High-density Genome Maps and Its Applications

Friday, February 23, 2024

1:00 PM-3:00 PM

BIOMED PhD Research Proposal

Title:
High-density Genome Maps and Its Applications

Speaker:
Yilin Wang, PhD Candidate
School of Biomedical Engineering, Science and Health Systems
Drexel University

Advisor:
Ming Xiao, PhD
Professor
School of Biomedical Engineering, Science and Health Systems
Drexel University
 
Details:
We propose to generate high-density whole genome maps in nano-channels by combining Cas9- guide-RNA (gRNA) sequence-specific DNA labeling and motif-based DNA labeling. Cas9-guide- RNA (gRNA) DNA labeling uses the mutant Cas9 proteins to fluorescently label almost any 20mer+NGG (PAM) across the human genome, especially the repetitive sequences that are inaccessible to traditional motif-based labeling methods. In combination with single-molecule long sequencing reads, we aim to address two critical challenges in genome analysis: de novo haplotype-resolved genome sequence assembly and whole genome structural variation analysis.

In my proposal, I will outline the use of informatics pipelines to achieve specific goals. First, the pipelines will assemble long DNA molecules into consensus contigs with motif-based labels. Then, they will map Cas9-guide-RNA (gRNA) sequence-specific labels of individual DNA molecules to form consensus Cas9-labeling locations on the contigs. The pipeline will then search for on-target and potential off-target labeling by sgRNA probes, which is crucial for selecting suitable sgRNAs and determining haplotypes. My pipeline will also combine different gRNA- labeled samples to generate high-density and haplotype-resolved genome maps. Finally, by combining Cas9-assisted high-density mapping with just 30x coverage of PacBio HiFi reads, we will be able to assemble phased genomes with 90% coverage of the human genome and perform comprehensive genetic variation analysis.

Contact Information

Natalia Broz
njb33@drexel.edu