What does OrbiSeq™ Analyze?

Orbit Genomics’ patent-pending OrbiSeq technology platform analyzes repetitive DNA, short tandem repeats, STRs, known as microsatellites that uniquely reflect both inherited predisposition to disease and risk acquired from lifestyle, including environmental exposures. OrbiSeq is not Microsatellite Instability Testing, MSI, which compares a few microsatellites in tumors to normal tissue. OrbiSeq analyzes microsatellites throughout the entire genome and is the only platform that can. DNA sequencing algorithms are optimized for Single Nucleotide Polymorphisms, SNPs, and do not correctly assemble repetitive DNA, microsatellites.  Orbit Genomics’ OrbiSeq technology platform uses proprietary alignment and calling algorithms which increase the accuracy for genotype calling from 20% to 95%, making the discovery of these informative microsatellites in what others would see as noise possible. This technology is based on over 20 years of research which includes 7 NIH Grants totaling $15.6 Million resulting in over 45 scientific published studies co-authored by our CSO, Skip Garner. Recent improvements in NextGen sequencing combined with the addition of AI to our algorithms enable us to develop clinically actionable products. Through the analysis of thousands of human cellular DNA from blood genome sequences, comparing diseased and healthy genomes, we have identified clinically actionable microsatellite regions which are specific to different diseases and conditions. Orbit Genomics has also used this technique to compare different traits in responders and non-responders to a given therapy to develop companion diagnostics for new or established drugs.

The OrbiSeq technology platform is applicable to many diseases and conditions beyond cancer. Because microsatellites reflect overall genome stability and mutate rapidly, they are an ideal regions of interest for diseases and conditions of the aged. 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, defined as tandem repeats of 1- to 6 base pairs, are pervasive throughout the human genome in both coding and non-coding regions. An example is the DNA sequence, CAGCAGCAGCAGCAG, where CAG is repeated 5 times. There are approximately one million microsatellites in the human genome.

Microsatellites are mostly known for their role in forensics and paternity testing. About 20 microsatellites, which are known to vary among individuals, are measured for all forensics and paternity testing. There are also tests known as microsatellite instability testing which compares tumor DNA to germline DNA for a few microsatellites.  Telomeres are another example of microsatellites.  They are at the end of chromosomes and are known to play a role in longevity.

Orbit Genomics explores all of the microsatellites in the genome and our technology is very different from other tests. Standard DNA sequencing algorithms are optimized for 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, where a single DNA base (or nucleotide) changes, for example a G to an A, are often studied for their role in disease. Although they have been studied extensively, they fall far 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, which is why they are both more mutable and more responsive to cellular stressors and environmental selection pressure.  Being more susceptible to stressors and being more mutable means that they are a more sensitive readout of overall cellular and organism health, providing better disease indication.  Microsatellites mutate by changing in the number of repeats (length) and have an infinite number of possible alleles (states), whereas SNPs have but 4 possible states. Microsatellites have been referred to as nature’s tuning knobs and may be there for rapid response to cellular and environmental stress, assuring survival.

Historically, microsatellites were initially used as linkage markers and are used as forensics markers, so they are viewed as something so random that they cannot play a role in disease.  However, there are diseases where microsatellites are causative (Huntington’s, Fragile x, CAG diseases, etc.). Also, the small subset of forensics/paternity markers were chosen from among the hundreds of thousands of microsatellites precisely because they were more variable across individuals and not under any apparent selection pressure. Thus, those markers used for forensics are indeed more varied but are still inherited.