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. 2021 Sep 6;10:e66198. doi: 10.7554/eLife.66198

Figure 1. Telomere content and related genomic features across human cell lines.

Cell lines were grouped by cancer type and ordered by telomere content within each type, and are displayed such that each column represents a cell line. Telomere content measurements reflect combined z-scored estimates derived from CCLE WGS and GDSC WES with means for samples with telomere content estimates from both sources. Bars within each cancer type represent medians. Relative copy number values are shown as log2(relative to ploidy + 1)–1. Cell lines shown are filtered such in addition to annotations for telomere content, values for TERT and TERC RNA-seq expression, TERT and TERC copy number, and ATRX and DAXX mutation status are all available (with an exception made for non-cancerous cell lines, which lack such profiling in DepMap). Cell lines were also filtered such that each cancer type is represented by at least 10 cell lines (n = 738 cell lines total). RNA expression estimates are in terms of log2(TPM+1). CNS: central nervous system; PNS, peripheral nervous system; UADT, upper aerodigestive tract.

Figure 1.

Figure 1—figure supplement 1. Overlap between cell lines represented in annotations.

Figure 1—figure supplement 1.

Heatmap of cell lines (columns) and annotations (rows). Colored cells indicate cell lines profiled for specific annotations, and gray cells indicate cell lines missing annotations.
Figure 1—figure supplement 2. Telomere content agreement between sequencing sets.

Figure 1—figure supplement 2.

(a) Pairwise correlations between cell lines in overlaps of the indicated sequencing sets. Telomere content estimates are displayed as z-scored values of log2-transformed raw content estimates. p Values determined by two-sided Pearson’s correlation test. (b) Distribution of counts for reads with six or more telomeric repeats across samples in the three sequencing datasets used.
Figure 1—figure supplement 3. Telomere content, age, and tissue subtype.

Figure 1—figure supplement 3.

(a) Correlation between donor age and z-scored and log2 transformed telomere content estimates from CCLE WGS (left) and GDSC WES (right) telomere content estimates as labeled. (b) Correlation between doubling time and z-scored and log2 transformed telomere content estimates from CCLE WGS (left) and GDSC WES (right) telomere content estimates as labeled. (c and d) Distribution of z-scored log2-transformed telomere content estimates across origin tissue subtypes of the CCLE WGS and GDSC WES datasets, respectively. Tissue subtypes with less than five samples are omitted. Bars denote bootstrapped 95% confidence intervals, with central lines denoting means. CNS, central nervous system; PNS, peripheral nervous system; UADT, upper aerodigestive tract.
Figure 1—figure supplement 4. Transcriptomic associations between TERT, TERC, and telomere content.

Figure 1—figure supplement 4.

(a and b) Pearson correlations between log2(TPM + 1) levels of TERT mRNA and telomere content within tissue subtypes in the CCLE WGS and GDSC WES datasets, respectively. CNS, central nervous system; PNS, peripheral nervous system; UADT, upper aerodigestive tract. (c) Associations between total TERT (ENSG00000164362.14) mRNA, full-length TERT (ENST00000310581.5) mRNA, minus-beta TERT (ENST00000296820.5) mRNA, TERC (ENSG00000270141.2) RNA, and z-scored log2-transformed telomere content estimates in the CCLE WGS and GDSC WES datasets. mRNA expression measured as log2-transformed TPMs with a pseudocount of +1. (d) Associations between exon inclusion levels of TERT exons 7 (GRCh37: chr5:1272395–1272300) and 8 (GRCh37: chr5:1271319–1271234) and telomere contents as described previously. (e) Distribution of correlations between TERC RNA levels and other RNAs (n = 1,019 cell lines), with scaRNAs and histone pre-mRNAs highlighted.
Figure 1—figure supplement 5. Associations between telomere content and cell line characteristics.

Figure 1—figure supplement 5.

(a) Distributions of z-scored log2-transformed telomere content estimates from merged CCLE WGS and GDSC WES estimates, stratified by mutations in TP53, ATRX, DAXX, IDH1, and VHL. Boxes, interquartile range (IQR); center lines, median; whiskers, maximum and minimum or 1.5 × IQR; notches, 95% confidence interval of bootstrapped median using 1000 samples and a Gaussian-based asymptotic approximation. *p < 0.05, two-sided Mann-Whitney U test against WT/silent category; n.s, not significant. (b) Volcano plots of normalized correlation coefficients and false discovery rates (q values) of associations between merged telomere content estimates and several profiling datasets. Correlation coefficients were computed by regressing telomere content versus each indicated feature with cancer type as a covariate. Sample sizes listed in Supplementary file 2. p Values determined using two-sided Pearson’s correlation test.