Extended Data Fig. 5: Gene expression and genomic abnormalities in MSL-disrupted cells.

a, Karyotyping of MSL^LOF (MSL3-KO) TDF cells. The lines represent the consensus value for genomic segments that are either gained (positive values) or lost (negative values) relative to the rest of the genome (see Methods). The black dots are experimental values for 1 Mb intervals. X and Y chromosomes, which affects the performance of QDNASeq⁶⁶, are excluded from the analysis. b, Correlation between large-scale changes in mRNA levels and DNA copy number alterations in MSL^LOF (MSL3-KO) cells. For each positional gene set identified as upregulated or downregulated in MSL^LOF cells by GSEA analysis, the relative copy number changes detected by CNVkit are shown. Chromosome 1 is shown to illustrate that even though CNVKit did not call copy number changes, likely because only a subset of cells in the population were affected by consistent gains or losses, the p arm showed a relative reduction compared to control cells (cntr-KO), correlating with apparent downregulation of the corresponding genes. The slight difference compared to the Chr.1 pattern observed in the comparison with WT cells is likely due to subsampling of the population upon sgRNA transfection in the cntr-KO sample. Note that the genetic drivers in TDF cells are located in chromosomal regions showing highly significant changes, which indicates high prevalence in the population of MSL^LOF cells: HRAS on chr11p15 - gained, p53 on chr17p13 – lost, and hTERT on chr5 p15 – gained. This pattern suggests selection of less deleterious karyotypes in the population, compared to random gains or losses of other regions.