Tim Kosfeld will present his General Exam "Advances in Supervised Interpretation and Preprocessing of ATAC-seq" on Tuesday, May 27, 2025 at 12:00 PM in Icahn 101. Committee Members: Yuri Pritykin (advisor), Mona Singh, Ben Raphael Abstract: Single-cell assay for transposase-accessible chromatin with sequencing (scATAC-seq) has been widely used to profile chromatin accessibility and explore the epigenomic properties in heterogeneous cell populations. Furthermore, transcription factors (TFs) bind to accessible sites, and scATAC-seq analysis could associate TF binding specificities, typically available as sequence motifs, with variance in chromatin accessibility. Here we present a new supervised TF motif regression method, MotifReg, for computational analysis and interpretation of scATAC-seq data. MotifReg can efficiently analyze large-scale scATAC-seq datasets and learn interpretable associations between TF motifs and accessible peaks. The resultant low-dimensional cell representations in the TF activity space facilitate downstream cell type-specific analyses of scATAC-seq data. The supervised formulation in MotifReg enables ranking TF motifs by significance of their association with chromatin accessibility, implicating cell type-specific TFs. Furthermore, by comparing MotifReg performance across data analysis settings, we develop guidelines and best practices for scATAC-seq peak calling, data preprocessing and normalization. We leverage these best practices to show that aggregation of biologically similar ATAC data allows for the discovery of chromosomal regions enriched for chromatin interaction, known motif binding, or ATAC co-accessibility. We provide an automated methodology to quickly and efficiently scrape, compile, and preprocess this data from online sources and illustrate how construction of these high-quality atlases can complement existing analyses. Reading List: https://docs.google.com/document/d/1gnqGszJkHUIQisI3UL_mw-w_pCR2hD0dmL5N5OAC... Everyone is invited to attend the talk, and those faculty wishing to remain for the oral exam following are welcome to do so.