Shallow whole genome sequencing is well suited for the detection of chromosomal aberrations in human blastocysts  Lieselot Deleye, M.Sc., Annelies Dheedene, M.Sc., Dieter De Coninck, Ph.D., Tom Sante, M.Sc., Christodoulos Christodoulou, M.Sc., Björn Heindryckx, Ph.D., Etienne Van den Abbeel, Ph.D., Petra De Sutter, Ph.D., Dieter Deforce, Ph.D., Björn Menten, Ph.D., Filip Van Nieuwerburgh, Ph.D.  Fertility and Sterility  Volume 104, Issue 5, Pages 1276-1285.e1 (November 2015) DOI: 10.1016/j.fertnstert.2015.07.1144 Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Schematic overview of the experimental design of this study. After whole genome amplification of trophectoderm biopsies, routine microarray analysis was performed. Remaining amplified DNA was used to sequence samples on a Nextseq 500 and Ion Proton sequencer in parallel. Fertility and Sterility 2015 104, 1276-1285.e1DOI: (10.1016/j.fertnstert.2015.07.1144) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 2 Comparing arrayCGH and MPS profiles for chromosomal aberrations. Genomic profiles from Patient 2 embryo 8 generated with (A) NextSeq500 sequencing, (B) Ion Proton sequencing, and (C) arrayCGH. The blue color indicates a duplication or trisomy, whereas the red color indicates a deletion or monosomy. All sequencing results were analyzed with a female reference and a male reference was used in the arrayCGH experiments. The arrayCGH profiles were analyzed with a 1-Mb distance between the probes, which leads to a smoother line compared to the 500-kb windows from sequencing results. Fertility and Sterility 2015 104, 1276-1285.e1DOI: (10.1016/j.fertnstert.2015.07.1144) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Figure 3 The resolution and signal-to-noise is more appropriate for MPS analysis. (A) Sequencing (top) and arrayCGH (bottom) profile of chromosome 6 from Patient 10 embryo 1. The 6q23.2q24.3 duplication due to the paternal insertional translocation (46,XY,ins(14;6)(q23.2;q23.2q24.3)) is more clearly detected on the MPS profile than on the array profile. (B) Sequencing (top) and arrayCGH (bottom) profile of chromosome 9 from Patient 2 embryo 7. The 4.5-Mb duplication on chromosome 9 is unequivocally apparent in the MPS data, whereas it is less obvious in the array profile. The abnormalities are highlighted with a red arrows. Fertility and Sterility 2015 104, 1276-1285.e1DOI: (10.1016/j.fertnstert.2015.07.1144) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions

Supplemental Figure 1 Only one tenth of the reads is needed for detecting the chromosomal aberrations of ≥4.5 Mb. To determine the minimum number of reads necessary to detect copy number aberrations successfully, raw reads were randomly down-sampled to levels 2–10 times lower than the original number of raw reads. (6) Original genomic MPS profile of Patient 2 embryo 7. (1) Genomic MPS profile of Patient 2 embryo 7 with the 10× less reads. All aberrations from the original sample could still be detected after down-sampling. Fertility and Sterility 2015 104, 1276-1285.e1DOI: (10.1016/j.fertnstert.2015.07.1144) Copyright © 2015 American Society for Reproductive Medicine Terms and Conditions