Extended Data Fig. 7: (TA)n repeats undergo large-scale expansions in MSI cells.
From: Repeat expansions confer WRN dependence in microsatellite-unstable cancers
a, Cumulative fraction of expanded (TA)n repeats in KM12 and HCT116, based on ExpansionHunter analysis of PCR-free whole genome sequencing data. (TA)n repeats were split into broken (red) and non-broken (black) based on presence or absence of END-seq peaks after WRN depletion in KM12 cells. b, Graphical representation of a (TA)n repeat expansion in HCT116. This site has 33 (TA)n repeat units in the reference genome; ExpansionHunter identified an expansion to 86–87 repeat units based on PCR-free whole-genome sequencing of HCT116. c, Empirical cumulative distribution function based on the length by which each read overlaps the (TA)n repeat shown in b as identified by exSTRa. d, Southern blots for two different genomic regions containing non-broken (TA)n repeats corresponding to the same sites in Fig. 4a and Extended Data Fig. 6b. Red markers and dotted lines represent expected fragment sizes. For gel source data, see Supplementary Fig. 1. e, Southern blots for broken (TA)n repeat B2 (top) and non-broken (TA)n repeat NB3 (bottom) in MSS (blue) and MSI (red) cell lines, confirming expansion of broken (TA)n repeats in MSI cell lines. Red markers and dotted lines represent expected fragment sizes based on the reference genome. For gel source data, see Supplementary Fig. 1. f, Box plots displaying coverage at different classes of repeats in long-read sequencing libraries made from MSI (red) and MSS (blue) cells (n = 1). g, Motif analysis for sequence enrichment at broken (TA)n in the KM12 cell line from long-read sequencing data.
