What does OrbiSeq™ Analyze?

Orbit Genomics’ patent pending OrbiSeq technology platform analyzes repetitive DNA sequences known as short tandem repeats (STRs) or microsatellites. These sequences uniquely reflect both inherited predisposition to disease and risk acquired from lifestyle, including environmental exposures. OrbiSeq is not Microsatellite Instability (MSI) Testing, which compares a few microsatellites in tumors to normal tissue. Instead, OrbiSeq analyzes microsatellites throughout the entire genome and is the only platform that can. Standard DNA sequencing algorithms are optimized for Single Nucleotide Polymorphisms (SNPs) and do not correctly assemble repetitive DNA such as microsatellites. Orbit Genomics’ OrbiSeq technology platform uses proprietary alignment and allele calling algorithms that increase the accuracy for genotype calling from 20% to 95%. OrbiSeq enables the discovery of informative microsatellites in data that would be seen as noise by other technologies. The platform is based on over 20 years of research, supported by 7 NIH Grants totaling $15.6 Million, resulting in over 46 scientific published studies co-authored by our CSO – Dr. Harold “Skip” Garner. Recent improvements in NextGen sequencing combined with the addition of AI to our algorithms enable us to develop clinically actionable products. By analyzing thousands of human DNA sequences from blood samples and comparing diseased and healthy genomes, we have identified clinically actionable microsatellite regions which are specific to various diseases and conditions. Additionally, Orbit Genomics has also used this technique to develop companion diagnostics for drugs by comparing different traits in responders and non-responders to a given therapy.

The OrbiSeq technology platform is applicable to many diseases and conditions beyond cancer. It can be applied to any complex disease, including heart disease and neurological diseases. Microsatellites mutate rapidly and reflect overall genome stability, making them ideal regions of interest for age related diseases and conditions. We’ve demonstrated the ability to detect disease early and predict drug efficacy in individuals (CDx). OrbiSeq can also identify therapeutic targets for diseases.

What are microsatellites?

Microsatellites, or repetitive DNA, are defined as tandem repeats of 1 to 6 base pairs. They are pervasive throughout the human genome in both coding and non-coding regions. For example, the DNA sequence “CAGCAGCAGCAGCAG” contains a “CAG” motif that is repeated 5 times. There are approximately one million microsatellites in the human genome.

Microsatellites are most well-known for their role in forensic and paternity testing. About 20 microsatellites that are known to vary among individuals are measured for all forensic and paternity testing. Other tests, known as microsatellite instability testing (MSI), compare a few microsatellites in tumors to normal tissue. Telomeres are another example of genomic regions containing microsatellites.  They are located at the end of chromosomes and are known to play a role in longevity.

Orbit Genomics explores all of the microsatellites in the genome, providing a very different approach from other tests. Standard DNA sequencing algorithms are optimized for single base genetic mutation (SNP) analysis and don’t accurately analyze microsatellites. OrbiSeq’s proprietary algorithms incorporate AI and accurately analyze all one million microsatellites in the genome.

How are they different from other DNA sequence variations in the human genome?

Most genetic and genomic studies have focused on SNPs. These variants are characterized by a single DNA base (or nucleotide) change (for example a G to an A), and are often studied for their role in disease. Despite extensive study, they fall short of explaining the known or suspected genetic components of disease – especially complex diseases such as cancer, heart, or neurological diseases. Over 50 hereditary cancer syndromes have been identified: yet inherited mutations only account for 5-10% of all cancers. Complex diseases are caused by a combination of genetic mutations and environmental factors.

Microsatellites are under fundamentally different biological processes for replication and error correction than SNPs, making them more mutable and responsive to cellular stressors as well as environmental selection pressure. This characteristic means that they are a more sensitive readout of overall cellular and organism health, providing better disease indication. Microsatellites have been referred to as nature’s genetic tuning knobs and may be there for rapid response to cellular and environmental stress, assuring survival. When a microsatellite mutates it changes in the number of repeats (length), offering an infinite number of possible states (alleles). Comparatively, SNPs have only four possible states.

Historically, the unique characteristics of microsatellites led them to be used as linkage markers and as forensic markers. This led to a reputation of being too “random” to play a role in disease.  However, there are diseases where microsatellites are causative such as Huntington’s, Fragile X Syndrome, and CAG diseases. The small subset of forensic/paternity markers were chosen from among hundreds of thousands of microsatellites precisely because they were more variable across individuals and not under any apparent selection pressure.