The Future of Genome Sequencing

For the past decade, when a research community wanted to sequence the genome of their favorite species, they submitted a white paper to the National Human Genome Research Institute (NHGRI). Despite its name, the NHGRI funds genome sequencing projects of not only non-human mammals, but also non-mammalian animals and even non-animals (see here for a list). If a bunch of researchers want their species' genome sequenced, they would get together and explain why the genome should be sequenced. These should not be confused with typical research grant proposals that a principal investigator will submit to fund a research project.

I've been hearing rumors that the NHGRI is no longer accepting white papers for genome projects (I can't find anything on this at the NHGRI webpage). They will be shifting their focus toward other projects, including large scale polymorphism studies. Instead of white papers, grant proposals (submitted to NIH, I presume) will be required to fund whole genome sequencing projects. With the rapid decreases in the costs of whole genome sequencing, this won't be quite as absurd as it would have been a decade ago. A single proposal requesting a billion dollars to sequence a mammalian genome would be downright silly, but it's getting pretty darn close to affordable to propose a complete genome sequencing project with a single NIH grant.

Before I get into fun speculation, is there any truth to the rumor that the NHGRI won't be accepting genome white papers? If so, I've got some ideas on the (near) future of genome sequencing.


More like this

Well, someone at ScienceBlogs had to draw down on Scientopia, and it might as well be the Mad Biologist. I was going to respond to this post by proflikesubstance about genomics and data release in a calm, serious, and respectful manner, and, then, I thought, "Fuck that. I'm the Mad Biologist. I…
A couple of weeks ago I suggested that the National Human Genome Research Institute (NHGRI) would no longer be funding de novo genome sequencing projects via white papers. They appear to be shifting their focus to resequencing projects to study variation (ie, this) and take a closer look at well…
The genome of the Platypus has been sequenced: The first analysis of the genome sequence of the duck-billed platypus was published today by an international team of scientists, revealing clues about how genomes were organized during the early evolution of mammals. The research was supported in part…
Just got this exciting news by e-mail: Data on Equine Genome Freely Available to Researchers Worldwide BETHESDA, Md., Wed., Feb. 7, 2007 - The first draft of the horse genome sequence has been deposited in public databases and is freely available for use by biomedical and veterinary researchers…

I don't know if that will be a formal policy, but they're already moving in that direction by sending more and more of the money to the major sequencing centers. Another shift in focus is a move towards downstream applications. I think the feeling is that genomics 'revolution' hasn't done as much as it could have (or at least needs to become more focused). Also, there's a move towards larger projects (i.e., more genomes per project).

That's what I hear anyway when I talk to people doing and funding genomics.

I don't know about NHGRI specifically but from what I have heard from some of the big sequencing centres the days of whole genome sequencing are coming to an end (within 1-2 years) and the sequencing infrastructure will be re-purposed to reequencing projects. The dollars for whole genomes don't seem to be there, despite falling costs.

the days of whole genome sequencing are coming to an end

I also don't know about NHGRI (and their website is not that up to date). But I'd be surprised if the above statement were true. The JGI for instance have a very active sequencing program. I was told that one of their aims is to generate high-coverage sequences for 6000 microbial taxa. Human-health related genomics may not be delivering on its promise but lots of other projects are.

I haven't heard anything from the NHGRI, but it's no secret that the priorities in all three of the major genome centers are shifting to resequencing projects. There will still be some sequencing of new organisms, but those pipelines are so fast and so well established that they're hardly even news any more. (How much press did the sea urchin genome get?)

Last I heard, a human genome is going for around $500k, and as pyrosequencing and Solexa technologies take off, the cost is going down considerably. If they aren't already, sequencing new organisms will be well within an NIH grant in a year or two.

As you said, the big push now is to identify genomic variation, so that disease loci can be identified and eventually, the 'era of personalized medicine' can be ushered in. The Cancer genome project is just launching, and there's talk of a Human Variome Project, which is a little more amorphous at the present.

I'm probably a bit biased by my research focus, but it seems sensible that the NHGRI research money is being funneled to the cutting edge stuff, rather than towards cranking out more new genomes that won't have much immediate application. From a biomedical perspective, it makes more sense to sink the big bucks into that are likely to have clinical applications in the relatively near future. I have little doubt that sequencing companies and spare pipeline cycles will easily be able to produce the novel sequences that people ask for.

(cross posted at my site)

I was told that one of their aims is to generate high-coverage sequences for 6000 microbial taxa.

I just wish that not just sequencing, but gap closure would also benefit from some cost breakthrough. While I think it's great that the JGI and others are coming out with lots of microbial genomes, in general these genomes aren't really closed. It's understandable why -- as sequencing gets cheaper, closure becomes a larger and larger fraction of the budget of a genome project, and it's tempting just to be satisfied with a bunch of semi-assembled contigs, perhaps stitched together into a pseudomolecule. But without closure, interpreting the data as anything besides a collection of genes is impossible, as genomic structure is lost.

I just wish that not just sequencing, but gap closure would also benefit from some cost breakthrough

Oh, I second that. My last group was stuck with a draft for four years before closure. It was good for some things - identifying MS/MS peptides for instance and gave us some idea of general metabolic capability, but it's hard to write the killer paper without a closed genome. Mind you, those big papers about eukaryotic genomes are all based on unfinished sequence too aren't they?

Gap closure needs some technological breakthrough as well as a cost one. It's incredibly slow and tedious at the moment, getting a few hundred more bases at a time, reassembling, running through consed, iteratively.

Mind you, those big papers about eukaryotic genomes are all based on unfinished sequence too aren't they?

Oh, absolutely. As even closing prokaryotic genomes is a pain, those eukaryotes, all filled with repeats as they tend to be be, would be prohibitive. I remember the first time I wanted to look at the human genome and naively thought that one could just download a FASTA file of each chromosome...

My hope is that commercial genome sequencing will drive down the price so much that in just a few short years a lab can have their favorite genome sequenced for the price of some other popular types of analysis (like a few mass spec samples, for example). Although there might not be a huge commercial demand for the genomic information of bacteria, there is/would be a huge demand for an individual's genomic information. This demand will be the driving force behind new technologies that make sequencing affordable. What do you think?

And by the way, as another member of the DNA Network, I look forward to some great conversations!

Microbial genome sequencing is funded by the NSF and the DOE, not by NHGRI

Yes, I know. I was citing JGI to express doubt that the days of whole genome sequencing are coming to an end, not in reference to NHGRI.