Noninvasive prenatal screening using dynamic iterative depth optimization

A method for determining a chromosomal abnormality of a test chromosome or a portion thereof in a fetus by analyzing a test maternal sample of a woman carrying said fetus, wherein the test maternal sample comprises fetal cell-free DNA and maternal cell-free DNA, the method comprising:

• measuring a dosage of the test chromosome or the portion thereof in the test maternal sample;
• measuring a fetal fraction of cell-free DNA in the test maternal sample based on a count of binned sequencing reads from an interrogated region from the maternal sample;
• and
• determining an initial value of likelihood that the test chromosome or the portion thereof in the fetal cell-free DNA is abnormal based on the measured dosage, an expected dosage of the test chromosome or the portion thereof, and the measured fetal fraction.

A method for determining a chromosomal abnormality of a test chromosome or a portion thereof in a fetus by analyzing a test maternal sample of a woman carrying said fetus, wherein the test maternal sample comprises fetal cell-free DNA and maternal cell-free DNA, the method comprising:

• measuring a dosage of the test chromosome or the portion thereof in the test maternal sample;
• measuring a fetal fraction of cell-free DNA in the test maternal sample based an over- or under-representation of fetal cell-free DNA relative to maternal cell-free DNA from a plurality of bins within an interrogated region from the maternal sample;
• and
• determining an initial value of statistical significance for the test chromosome or the portion thereof based on the measured dosage and an expected dosage of the test chromosome or the portion thereof.