Electronic Genome Mapping
Genome Mapping
Structural variants remain widely understudied despite being a major form of variation in the human genome. Sequencing-by-synthesis (SBS) is a highly effective tool for detecting small changes in genetic sequence such as single nucleotide polymorphisms (SNPs) and small insertions and deletions (indels), but fails when larger variants are present. Genome mapping expands our understanding of structural variation offering a comprehensive view beyond SNPs and short indels.
Electronic Genome Mapping
Nabsys, the pioneer of electronic genome mapping (EGM), uses solid-state nanodetectors to survey long DNA molecules to construct high-density maps with long-range information to detect structural variants (SVs). Unlike other DNA mapping technologies that rely on the use of expensive optical imaging or fluorescent labels whose resolution is inherently limited by light diffraction, EGM identifies tags in close proximity thereby producing superior resolution. This high-density information makes it possible to identify both balanced and unbalanced SVs as small as 300 bp, in addition to larger chromosomal aberrations and genetic variation missed by NGS. EGM involves simple, intuitive workflows eliminating the need for cytogenetics technical expertise, while delivering on the promise of easy-to-use, accurate, low cost, whole-genome SV analysis.
The Underlying Technology
The novel, solid-state nanodetectors developed by Nabsys are central to EGM. The highly innovative OhmX-8 nanodetector houses 256 parallel nanochannels, each with its own electronic sensor. Nabsys has developed DNA tagging chemistry that provides a high signal-to-noise ratio designed for superior detection in EGM. The high signal and spacial resolution allows tags to be more closely spaced on the high molecular weight DNA molecules. This yields optimal tag density such that structural variations as small as 300 bp can be routinely identified and mapped genome-wide.
Current Blockade Detection
When an object occupies a significant space in a current path, it creates a detectable electronic current blockade. Coated DNA in a nanochannel reduces current flow, with larger coated and tagged DNA, causing a greater blockade. Measuring these current blockades provides information about the stretches of DNA that are tagged and untagged. Transit times for these segments are converted to physical distances using advanced signal processing algorithms. The unique spacing between tags can be aligned and mapped to reference sequences, allowing identification of structural variants in the sample compared to reference sequences. This method is particularly useful for mapping very long DNA molecules (>100 kb) with greater reliability than other techniques.
Explore the EGM Pipeline
