Fig. 3: Fetal fraction amplification (FFA) improves detection of fetal chromosome abnormalities by amplifying the signal of aneuploid regions while maintaining background noise.
(a) Schematic of the change in median depth per autosome as a result of FFA. The extent of the deviation from background is itself a measure of FF and is indicated as FFpositive. (b) The increase in FFpositive without FFA (gray circles) and with FFA (purple triangles) is shown for aneuploid samples with the indicated chromosome anomalies. (c, d) z-scores without FFA (gray) and with FFA (purple) for the same samples as in (b) are stratified by their screening results and summarized either as population distributions (c) or as individual samples (d). For visual clarity in (c), the distribution of screen-negative samples (NEG.; dashed line) has been scaled to be of comparable height as the screen-positive distributions to the right (solid lines). The vertical solid line indicates the z-score cutoff between screen-negative (left) and screen-positive (right) results. For SCAs, only female fetus pregnancies are shown (i.e., MX and TX) because a z-score is used to identify chrX aneuploidies, whereas a two-dimensional analysis that does not use z-scores (not shown) is required for identification of XXY and XYY (FFpositive increased in all XXY and XYY pregnancies tested with FFA). NIPS noninvasive prenatal screening, RAA rare autosomal aneuploidies, SCA sex chromosome aneuploidies.
