An Interactive Resource to Probe Genetic Diversity and Estimated Ancestry in Cancer Cell Lines

Abstract

Recent work points to a lack of diversity in genomics studies from genome-wide association studies to somatic (tumor) genome analyses. Yet, population-specific genetic variation has been shown to contribute to health disparities in cancer risk and outcomes. Immortalized cancer cell lines are widely used in cancer research, from mechanistic studies to drug screening. Larger collections of cancer cell lines better represent the genomic heterogeneity found in primary tumors. Yet, the genetic ancestral origin of cancer cell lines is rarely acknowledged and often unknown. Using genome-wide genotyping data from 1,393 cancer cell lines from the Catalogue of Somatic Mutations in Cancer (COSMIC) and Cancer Cell Line Encyclopedia (CCLE), we estimated the genetic ancestral origin for each cell line. Our data indicate that cancer cell line collections are not representative of the diverse ancestry and admixture characterizing human populations. We discuss the implications of genetic ancestry and diversity of cellular models for cancer research and present an interactive tool, Estimated Cell Line Ancestry (ECLA), where ancestry can be visualized with reference populations of the 1000 Genomes Project. Cancer researchers can use this resource to identify cell line models for their studies by taking ancestral origins into consideration.

Figure 1.

Estimated genetic ancestry of cell lines within key cell line panels with the 1000 Genomes Project (1kG) reference populations. (A) t-SNE plot of SNP data for cell line panels and 1kG reference populations where each reference population is labeled with the 1kG label (see Table S8 for abbreviation definitions) and the cell lines are labeled as small purple circles primarily clustered in the JPT (Japan), GBR (Great Britain) and CEU (Utah residents with Northern and Western European Ancestry) clusters indicating the majority of cell lines are limited to a few major genetic ancestral groups. (B) Principal Component Analysis (PCA) plot of the cell line panels with the 1kG reference populations. (C) Panel of t-SNE plots showing specific estimated admixture component of ancestral populations estimated through an Admixture analysis with 1kG references and cell lines (7 populations, Q1-Q7 – see Table S5 for Admixture proportions). Shown are samples with majority admixture (Q1–7 color) for the specific population. Waterfall plots show the relative component fraction in each cell line and 1kG sample.

Figure 2.

Stacked barplots of the proportion of cell lines within population by disease type. For each annotated disease type, the cell lines are summarized by cell line panel. Each bar represents the proportion of cells within the group with the majority admixture belonging to one of 6 groups (AA: African American, AFR: African, EAS: East Asian, EUR: European, H/L: Hispanic/Latino, SAS: South Asian). The results clearly indicate the overwhelming proportion of European-ancestry cell lines within the panels.