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One Molecule at a Time

The ability to study single molecules has enabled researchers to peer into their inner workings and how they interact with other molecules, writes Harvard University's X. Sunney Xie in the Journal of the American Medical Association this week.

For instance, he writes that single-molecule study of turnover oxidase, a cholesterol enzyme, has underscored that single-molecule chemical reaction are stochastic, rather than deterministic, as they appear when a greater number of molecules are studies.

As DNA is present as single molecules as chromosomes in cells, Xie notes that changes to it, too, are stochastic, necessitating the need for single-cell genomics.

Currently, much of single-cell genomics relies on MALBAC — multiple annealing– and looping-based amplification cycles — to amplify the genome to more easily detected level, a method developed by Xie and his colleagues. This method, he writes, has been applied to in vitro fertilization procedures as well as cancer diagnoses. It allows scientists to determine the copy number of genes and single nucleotide variations.

"The ability to count the copy numbers of a gene and detect a point mutation in a single cell is now not only possible, but is critically important as well," Xie adds. "Such single-molecule methods have allowed for probing, understanding, and bettering life at the single-molecule level and provided a tangible example of precision medicine."