A novel method that enhances short-read genome sequencing with long-distance information for exceptional genome mapping and insights
Illumina sequencing-by-synthesis (SBS) has significantly advanced genome mapping methods over the past 20 years, helping researchers achieve highly accurate coverage over the vast majority of the human genome.1 However, for a small percentage of the genome, mapping short reads to a reference genome remains challenging. These challenges primarily occur in repetitive or low-complexity regions, regions that have high homology with other parts of the genome, or large structural variations.
Mapped read technology leverages on-flow cell library preparation and novel informatics that incorporate proximity information from clusters in neighboring nanowells to generate long-range genomic insights. The unique workflow maintains the link between the original long DNA template and the resulting short sequencing reads, enabling improved mapping in low-complexity regions, ultra-long phasing of genetic variants, and enhanced detection of structural variants.
See how mapped read technology can simplify your NGS workflow and view examples of how the technology can help improve genomic insights in challenging genomic regions and analysis scenarios.
Mapped read technology uses a unique workflow that provides comprehensive genome analysis.
On-flow cell library prep creates a highly streamlined workflow for genome sequencing
SBS chemistry provides proven accuracy and scalability
Cluster proximity analysis unlocks exceptional long-distance information
Enhanced mapping resolves challenging variants and genomic regions
Novel method improves detection of large structural rearrangements
In mapped read technology, DNA templates are extracted from samples using standard or high molecular weight methods and introduced directly to the flow cell surface, where they are captured, transformed into clusters through a process called tagmentation and sequenced. By introducing long DNA templates directly to the flow cell, proximal nanowells produce a constellation-like pattern that allows clusters to be mapped back to the original template using novel algorithms in DRAGEN secondary analysis. This significantly improves mapping reads to a reference genome and allows researchers to unlock long-range genomic insights with the accuracy and scalability of short-read SBS sequencing.
Figure 1a: Aerial view of constellation pattern
Figure 1b: Side view of constellation pattern
Figure 1: DNA attaches to the flow cell in a constellation pattern. The top view illustrates a small percentage of the tile showing DNA strands across the flow cell. The side view illustrates the template DNA undergoing tagmentation on the flow cell.
Dr Stephen F. Kingsmore, President and Chief Executive Officer of Rady Children's Institute for Genomic Medicine, shares his perspective on mapped read technology and its potential impact on rapid whole-genome sequencing for rare genetic disease.
Hear Dr Steven Barnard from Illumina describe the latest Illumina innovations enabling revolutionary multiomic applications. Dr Niall Lennon from the Broad Institute of MIT gives his impressions on the workflow, early data, and exciting potential of mapped read technology.
Illumina mapped read technology is currently being developed for the NovaSeq X Series and compatibility has been demonstrated with benchtop sequencing systems. Analysis will use a novel DRAGEN secondary analysis pipeline and be compatible with the Illumina whole-genome tertiary analysis solution.
No, the experimental workflow does not require modifications to the sequencing system. The method only requires a novel sequencing recipe, making it readily accessible to researchers.
Long-read sequencing enables sequencing of intact long DNA molecules. The mapped read technology workflow introduces long template DNA directly to a patterned flow cell; proximal nanowells have a high probability of containing DNA from the same template. Reads can be informatically mapped with high confidence for applications that include detection of large structural variations, mapping low-complexity regions, and ultra-long phasing of variants.
Read mapping describes the process of determining the genomic location from which a sequence read originates. Alignment involves identifying similarities between two or more sequences. For example, a single read can align to more than one place in the genome but will only accurately map to one. Mapped read technology supports both mapping reads to a reference genome and alignment analysis.
The 5-base bioinformatics solution does not require advanced expertise. It offers highly accurate variant and methylation detection. This is a simple, powerful, and easy-to-use multiomic analysis solution. Insights from Illumina Connected Multiomics are powered by DRAGEN analysis.
Performing analysis with mapped read technology
Louise Fraser, PhD, Associate Director in Assay Research and Development at Illumina, describes how mapped read technology, formerly constellation mapped reads, works and the types of analysis that can be performed.
Mapped read technology overview and data highlights
See how on-flow cell library prep and proximity information from neighboring nanowells enable long-range genomic insights.
Poster
Structural variant detection with proximity mapping
Gain deep insights into complex regions of the genome such as highly repetitive regions, large inversions, and translocations.
Get an unbiased view of the entire human genome and evaluate the genetic variants that encode human traits and disease.
Genomics is driving a fundamental shift in understanding the genetic variants underlying rare diseases.
Gain deep insights into complex regions of the genome such as highly repetitive regions, large inversions, and translocations.
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