Mathematics enables scientists to understand organization within a cell’s nucleus
Indika Rajapakse, Ph.D., latest development is a new mathematical technique to begin to understand how a cell’s nucleus is organized. The technique, which Rajapakse and collaborators tested on several types of cells, revealed what the researchers termed self-sustaining transcription clusters, a subset of proteins that play a key role in maintaining cell identity.
They hope this understanding will expose vulnerabilities that can be targeted to reprogram a cell to stop cancer or other diseases.
The paper is published in Nature Communications. The project was led by a trio of graduate students with an interdisciplinary team of researchers.
The team improved upon an older technology to examine chromatin, called Hi-C, that maps which pieces of the genome are close together. It can identify chromosome translocations, like those that occur in some cancers. Its limitation, however, is that it sees only these adjacent genomic regions.
The new technology, called Pore-C, uses much more data to visualize how all of the pieces within a cell’s nucleus interact. The researchers used a mathematical technique called hypergraphs. Think: three-dimensional Venn diagram. It allows researchers to see not just pairs of genomic regions that interact but the totality of the complex and overlapping genome-wide relationships within the cells.
The researchers tested their approach on neonatal fibroblasts, biopsied adult fibroblasts and B lymphocytes. They identified organizations of transcription clusters specific to each cell type. They also found what they called self-sustaining transcription clusters, which serve as key transcriptional signatures for a cell type.
