Abstract
Rapid advances in single-cell genomics sequencing (SCGS) have allowed researchers to characterize tumor heterozygosity with unprecedented resolution and reveal the phylogenetic relationships between tumor cells or clones. However, high sequencing error rates of current SCGS data, i.e., false positives, false negatives, and missing bases, severely limit its application. Here, we present a deep learning framework, RDAClone, to recover genotype matrices from noisy data with an extended robust deep autoencoder, cluster cells into subclones by the Louvain-Jaccard method, and further infer evolutionary relationships between subclones by the minimum spanning tree. Studies on both simulated and real datasets demonstrate its robustness and superiority in data denoising, cell clustering, and evolutionary tree reconstruction, particularly for large datasets.