Researchers at Ny University’s Courant Institute of Mathematical Sciences have developed a novel algebraic model of DNA “hybridization,” a procedure central to many biotechnology devices that monitor alterations in cell’s gene expression or characterize a cell’s genome.
Their work, that is described in the journal Physical Review E, provides an additional tool for understanding how biological systems function and could enhance methods and designs of technologies utilized in cancer and genetics research.
Biology researchers seek to measure cell activity, but the task is really a challenging one due to the complexity — a cell has so many facets, all happening simultaneously, that it’s hard to measure the behaviour of their individual parts. Genes that do not necessarily affect each other in the cell can disturb each others’ measurements inside a biotechnology device.
To obtain around these obstacles, the NYU researchers focused on what sort of cell’s simplest components are measured — its DNA and RNA. Specifically, they used a cell’s gene expressions as a “tagging system” to watch cell behavior at its most fundamental level.
For this purpose, they centered on microarray technology in which researchers first gather data on the make-up of RNA molecules in two steps: RNA is first changed into cDNA, or “copy DNA,” after which measured by hybridization.
However, the researchers’ initial work involved not experiments, but, rather, the advance of mathematical models to calculate “DNA-cDNA duplex formation.” They developed an algebraic computation that allowed them to model arbitrary DNA-cDNA duplex formation, and, by using it, measurements of cellular behavior. Specifically, they assigned to various chemical properties of DNA strands different algebraic values (e.g., “K,” “X,” “Y”). They then ran a series of computations that led to expressing how “matches” or “mismatches” among various strands of DNA can be characterized by the input algebraic variables. These computations could then be used straight to design probably the most accurate biotechnology for measuring cellular behavior.
To confirm the validity of those algebraic models, they conducted laboratory experiments involving the hybridization of DNA sequences. These results largely confirmed those predicted by the mathematical models — the DNA sequences in the laboratory harmonized in most instances with techniques the models forecast.
The study’s co-authors were: Vera Cherepinsky, an old post-doctoral fellow at NYU’s Courant Institute of Mathematical Sciences and currently in the Department of Mathematics and Computer Science at Fairfield University; Ghazala Hashmi of BioArray Solutions, Ltd.; and Bud Mishra, a professor of computer science and mathematics and a principal investigator in Courant Bioinformatics Group.