title: Comparative evaluation of the Minimally-Invasive Karyotyping (MINK) algorithm for non-invasive prenatal testing.
abstract: Minimally Invasive Karyotyping (MINK) was communicated in 2009 as a novel method for the non-invasive detection of fetal copy number anomalies in maternal plasma DNA. The original manuscript illustrated the potential of MINK using a model system in which fragmented genomic DNA obtained from a trisomy 21 male individual was mixed with that of his karyotypically normal mother at dilutions representing fetal fractions found in maternal plasma. Although it has been previously shown that MINK is able to non-invasively detect fetal microdeletions, its utility for aneuploidy detection in maternal plasma has not previously been demonstrated. The current study illustrates the ability of MINK to detect common aneuploidy in early gestation, compares its performance to other published third party methods (and related software packages) for prenatal aneuploidy detection and evaluates the performance of these methods across a range of sequencing read inputs. Plasma samples were obtained from 416 pregnant women between gestational weeks 8.1 and 34.4. Shotgun DNA sequencing was performed and data analyzed using MINK RAPIDR and WISECONDOR. MINK performed with greater accuracy than RAPIDR and WISECONDOR, correctly identifying 60 out of 61 true trisomy cases, and reporting only one false positive in 355 normal pregnancies. Significantly, MINK achieved accurate detection of trisomy 21 using just 2 million aligned input reads, whereas WISECONDOR required 6 million reads and RAPIDR did not achieve complete accuracy at any read input tested. In conclusion, we demonstrate that MINK provides an analysis pipeline for the detection of fetal aneuploidy in samples of maternal plasma DNA.
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania, United States of America.|Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, United States of America.
authors.forename: Tianjiao
authors.initials: T
authors.lastname: Chu
authors.affiliation: Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, United States of America.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Shaw
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania, United States of America.|Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, United States of America.
authors.forename: Suveyda
authors.initials: S
authors.lastname: Yeniterzi
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Mary
authors.initials: M
authors.lastname: Dunkel
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: Aleksander
authors.initials: A
authors.lastname: Rajkovic
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania, United States of America.
authors.forename: W Allen
authors.initials: WA
authors.lastname: Hogge
authors.affiliation: Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, United States of America.
authors.forename: Kimberly D
authors.initials: KD
authors.lastname: Bunce
authors.affiliation: Department of Obstetrics, Gynecology and Reproductive Sciences, University of Pittsburgh, Pennsylvania, United States of America.|Center for Fetal Medicine, Magee-Womens Research Institute, Pittsburgh, PA, United States of America.
authors.forename: David G
authors.initials: DG
authors.lastname: Peters
mesh_terms: D000465:Algorithms; D005260:Female; D006801:Humans; D007621:Karyotyping; D011247:Pregnancy; D011296:Prenatal Diagnosis