Additional Analysis of AncestryDNA Data

NOTE: Getting Advice About Genetic Testing

I have a friend that asked me what extra information she could get from her raw AncestryDNA data.  I've studied by own 23andMe data extensively, so I thought it would be useful to show what tools can also be applied to raw data from other genetic testing services.

I have not purchased an AncestryDNA kit for myself, so all the analysis that I performed was for somebody else.  Therefore, I will not mention any specific results from this analysis.

First, you may find it useful to convert your raw data to 23andMe format.  You can use this Perl script (AncestryDNA_to_23andMe.pl) to convert your file.  The Perl script can be run using instructions similar to those provided here.

Here are some potentially useful tools to learn more from your AncestryDNA data:

1) Interpretome - free, but requires 23andMe format file
2) Custom scripts - free, but requires 23andMe format file (and probably some comfort with programming)
3) Promethease - can directly use raw AncestryDNA file, but it costs $5.  I would probably recommend trying to use the free options first.

At first, I wasn't certain how well these strategies would work.  For example, I thought AncestryDNA might focus on non-functional regions that wouldn't affect disease risk.  However, I think there is a decent amount of additional information that can be gained from the raw data.

For example, all the functions that I tested in Interpretome worked properly.  Additionally, I found 2,581 AncestryDNA SNPs were listed in the GWAS Catalog.  Of those 2,581 SNPs, 1,337 were risk allele the individual that I tested.  This is less than I had for my 23andMe data (3,050 with GWAS Catalog annoations, 1,626 risk alleles within GWAS Catalog variants), but I think it is decent for an assay that don't provide any health reports to the user.

For those that are interested, here is a venn diagram of the overlapping 23andMe variants (V3 23andMe chip, AncestryDNA result from a few months ago):

You can see that the 23andMe chip covers ~50% more of the genome, but the AncestryDNA chip still covers a fair number of nucleotides.  My only real problem is the lack of labeling data from X, Y, and MT chromosomes as such in the raw data.  There are chromosomes listed as "23" and "25," so I initially guessed that "24" is the Y-chromosome.  However, I noticed that randomly selected rsIDs from chromosomes "23" and "25" both came from the X-chromosome.  So, I don't see a simple way to change those into a standard format.

Nevertheless, I think the information from chromosomes 1-22 provide a lot of information to review.  I hope this post helps AncestryDNA customers find something interesting!

Review of Biopunk

Biopunk is a book discussing biological research that isn't conducted in traditional research setting (like an academic lab or a pharmaceutical company).  The book covers a wide variety of topics such as a philosophical discussion about what motivates good scientists, how legal and political decisions affect scientific progress, and recent developments in the field of "DIY bio" (where the book mostly focuses on personalized medicine and synthetic biology).  Throughout the book, Wohlsen also provides several cool factoids, like the Bridges of Cherrapunji that are engineered from living tree roots.

One chapter focuses on DTC genetic testing, where Wohlesen provides both an overview of this industry as well as accounts of individuals who have utilized DTC testing.  For example, Raymond McCauley conducted his own DIY bio research on metabolites in his own blood in order to try and better understand his 23andMe result indicating an increased risk for macular degeneration.  Although Wohlesen acknowledges "McCauley did not hesitate to concede that the results do not show anything conclusive," I think this is a very cool example of how DIY Bio can help inquisitive scientists try to learn more about themselves outside a formal research setting.

My subsequent research on Raymond McCauley also led me to learn more about DIYgenomics.org, which provides tools to help users further analyze their 23andMe data for health risk, drug response, and athletic performance for individual SNPs.  In some ways, this reminded me of the new, free Interpretome tool, but Interpretome can load my 23andMe data more quickly and with a more streamlined interface.  Nevertheless, I think it's good to know that this option is out there.

There were also a few aspects of the book that disappointed me.  For example, many accounts of biopunk research seem to focus more on buying used lab equipment off craigslist or eBay than new technological developments that can help democratize research.  It also seemed like a lot of the "biopunks" were pretty well-educated and not necessarily good examples of what I would consider amateur scientific research.  Also, I was somewhat disappointed at how difficult it was to additional information on some of the start-ups / organizations that were mentioned in the book (which has only been out for a few months).

For example, the chapter "Cancer Kitchen" discusses how John Schloendorn and Eri Gentry studied the role that the immune system played in cancer using Schloendorn's own cancer cells, which led the creation of DIY nonprofit called Livly to develop cancer immunotherapies (and Gentry later co-founded BioCurious, another DIY nonprofit).  However, the Livly website described in the book is no longer hosted on the internet (the old url, provided on the Livly facebook page, now links to an unrelated website).  Likewise, BioCurious only seems to have a facebook page with limited information.  Even with limited funding, the company can at least create a free Google Sites website (like my personal website) in order to more effectively convey information about the company.

I was also very interested in learning more about the Pink Army Cooperative (a DIY drug company attempting to deliver personalized treatments for breast cancer).  This time, I was able to find a generally well-designed and informative website, but I couldn't find much information about concrete research accomplishments (to be fair though, Wohlsen does warn readers that "so far, Pink Army is more a concept than an actual co-op").

Although it was frustrating that I couldn't learn much more about these specific non-profits, Biopunk has successfully encouraged me to learn more about the DIY bio movement.  Who knows, maybe I'll even stop by a meeting for my  local DIYbio chapter!

Democratizing Scientific Research

Today, I came across a very interesting blog post by Christina Agapakis (via a GenomeWeb article). This post focuses on efforts to "democratize scientific research.” For the most part, the article discusses a post on another blog and the efforts by a group called DIYbio, which stands for “do-it-yourself biology.” She also emphasizes the need to make formal changes in the way institutions conduct scientific research, and I particularly liked some of her suggestions for improvement:

"What if there were more opportunities for high-paying technical jobs in science for people without advanced degrees? What if there were more biotech vocational programs to learn the skills you would need to work in these jobs? What if it were easier and cheaper for groups of scientists and engineers everywhere to turn ideas and hypotheses into technology and knowledge? What if there were real ways for knowledge to become power for that kid living in South Central LA?"

In regard to the issues brought up directly in her post, I think Christina is a little too harsh on DIYbio. I do agree that the organization's efforts are probably not sufficient to help intelligent individuals “[living] in a community plagued by violence and poverty” reach their full potential, and it is probably reasonable to assume that most of the participants are “white, middle class, and primarily male.” However, I think DIYbio positively contributes to the production of new ideas and products that would not otherwise be feasible. To be fair, Christina does say that DIYbio has helped promote “scientific participation and enthusiasm” and could be a useful model for developing programs for underprivileged individuals, but her opinions about DIYbio are mostly negative. She also claims that DIYbio perpetuates “the myth of the Victorian Gentleman Scientist,” who “[pursues] a 'pure' science not because of an interest in money and free of any state control but because of a deep curiosity with the power of the natural world.” I certainly agree that the Gentleman Scientist is an undesirable model for scientists that is unlikely to produce practical research and does not provide a reasonable venue for research for anyone without prior financial security. However, I honestly didn’t get that vibe from reading over the DIYbio website, although I should admit that my knowledge is limited because I hadn't heard of DIYbio before today.

In general, I am a big supporter of anything that removes politics from scientific research because I think personal and professional bias compromises the objective judgment that is so critical to good science. I think this requires fair assessment of scientific progress that emphasizes the impact of a specific result (and the effectiveness of the methods to achieve that result) and limits the role of authority as much as possible. For example, I think it would help if the peer-review process for scientific journals was a double blind process. Currently, the reviewers know the author names and institutional affiliations, but the authors do not usually know the identity of their reviewers. I know some exceptions to the latter case but not the former case (please correct my ignorance if you know of some examples). Of course, this would not be a perfect solution. Some reviewers may be able to recognize the work done by established scientists due to biological systems and methods employed in previous publications, and well-connected scientists will probably be friends with some reviewers and can give them a heads up that they have submitted an article for peer review. This is slightly tangential to the topic of DIYbio, but my ideas are relevant to the broad concept of "democratizing” scientific research by formal changes in institutional policies.

There is also a very interesting (and long) response to Christina’s post that does a good job discussing how “[it] is entirely possible to develop high level expertise outside of the formal system” and also noting that certain avenues of research (like “programming and electronics’) are much more feasible for the everyday scientist than research in biology or chemistry. Materials for biological research can be harder to acquire and more prone to regulation. For certain types of biological research, such as biomedical research, it is also relatively difficult to bring therapeutics to the market without a formal research position, in part due to the need to run clinical trails and gain FDA approval. The author of the comment specifically mentions over-regulation. I agree that some regulation is definitely unnecessary and hinders scientific progress (for example, I personally think the FDA should only limit the use of drugs due to toxicity without also considering effectiveness, and instead allow physicians to decide on the own if the treatment is effective and superior to alternative methods), but I do think that there is some rationale for not allowing everyone access to stuff like anthrax.

In short, I think informal biology research is a good thing that can benefit society (as acknowledged in Christina’s concluding paragraph), and I also think it would also benefit society to employ formal institutional changes to encourage individuals from varied backgrounds to conduct scientific research.