Short Read Sequencing Not Up to the Task of Characterizing Transcriptome Says Mike Snyder of Stanford


Mike Snyder, Director, Center for Genomics & Personalized Medicine, Stanford Bio and Contact Info

Listen (5:44) Current method for figuring out transcriptomes is crazy

Listen (4:18) Long reads necessary to find paternal or maternal alleles

Listen (4:31) Practical applications of the transcriptome

Listen (4:41) Has the race to the $1,000 Genome been at the expense of quality?

Listen (6:33) If price drops for long reads is there a future for short reads?

Today we launch the much anticipated series on The Rise of Long Read Sequencing with Mike Snyder, Chair of Genetics at Stanford. Mike has been working four years on what has become known as the “Snyderome” (or "Narcissome" as his colleagues call affectionately call it), looking at hundreds of thousands of his own molecular biomarkers regularly over time. Lately Mike has been focused particularly on his transcriptome, or RNA molecules.

The transcriptome is studied by looking at individual isoforms. On average, every gene has five or six isoforms or transcripts. Recently Mike has co-authored a couple papers showing that it is difficult to identify full-length transcript isoforms using the current short read sequencing technology.

“The way we figure out transcriptomes now is kind of crazy if you think about it," he says. "We take RNA. We blow it up into little fragments, and then we try to assemble them back together to understand what the transcription looked like in the first place. That’s a horrible way to do this.”

Mike explains how PacBio's long read technology is opening up new possibilities for characterizing the transcriptome and identifies some of the practical applications that might come from his research.

So what does this mean about the future of NGS? If PacBio or one of the emerging nanopore sequencing companies can offer long reads at high throughput, is there any reason why a researcher would use short read technology?

"If the long reads are high quality and cheap, you wouldn't need the short reads. . . [long reads] would take over the market." Mike says.

Reflecting on the rapid changes we've seen in the NGS space from year to year, he says, "next year we'll probably have a whole different conversation."

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