Technology

New innovations reduce the barriers to genetic testing

OS-Seq targeted NGS technology has made genetic testing so quick and cost-efficient that you can realistically choose it as a diagnostic tool in the initial stages of patient care.

Oligonucleotide-Selective Sequencing, or OS-Seq™ is the new method in genetic testing that will lead us toward earlier confirmed diagnoses. OS-Seq is a unique, patented targeted sequencing innovation developed at Stanford University. It is an effective DNA sequencing approach utilizing next-generation sequencing (NGS) technology that enables rapid, high-quality analysis of genes relevant to specific diseases. This method also costs much less and has a faster turnaround time than traditional genetic testing. With OS-Seq’s high-throughput sequencing approach, tens of thousands of variants can be analyzed in a single testing run, with results presented for all known mutations.

What takes months of processing using traditional methods can be back with the clinician in just 21 days using OS-Seq. This revolutionary process has made genetic testing so quick and cost-efficient that you can realistically choose it as a diagnostic tool in the initial stages of patient care.

Technology

Blueprint Genetics is applying a powerful molecular biology approach called next-generation sequencing to analyze patients’ DNA. Changes in DNA sequence can cause errors in proteins and result in severe medical conditions. Hereditary diseases are caused by mutations originating in germ cells and presenting in all cells of an individual. Determining the underlying DNA changes creates opportunities to diagnose hereditary diseases, estimate the prognosis and select adequate preventive treatments.

Next-generation sequencing is enabling comprehensive analysis of hundreds of clinically relevant target genes in a time frame that facilitates clinical actions. DNA sequencing detects different types of mutations exchanging single nucleotides (point mutations) or adding or removing nucleotides (insertions and deletions).

Blueprint Genetics is applying a targeted sequencing approach called Oligonucleotide-Selective Sequencing OS-Seq™ (Myllykangas et al. 2011), developed at Stanford University, to analyze disease-specific gene panels. With targeted sequencing, it is possible to identify all mutations that have been previously linked to specific genetic disorders as well as novel variants in the disease-associated genes.

(References: Myllykangas, Buenrostro, Natsoulis, Bell and Ji. Efficient targeted resequencing of human germline and cancer genomes by oligonucleotide-selective sequencing. Nature Biotechnology 2011;11:1024-7. Link.)

High-quality sequencing

  • In average, 99.8 % of base pairs in target region covered at least 15x depth
  • Highly uniform sequencing depth across all target genes
  • >99.9% sensitivity and specificity for SNPs 
  • 100.0% sensitivity for <5bp indels
  • 80% reduction in manual sample preparation steps compared to other methods

Effective Bioinformatics Pipeline

Dedicated Computing Infrastructure Analysis of data from NGS applications is a complex process, imposing challenging requirements both in terms of computing resources and software. The proprietary automated bioinformatics pipeline developed and employed at Blueprint Genetics, enables fast, reliable and highly accurate results.

Minimized False Positive Rate

In addition to incorporating state-of-the-art algorithms for quality control, alignment and variant calling, the pipeline also employs filtering steps to remove common variants based on allele frequencies in population cohorts. Moreover, the functional consequence of amino acid changes are predicted with multiple in silico tools increasing the accuracy in the identification of potentially pathogenic variants.

Results Validation

To further aid the process of variant interpretation, results are matched against a comprehensive set of databases of disease-related mutations, collected and curated in-house, and accessed from the public domain or licensed from commercial sources. In summary, the bioinformatics pipeline at Blueprint Genetics is designed to provide our geneticists with comprehensive and accurate information in the minimum amount of time.