Next Generation DNA Sequencing

Scale, proportion, and quantity belong to one of the cross cutting concepts in the next generation science standards (NGSS).  According to Volume 2 of the NGSS, "in engineering, no structure could be conceived much less constructed without the engineer's precise sense of scale."  The authors go on to note that scale and proportion are best understood using the scientific practice of working with models. When scientists and engineers work with these concepts at a molecular scale, new kinds of technologies can be created to advance our understanding of the natural world. One example is DNA ... Read more
Getting an accurate genome sequence requires that you collect the data at least twice argue Robasky, Lewis, and Church in their recent opinion piece in Nat. Rev. Genetics [1]. The DNA sequencing world kicked off 2014 with an audacious start. Andrew Pollack ran an article in the New York Times implying that 100,000 genomes will be the new norm in human genome sequencing projects [2]. The article focused on a collaboration between Regeneron and Geisinger Health in which they plan to sequence the exomes (the ~2% of the genome that encodes proteins and some non-coding RNA) of 100,000 individuals ... Read more
In simple Mendelian genetics, a single change in one gene can produce a large change in mortality. The National Human Genome Research Institute (NHGRI) will be funding genomics studies on Mendelian traits using a similar strategy. NHGRI will fund a small number of centers, dominant centers you might say, and look for large changes. The sequencing centers that will benefit are the Broad Institute, Washington University, and Baylor College of Medicine. For the next four years, the big three will be dividing $86 million a year according to a press ... Read more

For the past few days I've been avidly following Daniel MacArthur's tweets from the Personal Genome Conference at Cold Spring Harbor(@dgmacarthur #cshlpg).

The Personal Genomics tweets aren't just interesting because of the science, they're interesting because MacArthur and others have started to take on the conventional dogma in genetic ethics.

For years, there has been a strong message from the clinical genetics and genetics education community that genetic information is dangerous.

... Read more

I had the good fortune on Thursday to hear a fascinating talk on deep transcriptome analysis by Chris Mason, Assistant Professor, at the Institute for Computational Biomedicine at Cornell University. 

Several intriguing observations were presented during the talk.  I'll present the key points first and then discuss the data.

These data concern the human transcriptome, and at least some of the results are supported by  follow on studies with data from the pigmy tailed macaque.

Some of the most interesting points from Mason's talk were:

  1. A large
  2. ... Read more
These days, DNA sequencing happens in one of three ways. In the early days of DNA sequencing (like the 80's), labs prepared their own samples, sequenced those samples, and analyzed their results. Some labs still do this. Then, in the 90's, genome centers came along. Genome centers are like giant factories that manufacture sequence data. They have buildings, dedicated staff, and professional bioinformaticians who write programs and work with other factory members to get the data entered, analyzed, and shipped out to the databases. (You can ... Read more

You might think the coolest thing about the Next Generation DNA Sequencing technologies is that we can use them to sequence long-dead mammoths, entire populations of microbes, or bits of bone from Neanderthals.

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Last spring, I gave my first hands-on workshop in working with Next Generation Sequencing data at the Eighth Annual UT-ORNL-KBRIN Bioinformatics Summit at Fall Creek Falls State Park in Tennessee. The proceedings from that conference are now on-line at BMC Bioinformatics and it's fun to look back and reflect on all that I learned at the conference and all that's happened since.

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A couple of years ago, I answered a reader's question about the cost of genome sequencing. One of my readers had asked why the cost of sequencing a human genome was so high. At that time, I used some of the prices advertised by core labs on the web and the reported coverage to estimate the cost of sequencing Craig Venter's genome. As you can imagine, the cost of sequencing has dropped quite a bit since then.

In 2007, Genome Technology reported the cost of sequencing ... Read more

Watching the chIPs roll in, then I watch them roll away again, I'm just sitting on the DNA, wasting time (sung to the tune of "Sitting on the dock of the bay" by Otis Redding) Hesselberth recently published a paper about digital genomic footprinting that blew me away because it has so much potential. The authors used DNAse I and Next Generation DNA Sequencing to map every site in the yeast genome where a protein might be sitting. Since I used to do similar kinds of experiments, albeit on a much, much smaller scale, this sort of publication boggles my mind. ... Read more

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