New method reveals how the genome is regulated and disrupted in diseases

Researchers at the University of Minnesota Medical School have developed a new method called PARTAGE that provides a clearer picture of how the genome is regulated and disrupted in diseases like cancer. The findings were recently published in Genome Research.

PARTAGE allows researchers to measure three key features of the genome from the same sample: when DNA is duplicated, changes in DNA copy number, and gene activity. Traditionally, these processes have been studied in separate experiments, making it harder to understand how cells coordinate these processes. 

"PARTAGE lets us connect DNA replication, genomic alterations and gene activity in a single experiment - giving us a more complete view of how the genome is regulated and how it is altered in disease, like in cancer cells," said Juan Carlos Rivera-Mulia, PhD, an assistant professor at the University of Minnesota Medical School and principal investigator of the study. "This work could help identify new biomarkers and uncover potential therapeutic targets." 

Researchers found that PARTAGE produces results just as accurate as current gold-standard methods performed separately. The method also shows a strong link between early DNA replication and active gene expression, and precisely detects genome alterations, such as extra or missing pieces of DNA in cancer cells. Looking ahead, researchers plan to apply PARTAGE to cancer models. 

The research was funded by the National Institutes of Health and National Institutes of General Medical Sciences [R35GM137950, R35GM137950-02S1, and R35GM137950-04S1], Regenerative Medicine Minnesota [RMM-091621-DS-006] and the University of Minnesota Medical School. The study was led by co-first authors Lakshana Sruthi Sadu Murari and Quinn Dickinson, with contributions from former postdoctoral researcher Silvia Meyer-Nava.