Measurements of DNA barcode label separations in nanochannels from time-series data.

We analyzed time-series data for fluctuations of intramolecular segments of barcoded E. coli genomic DNA molecules confined in nanochannels with sizes near the persistence length of DNA. These dynamic data allowed us to measure the probability distribution governing the distance between labels on the DNA backbone, which is a key input into the alignment methods used for genome mapping in nanochannels. Importantly, this dynamic method does not require alignment of the barcode to the reference genome, thereby removing a source of potential systematic error in a previous study of this type. The results thus obtained support previous evidence for a left-skewed probability density for the distance between labels, albeit at a lower magnitude of skewness. We further show that the majority of large fluctuations between labels are short-lived events, which sheds further light upon the success of the linearized DNA genome mapping technique. This time-resolved data analysis will improve existing genome map alignment algorithms, and the overall idea of using dynamic data could potentially improve the accuracy of genome mapping, especially for complex heterogeneous samples such as cancer cells.

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