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In a new paper in Genome Research, Yuval Ebenstein’s team at Tel Aviv University presents an impressive way to label genome wide methylation on Bionano. Yuval, professor in the Department of Chemical Physics, was our very first Bionano customer. He picked up an early version of our Irys instrument on his way to Tel Aviv, and has put it to good use ever since in his NanoBioPhotonix Lab.  He recently purchased Saphyr to take his work to the next level.

The image you see on top of this post is that of DNA methylation labeled and imaged on a Bionano system as described in the paper. It’s a clever trick of engineering, in which they tricked a methyltransferase to attach a fluorescent dye when there’s no CpG methylation in its recognition sequence. Bionano’s NLRS labeling is used with a red dye to allow for identification of the molecules and for assembly of the genome.

As a result, we can now read the methylation status of the genome on long, single molecules while simultaneously mapping major structural variation on the same molecules. In the image above, you see a green signal repeat every 50 kbp – this is an unmethylated CpG island in a 50 kbp repeat.

This technology opens up an entirely new field of research: we can now study if the methylation status of the promotor of a gene influences that of another promotor hundreds of kbp away on single molecule. If you’ve ever worked with bisulfite converted DNA, you know that this is no small feat. This paper is mostly a proof of concept, but we can’t wait to see what you will do with this technology in your research.

An older paper from Yuval’s team that’s worth pointing out was discussed at length in an interview on the Mendelspod Podcast, where he described single molecule imaging as the “middle way” between NGS and cytogenetics. Here, Yuval’s team uses Cas9 to cut a 200 kbp fragment out of genomic DNA, isolates it using pulse-field electrophoresis, and then puts that gel fragment back into the standard Bionano DNA prep and labeling. The result is a highly enriched sample that can be mapped with Bionano or sequenced. Bionano mapping is typically done on a whole genome scale, but this method could allow you to map a region of interest much faster.

Just like the origin of replication mapping we discussed previously, methylation mapping is not an application we support commercially, but we are grateful for scientists like Yuval who push the boundaries of what a Bionano instrument can do!


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