Fine-Scale Genome Folding Relative to Transcription and Location

ABSTRACT This supplement will train a talented and high potential PhD student, Tim Reznicek, in critically needed high- demand areas of bioinformatics and data analysis. Under the parent award, we proposed tracking transcription relative to 3D genome folding as well as to develop tools that improve the analysis of genome-wide chromatin organization assays. This supplement will support Tim’s training within a Bioinformatics & Systems Biology PhD program to learn algorithm / software development, as well as the analysis of complex 3D genomic datasets. The provided research plan includes details on the development of JukeBox, a tool which this student will develop to measure, filter, and normalize noise in massive chromatin conformation matrices. We also include aims to use serum stimulation for transcription synchronization, along with auxin-mediated acute degradation of Integrator subunits, to investigate the coordination of transcription and the sub-genic 3D genome folding. These aims address an intriguing and high-profile topic in the field of genome architecture, by answering once and for all, which comes first: transcription or looping? As part of this research, the student will gain training and experience in algorithm and software development, version control, maintenance, benchmarking, and implementation. Tim will also be trained in hypothesis-driven bioinformatics, multi-‘omic data integration, and the analysis of large complex 3D genome datasets. To facilitate Tim’s career, we have added a co-mentor structure, with Drs. Rowley and Cummings, as well as supervisory committee members, who will support the candidates research and career development activities, including presentation at conferences, interactions with the ENCODE community, manuscript / grant writing, as well as leadership development experiences.