Tim Kosfeld will present his General Exam "Computational modeling and integration of ATAC-seq" on Wednesday, January 28, 2026 at 12:00 PM in Bendheim House 103.

Committee Members: Yuri Pritykin (advisor), Ben Raphael, Ellen Zhong

Abstract:

Assay for transposase-accessible chromatin with sequencing (ATAC-seq) has been widely used at single-cell (scATAC) and bulk levels 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 ATAC-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 a program to quickly and efficiently scrape, compile, and preprocess this data from online sources. These atlases improve per-nucleotide accessibility prediction in ATAC-seq through ChromBPNet and uniquely capture spacing preferences for known transcription factor complexes. Allowing a better understanding of transcription factor activity in accessible regions.

Reading List:

https://docs.google.com/document/d/1gnqGszJkHUIQisI3UL_mw-w_pCR2hD0dmL5N5OACptM/edit?usp=sharing

Everyone is invited to attend the talk, and those faculty wishing to remain for the oral exam following are welcome to do so.