Harmony Test Technology

Harmony test targeted technology - DANSR assay and FORTE algorithm

The DANSR assay technology specifically targets just the chromosomes of interest for deep, directed analysis.1 This reduces complexity of unutilized sequencing data compared to massively parallel shotgun sequencing (MPSS) techniques.1, 2

In practice, DANSR assay technology significantly improves assay efficiency and reduces overall test cost.2  Together the DANSR assay and FORTE algorithm are optimized to provide a streamlined workflow.

DANSR assay approach and benefits

  • Specific chromosomes of interest are targeted by hundreds of DANSR assays
  • Eliminates lengthy and time-consuming whole genome data generation2
  • Enables streamlined workflow

Single Nucleotide Polymorphism (SNP) analysis for fetal fraction

Reliable NIPT results require an accurate fetal fraction assessment.3

The Harmony test uses SNPs to analyze and report fetal fraction for every sample. SNPs are the most common type of genetic variation between individuals, with a normal occurrence of one in every 300 nucleotides.4,5 Detection of these variations allows for accurate determination of fetal fraction.6

  • Hundreds of SNPs are analyzed
  • Fetal fraction is determined for every sample
  • Ensures sufficient fetal fraction for accurate NIPT

 

Failure to accurately measure fetal fraction can lead to erroneous results based on maternal DNA3

  • Researchers submitted the blood of two non-pregnant women for NIPT at five different laboratories and found:
    • Three out of five laboratories reported a negative screen consistent with a female fetus
    • One laboratory reported, and quantified, a fetal fraction too low to perform NIPT
    • The Harmony Test accurately reported insufficient fetal fraction with no misleading results*

      *Blinded samples. NIPT manufacturer results identified by results reporting convention.

 

NIPT Results for Two Non-pregnant Women3
 

PATIENT 1

 

PATIENT 2
 

LABORATORY TEST

RESULTS

DETAILS

RESULTS

Details

Harmony Prenatal Test

No

Insufficient fetal cfDNA

No

Insufficient fetal cfDNA

Panorama

No

Unable to report due to low fetal fraction (0.6%)

No

Unable to report due to low fetal fraction (0.6%)

MaterniT21

Yes

4.3% fetal fraction, negative screen consistent with female fetus

Yes

3.9% fetal fraction, negative screen consistent with female fetus

Illumina-based NIPT

Yes

XX fetus, no aneuploidy detected

Yes

XX fetus, no aneuploidy detected

Illumina-based NIPT

Yes

XX fetus, no aneuploidy detected

Yes

XX fetus, no aneuploidy detected

Custom microarray precision

DANSR assay is a proprietary analysis highly targeted for the specific chromosomes of interest. As such, it is extremely well-suited to take advantage of the benefits of microarray technology.

Incorporation of microarray technology results in decreased variance in chromosome cfDNA counts, increased fetal fraction precision, lower cost and dramatically reduced time-to-result.2

Advantages of the Harmony test on microarray

  • Improves assay precision two-fold compared to next-generation sequencing2
  • Increases SNP assays for fetal fraction approximately 3-fold compared to next-generation sequencing, making the fetal fraction measurement more accurate2

FORTE algorithm

The FORTE algorithm is the proprietary analysis for the Harmony test, which is included in the AcfS Software. It incorporates individual patient factors including fetal fraction, maternal age, and gestational age to clearly distinguish between high and low probability results.7 Compared with commonly utilized Z-Statistic scoring, FORTE provides greater discrimination between true positive and true negative results.7

FORTE approach and benefits

  • Targeted analysis plus patient factors generate an individually weighted probability assessment7
  • Clearer separation between low and high probability results provides greater confidence even at low fetal fraction 

References

 
  1. Sparks et al. Prenat Diagn. 2012 Jan;32(1):3-9.
  2. Juneau et al. Fetal Diagn Ther. 2014. 36(4)282-6.
  3. Takoudes and Hamar. Ultrasound Obstet Gynecol 2015; 14:112-116. 
  4. https://ghr.nlm.nih.gov/chromosome
  5. https://ghr.nlm.nih.gov/primer/genomicresearch/sn Accessed April 24, 2017
  6. Schmidt et.al  Ultrasound Obstet Gynecol. 2018 Feb  doi.org/10.1002/uog.19036
  7. Sparks et al. Am J Obstet Gynecol. 2012;206(4):319e1-9