Runpeng Luo will present his General Exam "Inferring Allele-Specific Copy Number Aberrations across Different Sequencing Technologies" on Tuesday, May 5, 2026 at 3:15 PM in CS 302. Committee Members: Ben Raphael (advisor), Yuri Pritykin, Sneha Goenka Abstract: Copy-number aberrations (CNAs) are somatic mutations that alter the number of copies of a genomic segment on one or both parental chromosomes. Inferring CNAs from DNA or RNA sequencing of individual cells is important for quantifying tumor heterogeneity, reconstructing tumor evolution, and identifying the spatial organization of clones, or groups of cells with the same set of CNAs. Traditionally, CNAs were inferred from DNA sequencing of bulk tumor samples containing DNA from thousands to millions of cells, which limits the ability to identify CNAs that are present in only a subpopulation of cells in a tumor. More recently, researchers have inferred CNAs from single-cell RNA sequencing and single-cell ATAC sequencing data from tumor samples. However, neither of these technologies directly measure DNA copy number: single-cell RNA sequencing measures gene expression, and single-cell ATAC sequencing profiles open-chromatin accessibility. Thus, the inference of CNAs from these technologies is complicated by transcriptional or epigenetic variation as well as the sparse and noisy measurement in individual cells. To address these challenges, we studied the setting in which both single-cell sequencing data and bulk DNA sequencing data are available from the same patient. We formulated the single-cell clone inference problem as follows: Given the allele-specific CNAs (copy numbers specific to each parental chromosome) of multiple clones and haplotype phasing (which alleles belong to each parental chromosome) both inferred from bulk DNA sequencing data, infer the clone label of each cell profiled by single-cell sequencing data. Here I describe two advances. First, we developed a probabilistic inference method Copy-typing to solve the single-cell clone inference problem. Copy-typing utilizes allele-specific CNAs and haplotype phasing to aggregate single-cell sequencing data across multiple chromosomes, and infer the clone labels via maximum a posteriori inference. Second, we made various improvements on existing allele-specific CNA inference methods using bulk DNA sequencing data to infer more accurate haplotype phasing and allele-specific CNAs. We validated Copy-typing on multiple real datasets. Our result shows strong agreement with orthogonal validation data. Using spatial transcriptomics data, Copy-typing identified spatially contiguous tumor clones which were consistent with pathology images and published analyses. Reading List: https://docs.google.com/document/d/1Okg8ke948Wj1oqMnOufyObxVqZTcSboYYzRVZ_tF... Everyone is invited to attend the talk, and those faculty wishing to remain for the oral exam following are welcome to do so.