The IONA® Test: Development of an Automated Cell-Free DNA-Based Screening Test for Fetal Trisomies 13, 18, and 21 That Employs the Ion Proton Semiconductor Sequencing Platform.
OBJECTIVE
To develop a screening test for fetal trisomy 13, 18, and 21 using cell-free DNA from maternal blood with an automated workflow using the Ion Proton sequencing platform.


METHODS
An automated next-generation sequencing workflow was developed using the Ion Proton sequencing platform and software developed for straightforward bioinformatic analysis. An algorithm was developed using 239 samples to determine the likelihood of trisomy, using DNA fragment counts and a fetal fraction validity check; the results were compared with those from invasive diagnostic procedures. A further 111 samples were used to assess the tests' sensitivity (detection rate) and specificity (1 minus false-positive rate).


RESULTS
The 110 of a possible 111 valid samples used to verify the IONA® test gave 100% sensitivity and specificity, compared with invasive diagnostic procedures; one failed the fetal fraction validity check giving a sample failure rate of 0.29% across all 350 analysed samples.


CONCLUSIONS
The data indicate that the IONA test provides a robust, accurate automated workflow suitable for use on maternal blood samples to screen for trisomies 13, 18, and 21. The test has the potential to reduce the number of unnecessary invasive procedures performed and facilitate testing by screening laboratories.
Premaitha Health plc, Manchester, UK.
Francesco
F
Crea
Matthew
M
Forman
Rachel
R
Hulme
Robert W
RW
Old
Dan
D
Ryan
Rosalyn
R
Mazey
Michael D
MD
Risley
D000073888:Cell-Free Nucleic Acids / Q000737:chemistry; D004314:Down Syndrome / Q000235:genetics; D005260:Female; D006801:Humans; D062145:Maternal Serum Screening Tests / Q000379:methods*; D011247:Pregnancy; D011261:Pregnancy Trimester, First; D014314:Trisomy / Q000235:genetics*; D000073839:Trisomy 13 Syndrome / Q000235:genetics; D000073842:Trisomy 18 Syndrome / Q000235:genetics
D000073888:Cell-Free Nucleic Acids
Cell-free DNA; First-trimester screening; Next-generation sequencing; Noninvasive prenatal screening; Trisomy