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PacBio, Following Fast Behind Rivals, Seeks Answers for Germany’s E.Coli Outbreak

Xconomy San Francisco — 

Scary headlines about the E.coli outbreak in Germany have faded, but scientists are still looking to learn about the DNA sequence of this new bacterial invader, and how it evolved to become deadly. Super-cheap, superfast sequencing has made it easier than ever to dig into these kinds of questions, and today, researchers will have an interesting new set of data to pore over from machines made by Menlo Park, CA-based Pacific Biosciences (NASDAQ: PACB).

A global team of scientists, including researchers from PacBio, the University of Maryland, and Harvard Medical School, is reporting today that after sequencing the deadly strain of E.coli and comparing it with the sequences of 11 other strains, they were able to zero in on certain regions of the bacterial genome where mutations occurred that are thought to hvae made the new pathogen so dangerous. The findings are being published online today in the New England Journal of Medicine.

The German E.coli outbreak first came to public attention in late May, when news broke that 300 people had become seriously ill and 14 had died from the pathogen, which is usually far less virulent. Scientists, as usual, sprang into action to identify the bug and its source. Almost immediately, one German researcher, using a fast new tool from Carlsbad, CA-based Life Technologies (NASDAQ: LIFE), appeared to identify the virulent new strain of pathogen. That finding was quickly followed by sequencing information put in the public domain by BGI (formerly known as Beijing Genomics Institute).

The initial conclusions, though, had their limits, according to Eric Schadt, PacBio’s chief scientist. The initial reports about the pathogen were based on a comparison to just one E.coli genome as a reference in the public domain, leaving a lot of unanswered questions that PacBio and its collaborators felt could be tackled by sequencing a dozen different E.coli genomes, according to Schadt, a senior author on the new paper.

Eric Schadt

“This paper is important because it compares [the] outbreak strain to 11 others. It enables us to look at what were the regions that could have been responsible, or most important, for the increased pathogenicity or resistance of this particular strain,” Schadt says. “When you’re looking at comparing an outbreak strain to a single genome in the public domain, what can you really infer from that?”

PacBio came late to this scientific party, Schadt says, but it had reason to get in the game. Just as the outbreak struck, the company was in the midst of its all-important commercial introduction of its DNA sequencing machine. Given that it took $580 million of investment capital to get to that point, it would be an understatement to say that execution on its sales and marketing plan is a top priority.

But as followers of the company know, PacBio is hoping to carve out a niche for its novel sequencing technology in the world of infectious disease, so it stands to reason it could drum up sales by showing it is doing something useful in this field. The company made headlines last year when it showed that its machine was, in a matter of days, able to sequence a handful of different strains of cholera, which helped public health officials identify the source of a deadly outbreak last year in Haiti.

In this most recent case of the German E.coli outbreak, the PacBio instrument was able to generate sequences on each strain in about five hours, Schadt says. There was more work beyond that in analyzing the genomes, but the speed of the machine enabled PacBio and its collaborators to catch up with other scientific groups that had a head start using other machines, Schadt says.

PacBio’s instrument itself is high-priced at $700,000, but it can run simple experiments very fast and very cheaply-a basic question can be answered for as little as $99 and in as little as 30 minutes, the company has said. The machine in its current form is technologically different from others on the market, which PacBio and collaborators have learned has made it useful for infectious disease research. The PacBio machine can’t read a huge volume of DNA strands simultaneously, but it can read very long stretches of DNA. Scientists say that makes the instrument good at stitching together or “assembling” genomes for bacteria like E.coli which have much shorter overall genomes, than say, human beings.

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