Tumor clones differ by more than mutations: regulatory networks separate dominant clones across 253 patients and 12 cancers
Whether tumor clones can be told apart by their gene regulatory networks had remained largely unmapped, since clones are usually defined by copy-number profiles and rarely characterized by regulatory activity. Clone-specific networks were inferred from single-cell RNA-seq and compared with a Wasserstein-distance measure of regulatory divergence. Across 253 patients and 12 cancer types, clone-clone networks resembled each other more than clone-normal pairs, and the largest clone diverged from normal cells significantly more than smaller clones.