The OpenHelix Blog

Welcome to our Friday feature link dump: SNPpets. During the week we come across a lot of links and reads that we think are interesting, but don’t make it to a blog post. Here they are for your enjoyment…

• Idle computers for active research: read the article from GenomeWeb. [Jennifer]
• NAR Annual Web Server issue for 2010 is out. [Mary]
• Francis Collins: the extended genome anniversary interview covers regulation of personal genomics, the sequencing of children’s genomes, cancer, pharmacogenomics, and more. [Mary]
• Symphony of life: making music out of the human genome, a performance of DNA as music called Allele to be performed next month. [Mary]
• modENCODE data now available in WormBase. [Mary]
• OMG. You have to hear Paul Nurse describe his genealogy: Family Trees are Dangerous.  I’m amazed. And I’m wondering how it would have gone if he’d had his + his family’s genomes sequenced instead of the way it played out. From The Moth and heard last night on my local NPR station, found the audio here. [Mary]  PS: the process of the Green Card is additionally amusing–he was rejected first, despite knighthood + Nobel Prize. Snorf.

The last tip of the week I did was Genome Variation Tour I where we started our journey following one SNP in an individual’s genome through various databases to see what we can find out about that variation. In that tip we started out by looking at a SNP in the CYP4F2 gene in the UCSC Genome Browser and followed it to dbSNP. Today’s tip will continue our journey to OMIM to see what information we can find there. We’ll find this variation is clinically associated with Warfarin dosage effects and specifically this individual’s C/T heterozygosity indicates an intermediate dosage for effectiveness if indeed he ever needed this drug.  In some ways, your guess is as good as mine as to what we will find and what avenues we will be taking in the next few tips I’ll be doing. I’m am discovering information as I go along too. I can tell you though that the next installment of the genome variation tour will take us to PubMed, and a few not particularly well known but gem databases perhaps and probably back to the UCSC Genome Browser to expand our look at the interactions of several variations in this individuals genome.

Illumina announces that they are slicing their price of whole-genome sequence to 19,500 . This is half what they were charging before. Hey, you can get it at 14,5000 per genome if you do it in bulk, 5 or more people. Perhaps you and your family for a cool 72,500?

As I mentioned before, the price of personal genome sequencing has been plummeting and I predicted 1,000 by the end of a year’s time. Admittedly, that is a bit (understatement) of an optimistic prediction, but the trajectory definitely is headed that way.

Comprehensive tutorial on the publicly available GeneTests resource enable researchers to quickly and effectively use this invaluable resource.

Seattle, WA (PRWEB) May 25, 2010 – OpenHelix today announced the availability of an updated tutorial suite on GeneTests.

GeneTests is an integrated resource designed to provide access to current genetic testing and other clinical genetics information. The GeneTests resource includes the Laboratory Directory database, an international directory that identifies the location of clinical laboratories offering genetic testing; and GeneReviews, a collection of up-to-date, comprehensive disease-specific overviews which include clinical descriptions, diagnosis, management, molecular genetics, current genetic testing, and genetic counseling. This tutorials, in conjunction with OpenHelix tutorials on OMIM, dbSNP, GVS, HapMap and many others will give the medical researcher or clinician a set of training resources to help be efficient and effective at accessing and analyzing genomic variation and biomedical data.

The tutorial suites, available through an annual OpenHelix subscription, contain an online, narrated, multimedia tutorial, which runs in just about any browser connected to the web, along with slides with full script, handouts and exercises. With the tutorials, researchers can quickly learn to effectively and efficiently use these resources. The scripts, handouts and other materials can also be used as a reference or for training others.

This tutorials will teach users:
*to perform disease-specific searches and navigate the GeneTests site
*to understand the GeneReviews and Laboratory Directory Displays
*to access additional searches to query the GeneReviews and Laboratory Directory databases by disease feature, gene and protein specific searches, and more
*to identify U.S. and international laboratories offering molecular genetic testing for specific disorders, use the Clinical Directory to locate genetics professionals and services, and investigate additional educational and other resources

To find out more about these and over 90 other tutorial suites visit the OpenHelix Catalog and OpenHelix. Or visit the OpenHelix Blog for up-to-date information on genomics and genomics resources.

About OpenHelix
OpenHelix, LLC, (www.openhelix.com) provides a bioinformatics and genomics search and training portal, giving researchers one place to find and learn how to use resources and databases on the web. The OpenHelix Search portal searches hundreds of resources, tutorial suites and other material to direct researchers to the most relevant resources and OpenHelix training materials for their needs. Researchers and institutions can save time, budget and staff resources by leveraging a subscription to nearly 100 online tutorial suites available through the portal. More efficient use of the most relevant resources means quicker and more effective research.

I’ve mentioned before that personal genomics seemed to have hit a tipping point. Some of the evidence of that seems to be that the FDA and other regulatory agencies have taken a heightened interest in mass-market gene and genomics tests.

That is going to be the next step in our progress towards personal genomics and medicine, and one that if done right will make this part of our history a successful one. To that end, the Genomics Law Report has an interesting post: “Transparency First: A Proposal for DTC Genetic Testing Regulation.” His argument, make the registry mandatory, make transparency mandatory, is a good start.

There is also a debate going on (which I’m going to be a fence-sitter on for now) on whether the FDA should be governing these ‘Direct to Consumer’ tests. Decisiontree says no:

The controversy seems to have stirred the FDA to assert its authority – and that of physicians – over any and all medical metrics. As readers of The Decision Tree know, I have little patience for the argument that we need doctors as gatekeepers of our genetic information. This isn’t a drug, and this isn’t a device – it’s information about ourselves, as ordinary as our hair color or our waist size or our blood pressure – all things that we can measure and consider without a doctor’s permission.

Gene Sherpa says they got it all wrong:

This is not about getting access to your data.

Fine, you want a whole genome, go get it!

The FDA is not asking should people be able to go out and buy this. It is asking several other questions.

1. Is Interpretation of biometric data considered medicine?

2. Is DTCG analyzing biometric data and intending to give an interpretation of that data which indicates a disease a person has?

3. Should we regulate a system which has not given indication of their quality control if they are indeed intending to provide medical diagnosis?

4. Are these methods of obtaining human samples to derive biometric data for the intent of analyzing and providing information about disease considered medical devices?

All three are interesting and informative reads. Just thought I’d point them out. (hat tip on those last to to Daily Scan).

Welcome to our Friday feature link dump: SNPpets. During the week we come across a lot of links and reads that we think are interesting, but don’t make it to a blog post. Here they are for your enjoyment…

• Go play fold.it and fold some proteins as a game! [Trey]
• In a counterpoint (though actually I agree to an extent) to my post Tuesday, Newsweek writer thinks personal genomics is over-hyped. Though I do think this is making a judgement before the fat lady sings , declaring failure before completion [Trey]
• Might be an interesting bioinformatic read:  “Bioinformatic analysis of CaBP/calneuron proteins reveals a family of highly conserved vertebrate Ca²⁺-binding proteins.” by McCue , Haynes  and Burgoyne – free from BioMed Central  [Jennifer]
• VIVO Conference: Enabling National Networking of Scientists, will bring together scientists, developers, publishers, funding agencies, research officers, students and those supporting the development of team science. Registration now open. [Mary]
• “NCBI has a YouTube channel currently populated with videos from GenBank’s 25th anniversary: http://www.youtube.com/ncbinlm ” [Mary]
• Making progress towards the Camel genome:  “Sequencing, Analysis, and Annotation of Expressed Sequence Tags for Camelus dromedarius”. See the data at CAGBASE. I’m pretty sure that’s the first Saudi database I ever looked around in. [Mary, hat tip to Coturnix]

Today’s tip of the week is actually the first in a series of tips I will be doing over the next couple months. The recent paper in Lancet did a clinical assessment of an individual genome. In doing so, the researchers used various genomic resources do ascertain and interpret the data. We have a free tutorial on NIEHS SNPs that walks through some of these resources, but I thought it might be useful to follow one specific nucleotide variation through a lot more genomic databases to show the user what data is available and how to access it. Each tip I do over the next couples months (not every week, I do tips every 2-3 weeks) will follow a specific SNP through the databases. In this case, rs108622 in the CYP4F2 gene (cytochrome P450, family 4). These tips aren’t for the genome jockey’s and SNP surfers among us, they are more an introductory tour of what’s out there. They will be useful for those just starting to look at genomic variations, medical practitioners, clinicians or those just curious what is available. Today’s tip will start with the UCSC Genome Browser, find the variation and follow it through to dbSNP. Next tip will look closer at the dbSNP information and then follow the trail to OMIM and GeneTests. In later tips we’ll take the variation to another 4-6 different databases and genomic variation resources from HapMap and others. In the posts themselves I’ll link to even other variation databases. There is a plethora of them.

Please indulge a long post from a personal perspective, what genomics is about to do for _me_. This is information that many, if not all, of our readers already know. I’ve been researching and working in either experimental biology or genomics for over 20 years. Ever since the beginning of the Human Genome Project , which coincidently started the same year I started my Ph.D. program, into my postdoctoral research at EMBL and now my work at OpenHelix, I’ve known that someday personal genomics was going to impact me, and millions of others, in a big way. Yet, it has always felt that it was one of those things that would be a decision I and we as a society didn’t have to make until we turned that corner that seemed always “just ahead.”

But now I think we’ve turned a corner. It feels, to mix metaphors, that we’ve hit a tipping point. The Human genome project, the mapping and sequencing of the/a human genome from 1990 to 2003, cost approximately 2,700,000,000 dollars (that’s 2.7 billion, I wanted to get all the zeros in). Celera did the genome for 300,000,000. The cost of sequencing an entire human genome has been plummeting ever since. In 2007, the cost of sequencing the genome of James Watson (co-discoverer of DNA) was about 2,000,000. The today cost is about 10,000. Complete Genomics and other companies are on the march to quickly reducing the cost of sequencing a genome under 1,000.

Let me graph the last 8 years for you, mind you, this is starting from the 300,000,000 number, not the 2.7billion, because that graph would be a straight line down.

So, within a year, the cost of sequencing your, my, genome will reach 1,000. If not less. We’ve seen this coming for years now, and it’s upon us. But what does it mean?  A lot of data. But data means nothing without context and analysis. Sequencing my genome would be a waste of 1,000 dollars if I gleaned nothing from it.

Yet, even that seems to have turned the corner from a few tidbits of genetic information to a steady steam and the beginning of a flood.

You know you’ve turned a corner when a genomics testing company begins to offer genetic tests to the mass market through Walgreens. There’s enough context in that data to make money from it, or so they hope. You can be sure the corner is safely behind you when the FDA tells Pathway Genomics and Walgreens that they will need to hold off while they make sense of the regulatory implications. Genomic ancestry test are are also gaining is usability… and scrutiny.

It was the recent Lancet paper on the clinical analysis that seemed to be a tipping point, not for me or those in the field. Genomics has been on my radar since 1988, but for society. I blogged about the paper and it’s use of genomics resources such as GVS, dbSNP and others. In the paper, the researchers did a thorough clinical assessment of an individual’s genome. We’ve brought down the cost of sequencing, now we are learning how much it’s going to take to assess that data from a medical point of view, and importantly, what we can learn from it.

What can we learn from it? I read this paper again from a personal perspective now. Could I learn something from sequencing and analyzing my genome, and if so what. My answer came to this: yes, I could learn something and in fact enough that I’m not convinced that as soon as that sequencing gets down to a 1,000 or lower (and is a high quality sequence , I’m going to do it.

There are three things I see from this paper that one could learn from assessing their genome: prevention, early detection and therapy. I believe the former will be, for most people, something they already know and their genome sequence will tell them nothing new. The other two could be a wealth of information they will want, even need, to know. You’ll notice I left off ‘cure.’ I saw nothing in this paper, and nothing on the near horizon, that suggests to me that our genome sequence data will help with curing anything. Perhaps, just not much. Yet, the possibilities of early detection of disease and personalized drug treatment are tantalizing.

Welcome to our Friday feature link dump: SNPpets. During the week we come across a lot of links and reads that we think are interesting, but don’t make it to a blog post. Here they are for your enjoyment…

• If you are on the coding end of things in Bioinformatics, you might want to take a look at Yokofakun, a bioinformatics blog [Trey]
• If you want to see a hilarious take-down of junk science in medicine:
  
  That’s from the Brits Mitchell and Webb, if your vegetarian you might not want to watch this .  [Trey]
• The buzz of the personal genomics twittosphere this week was this terrific article at Genomics Law Report, by Dan Vorhaus: Mapping the Personal Genomics Landscape [Mary]
• The bunny browser hops along!  European Rabbit Genome Browser released at UCSC Genome Browser [Mary]
• I think this is interesting to think about, but not sure which I am: Evolution of science from Lauren Urban at the The Scientist.com [Jennifer]

• Not the penguin you think it is: Comparative Functional Genomics: Penguin vs. Bacterium at Byte Size Biology. Things that make you go: huh. I always figured binary was too limited since we run on 4 bases, now it looks like programming is backwards. [Mary]

• For those of us who have had research papers reviewed, just a bit of humor. [Trey]

The Lancet paper, Clinical assessment incorporating a personal genome, has held my fascination this weekend (yes, I read it at the beach). Mary posted Friday and again Saturday on the paper and related NPR segment. It feels to me to be a seminal paper, though I do agree with Daniel at Genetic Future, there are a lot there we still don’t know. A large portion of the variation is in non-coding regions, and thus predictions and propensities are hard to come by with the available analysis. In fact, as he pointed out, many of the coding region variations have little information as to their effect on disease. I would add also that even if we get to that holy grail of $1,000 to sequence a personal genome, this kind of extensive analysis would still be time and cost-prohibitive for the vast majority of sequenced genomes.

Yet, as with all early steps in science and medicine, there’s missing pieces, large gaps and huge efforts (think “space travel,” “computers,” “microwave ovens,” “internet,”) that over time become inexpensive and commonplace (ok, so the former isn’t necessarily “inexpensive”). Sequencing genomes will become inexpensive before the analysis does, but both will come. And I think this paper is pointing to that future.

The other hurdle to large scale personal genomics I see (of course) is the understanding and use of the genomics and data resources. The authors use a large (and excellent, in my opinion) suite of genomics resources to do obtain data and do their analysis. I’ll list them here with links in alphabetical order:

dbSNP (T)
GVS (T)
HapMap (T)
HGMD
OMIM (T)
PharmGKB
PolyPhen
PubMed (T)
SIFT
UniProt (T)

All of these resources have a wealth of data, but even then, that is a lot of analysis and familiarization that is needed with each tool. Each tool does have documentation and tutorials, and of course OpenHelix has tutorials on many of the ones mentioned (those with linked “T”s after the name). Still, this one analysis took a large number of tools and familiarization.

The paper does have a pretty good figure (figure 1) outlining the analysis process. For example, they SIFTed the genome to find gene-associated, non-synonymous, rare and novel and disease associated variations and then analyzed those using dbSNP, HGMD, OMIM and PubMed to analyze something like HFE2 which might have an association with Haemochromotosis. One of my quibbles with the paper, as often is with these papers, is that there isn’t a good methods ‘walk-through’ of the paper using something like Galaxy or Taverna in a history or workflow that would help reproduce the analysis.

We also have a tutorial I’d like to point you to, one that walks through a similar process and teaches users the basics of walking through that process. You can find this tutorial here, it’s free and publicly available. The tutorial walks the user through the analysis of a gene variation, in this case in the CYPC9 that effects an individual’s response to Warfarin. There is a similar variation (different gene, affects same drug response) in the paper. The tutorial uses the NIEHS SNPs site to get an overview of the variation including SIFT and PolyPhen predictions, then to the UCSC Genome Browser to find an overview of the region, walks through the dbSNP information and does a quick tag SNP analysis using GVS. That tutorial is only one very small step in what will have to be a immense education into genomics and genomics resources.

That is all to point out that the paper is an fascinating first step, and as a first step suggests the gaping holes we will have in bringing personal genomics to medicine.

Ashley, E., Butte, A., Wheeler, M., Chen, R., Klein, T., Dewey, F., Dudley, J., Ormond, K., Pavlovic, A., & Morgan, A. (2010). Clinical assessment incorporating a personal genome The Lancet, 375 (9725), 1525-1535 DOI: 10.1016/S0140-6736(10)60452-7