexible protocols that can be adjusted to different numbers of samples.
Adapting to Increased Sample Processing Demands
Challenge: Long-string genomics applications are rapidly evolving and establishing new standards to explore the full extent of genetic variation. Therefore, the demand to process higher sample numbers is also rapidly increasing, often surpassing manual capabilities.
Solution: With our assay-ready workstations, tailored for different throughput needs, Hamilton has the right fit for every laboratory to automate their long-string genomics workflows. Implementation of biologically tested methods helps your lab to quickly achieve peak performance. This opens new possibilities to address the toughest biological questions at elevated capacities.
What is Long-Read Sequencing?
Imagine solving two jigsaw puzzles of the same image. One has significantly larger pieces than the other and is, therefore, much easier to assemble. Similarly, long-read sequencing provides longer sequence reads, offering a clearer, more comprehensive genomic picture.
With long-read sequencing, researchers gain access to significantly longer sequence data derived from single molecules, unlike traditional methods that rely on clusters of shorter DNA fragments.
The primary long-read sequencing technologies on the market today, coming from PacBio and Oxford Nanopore Technologies, each offer unique strengths and weaknesses that depend on the intended research applications. Both approaches support the analysis of genomes and their variation with unmatched resolution, enabling breakthroughs in many research areas.
What Is Optical Genome Mapping (OGM)?
Optical Genome Mapping (OGM) analyzes labeling patterns on Ultra High Molecular Weight (UHMW) DNA molecules to accurately detect all Structural Variant (SV) classes.
OGM begins with the isolation of ultra-long DNA molecules. These molecules are enzymatically labeled at a regularly occurring six-base-pair (bp) motif throughout the genome. The labeled molecules are linearized and imaged to identify variations in the labeling patterns relative to reference genomes.
Like this, large and otherwise difficult-to-identify SVs can be directly observed and do not have to be inferred, eliminating the well-known constraints of classical DNA sequencing approaches.
Long String Genomics Applications
Long-read sequencing is ideally suited for studies requiring high-resolution characterization of genes or regions that may otherwise be overlooked.
This applies to many human research areas, including:
- Rare diseases
- Repeat expansion syndromes
- Neurological and immunological disorders
- Pharmacogenomic studies
Other focus areas include microbial sequencing and plant or animal genomics, where genomes may be largely unknown or highly complex, such as:
- Infectious diseases
- Microbiology research
- Microbiome studies
- Agrigenomics
- Biodiversity studies
The analysis of UHMW DNA by OGM offers the most comprehensive way to obtain unbiased genome-wide identification of all structural variant classes over the whole size continuum. This is useful across a broad range of research applications, such as:
- Constitutional genetic disorders
- Hematological malignancies
- Solid tumors
- Cell and gene therapy quality control
Long-Read Sequencing Case Studies and Application Notes
Other Long String Genomics Resources
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
Browse app notes, user guides, specification documents, and more in our Knowledge Center.
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