Tag Archives: analysis

Good Lord, People, 23andMe is NOT Dead!

Reposting from my personal genomics blog because I think it is important also for the audience of this blog.


23andMe

Good Lord, people, 23andMe is NOT dead! Or closed, or no longer taking orders, or anything like that. I hear this a lot.

“You know, I always wanted to get my genome tested. I was going to try 23andMe, but then the FDA shut them down. Oh, well, missed my chance. [sigh]”

NO! You did NOT miss your chance. Firstly, 23andMe is not closed for business. They still will take your money and your sample. They still will analyze the sample and give you results. From what I’ve been seeing in the results from folk I’ve been helping to look at their data, 23andMe seems to be running the test exactly the same way they always did, for the same SNPs.

They simply are, at this time, not offering their health reports to new customers. It isn’t the data that has changed – it iw what analysis is shared with the customer. Old fogies like me who got their tests done before the FDA folderol” still have access to our old 23andMe health reports, and they continue to improve them.

I have heard nothing to indicate that 23andMe are not working with the FDA to try to make it possible to release health reports again in the future. Issues around that get complicated and I’m going to save them for a later post. Right now, what if you wanted a test for some genetic health information? Can you do it? How long will you have to wait to find out the answers to your health questions?

You can still do it. It isn’t as easy as it was before, but it can be done. I’ve been spending a lot of time talking people through how to do this, and it is time to write it down. If nothing else, it will save me time. This will be the short short version, and I can answer more detailed questions and describe specifics, maybe give an example or two or three.

FIRST, THE DISCLAIMER

Risk is Not Just Genes

Making sense of genetic information is complicated even for experts, which most of us are not. Of course, part of the irony of looking at genetics for health conditions is that most of the time what causes the condition is not just the genetics, but genes PLUS something else. If you don’t find the genes for something, that doesn’t mean you can’t get it; if you do find the genes for something, it doesn’t mean you will get it. It is hardly ever a case of this=that.

What Does Risk Mean, Anyway?

There is also the challenge of figuring out how important the risk is, and whether or not to do something about it. So, my personal risk of celiac disease is over 4 times normal. Wow! That sounds like a lot, doesn’t it? But 4 times normal for celiac risk is still only 1 in 20 people, because normal is about 1 in a hundred. I know someone with celiac risk 17 times normal, which is 1 in 4 people. That’s getting to be pretty serious! But, while celiac is dangerous, it isn’t one of those conditions that is immediately deadly or painful. And my friend still has a 3 in 4 chance of NOT getting celiac, and that is a lifetime risk.

On the other hand, my risk of venous thromboembolism (VTE) is 1.5 times normal. That doesn’t sound like much does it? It’s higher, but only a little bit. So we don’t really need to worry about it, do we? Well, yes. VTE can kill you on the spot, and it is incredibly painful. And normal is 1 in 10 people for lifetime risk. For me, the risk is closer to 1 in 7.

Given that, according to 23andMe, my genetic risk of celiac is roughly 1/20 and my risk of VTE is 1/7, and adding in the comparative dangers of the two diseases, my docs got all excited about the VTE, and not terribly about the celiac. I hope you understand why now, and also a bit more about why genetic risk is complicated.

On Asking for Help

Last part of the disclaimer.

For both of these, celiac and VTE, 23andMe looks at SOME of the genes and SNPs known to be associated with the condition, but not ALL of them. So whatever 23andMe tells me about risk is only part of the picture. It looks at the most important genes, but is still only part of the picture. That’s why you need experts to put all the pieces together, and get more information to fill in the gaps from the 23andMe test.

Everyone always says, “Ask your doctor,” when it comes to finding something puzzling, confusing, contradictory, or worrisome in your genetic tests. I did, and found that most of my doctors didn’t have the expertise to make more out of it than I did. Some poohpoohed the 23andMe results, others made clinical decisions based on them without verifying with other tests, some asked for more medical tests to expand upon what 23andMe had, and one said, “You know more about this than I do, but I’m going to learn.” Here is a quote from an NEJM article a few months ago about the risks and benefits of trusting direct-to-consumer personal genomic services such as 23andMe.

“Clinicians will be central to helping consumer–patients use genomic information to make health decisions. Any regulatory regime must recognize this reality by doing more than simply adding the tagline on most consumer ads for prescription drugs: “Ask your physician.” That is insufficient guidance unless your physician has ready access to a clinical geneticist or genetic counselor.” Annas GJ, Elias S. 23andMe and the FDA. N Engl J Med 2014; 370:985-988. http://www.nejm.org/doi/full/10.1056/NEJMp1316367

Some of the personal genomics service offer phone-in access to genetic counselors. I tried that, and didn’t get helpful answers there, either. Even worse, one of the answers I got was blatantly wrong. It may have been just the genetic counselor who I happened to be talking with, so don’t judge the whole profession by that one person, but do be prepared to keep looking for info if needed. Where I found the most helpful information was in the 23andMe forums, BUT a lot of the info there was unreliable, and I had to sort out what was helpful and what wasn’t.

So, my recommendation is, absolutely DO ask your doctor, ask a genetic counselor if you can, but that might not be enough. You might need to do more research on your own, or find someone you trust to help you with this.

What Good Is It?

So, what good is it then? It gives you clues. Like a detective, you take the clues and look for more information, or ask for more thorough testing, or raise questions that weren’t being asked or addressed before. Some of the clues will be red herrings. Some of them may lead you to a prized solution. For me, these clues ended up dramatically improving my quality of life, and may have even saved my life.


So, now, the short short version. And PLEASE, if someone more expert than me with genomic data reads this and spots any errors, please say so!

PART ONE

1. Get your 23andMe test done.

Pic of the Day - PGenPGEN, Take 2

2. Log in at the 23andMe web site when you are notified that your results are ready.

23andMe

3. Click: Browse raw data.
23andMe: Getting to your raw data

It should look like this:

23andMe: Browse Raw Data

4. Click: Download raw data.
23andMe: Download Raw Data

5. Complete security procedure (log in again, answer security questions, etc.). It should look like this.

23andMe: Downloading Raw Data

6. Answer the question about what type of data and format you want. NOTE: I always choose ALL DNA, unless you have something else specifically in mind.

23andMe: Downloading ALL Your Raw Data Or ...

7. Find the file (which will be named something like genome_Firstname_Lastname_Full_12345678901234.txt)

PART TWO (A): Easier Way

Genetic Genie

Now you have choices. You can dig into the information the easier way, or the less easy way. Let’s start with the easier way.

1. Select a tool to do what you want with your data. There are LOTS of tools people have built to do useful things with 23andMe data files. One of my favorites is Genetic Genie, because it tells you about the MTHFR gene which has become so important in my life. I also am spending a lot of time with Promethease because it is so complete compared to most other 23andMe analysis tools. Lets start with these.

2. Go to the tool of your choice, such as:

Genetic Genie: http://geneticgenie.org/

Promethease: http://www.snpedia.com/index.php/Promethease

3. Follow the directions at the tool, but this almost always requires you to upload your 23andMe data file. Here are more details about doing this with Genetic Genie.

4. Last come what is always the tricky part — making sense of the information you get. That’s worth several posts, but for starters the main point to remember is that the 23andMe test is a place to start, not a final answer. In Genetic Genie, the code, analysis, and text are written by engaged amateurs, not by doctors or genetic counselors. They worked hard, collaborated with a lot of other people, and did a lot of research, but it isn’t going to say the same things your doctor might.

More Tools

23andMe: Tools for Everyone http://www.23andyou.com/3rdparty
NOTE: When 23andMe took out the health reports, they also edited this page to remove links to tools that provide health data from 23andMe data. So, this is interesting and useful, but not sufficient. You’ll have to look somewhere else for most tools.

23++ Chrome Extension: Get more from your data:
http://23pp.david-web.co.uk/getting-more-from-your-data/

Confessions of a Cryokid: Top 10 things to do with your FTDNA raw data (2011) http://cryokidconfessions.blogspot.com/2011/06/top-10-things-to-do-with-your-ftdna-raw.html

Genetic Genealogist: What Else Can I Do With My DNA Results: http://www.thegeneticgenealogist.com/2013/09/22/what-else-can-i-do-with-my-dna-test-results/

International Society of Genetic Genealogy: Autosomal DNA Tools: http://www.isogg.org/wiki/Autosomal_DNA_tools

Resqua: Q: What should I do after generating my Gene variance report? http://resqua.com/100005927200207/what-should-i-do-after-generating-my-gene-variance-report

Think Exponential: Get SNPd! http://thinkexponential.com/2013/01/10/why-you-should-get-snped/

PART TWO (B): Less Easy Way

Linking Disease Associations with Regulatory Information in the Human Genome

Actually, there are a LOT of different “less easy ways.” You can open the raw data file in a text editor and search manually for specific pieces of information. Or, if you code, you can write a little program to do some of the hard work for you.

Basically, it comes down to doing a lot of research, the hard way, by hand. But, believe it or not, I am doing it. I’ve had a lot of help from people who offered tips or comments in the 23andMe or MTHFR.net forums, on Facebook, on Twitter, and comments on these blogs. I am NOT an expert, but like most readers of this blog, just someone who wants or needs to know more. This is what I’ve learned and figured out on my own, offered as an example, nothing more.

Critical Background

23andMe gives SNP-based data. SNP stands for single nucleotide polymorphism. Polymorphism means something that can be itself but in different ways, our eyes are eyes whether they are blue or brown or hazel or violet or any other natural eye color. I won’t give an introduction to genetics here, but there are several online resources that explain these ideas, with one of the best resources being Genetic Home Reference from the US government. Depending on how much you want to know, you may wish to take the Coursera courses Introduction to Genetics and Evolution (Duke U) or Experimental Genome Science (U Penn).

1. What SNPs do you want to know about? Check here:

RegulomeDB (Stanford): Linking Disease Associations with Regulatory Information in the Human Genome: http://regulomedb.org/GWAS/

I have also found SNPs of interest in research articles, PUBMED, and other places, but this is a good start. The SNP identifier (what you need) will look something like this:

rs2187668

2. Find out which polymorphism is the one considered “healthy” or “normal”, and which one is the one associated with risk of disease? These maybe called “risk alleles” or
simply polymorphisms.

For example, for SNP “rs2187668” (one of the celiac risk SNPs) the risk indicator is (T), while the normal is (C).

3. Open your 23andMe raw data file in a text editor, like WordPad (Windows) or TextEdit or TextWrangler (Macintosh).

4. Search for the SNP you want to know about. The data will be in four columns:
– RSID
– Chromosome
– Position
– Genotype
You need to know about the first and last columns, RSID and Genotype. It will look a little like this.

rsid…..chromosome…..position…..genotype
… [many other rows of data] …
rs2187668…..6………32605884…..CT

So, this person (me) has for that SNP one risk allele “T,” (which I happen to know is from my dad, by comparing it to his scan) and one normal allele “C,” (which must, by default, be from my mom, since for every gene pair we have gotten one from each parent).

5. Repeat for all the other SNPs associated with the condition you are researching.

6. Search for more information and articles about those SNPs, the condition, and more. You can’t make sense of this without more information. And ask lots of questions.

More Tools

ENCODE:
About: http://www.genome.gov/encode/
Data: http://genome.ucsc.edu/encode/

ENSEMBL Genome Browser: http://useast.ensembl.org/

OpenSNP: https://opensnp.org/ OR https://opensnp.org/snps/

SNPedia: http://www.snpedia.com/

UCSC Genome Browser: http://genome.ucsc.edu/

At the Movies: Friends and Neighbors

Pain, awards, traveling autism, morphing metadata, potentially poisoned chocolate, technology use and drug abuse … It doesn’t sound like today’s videos have anything in common, but what they share is that all of them are either by people I know personally or are from places I’ve been and loved.



Empowering People for Community Health in Manistique, Michigan http://www.youtube.com/watch?v=Q-rajjRA9ds

Did you see that Manistique, Michigan is one of the winners of the Robert Woods Johnson Foundation Roadmaps to Health Prize? How awesome is that?! Completely aside from my loving the place, and aside from my mentor Maurita Holland having a long standing relationship collaborating with the tribe mentioned in the video, it’s just a great and inspiring story. I love the line, “Teach kids skills for a lifetime,” in the context of building healthy lives. I’m excited. You can see more videos about RWJF awardees in their grantee playlist. More info about the Manistique project here at the award announcement.



The United States of Autism Official Trailer http://www.youtube.com/watch?v=td1pxNXNjjU

While this isn’t exactly new as a Youtube video (originally uploaded in 2011) it is new in the sense that the movie the trailer was made for is finally actually OUT! The premiere in NYC is set for April. I found out through a Twitter friend of mine (TannersDadTim) who’s been working in support of this project for three years.

The United States of Autism: http://usofautism.com/ Arrange a screening: http://www.tugg.com/titles/the-united-states-of-autism

“Follow one man’s 11,000 mile, 40 day journey across the American landscape to visit twenty families and individuals affected by autism while searching for answers for his own son. With interviews from around the nation that include the widest spectrum of backgrounds – each conducted in the participants’ original language – the film weaves a broad and compelling tapestry across the spectrum of American life in all its faiths, disparities, colors, and cultures. What he learns along the way will change not only his life, but the lives of those he meets, forever. It’s a story about the best days that still lie ahead for our nation, the families, and the people who give America its heart.”



Cataloging Unchained http://www.youtube.com/watch?v=IQRHNdw2_yw

This one is for the librarians and metadata geeks in the crowd, and anyone with a sense of humor. My favorite line? “Metadata is inherently lazy. It just sits there unless you make it work. [sound effect: whip cracking]” Roy Tennant and I have known each other virtually, through email lists (mostly Web4Lib) and Twitter and professional publications, but have never met in person. I am delighted to see the library geeks talking about exploding library systems out into public and collaborative spaces.

“Created by Roy Tennant to introduce his talk “Leveraging WorldCat: Data Mining the Largest Library Database in the World” at the OCLC EMEA Regional Council Meeting 26 February 2013.”



RiskBites: Chocolate, Lead and the Measurement Conundrum http://www.youtube.com/watch?v=lZ6FvTU2rqk

I’m a HUGE fan of RiskBites, partly because I’m a fan of Andrew Maynard, and try to hang out over at his department on campus as much as possible. I have blogged about them here before. They just keep getting more and more interesting, and more and more intricate. This particular one is on such a great topic (chocolate!) and has really rich information resources in the video notes.



[Project] PainTrek – Mobile Pain Tracking and Analysis (Beta – v0.9) http://www.youtube.com/watch?v=CP8tvz2nmpY

I’ll be blogging more about this one later. Earlier this week (last week?) I livetweeted an event where this marvelous app was presented. PainTrek was the brainchild of Dr. Alex DaSilva in the University of Michigan School of Dentistry. I might add I worked in the School of Dentistry for over ten years, and have a deep and abiding love for the place and the people. Hearing Dr. DaSilva present on this and express so clearly his powerful desire to aid migraine patients didn’t do a thing to diminish that.



TEDxDesMoines – Peter Komendowski – Media Literacy: Mind Versus Mindful https://www.youtube.com/watch?v=8FwCUCquFsE

Last but not least, a video from TEDxDesMoines on media literacy. I grew up about a half hour from where this was recorded. The speaker, Peter Komendowski, isn’t someone I know, but he is an activist for Drug Free Iowa and talks here about the ways in which technology can be as addictive as drugs. This seemed especially timely, given that the National Day of Unplugging was just yesterday. Here are a couple of lines I really liked from his talk. “Tightness allows for a lot of efficiencies, but is it really humane?” “Do we really understand the difference between real and virtual?”

#Inaug13 and Much More: Twitter Hashtags & American Politics

Twitter/Gov: Peak Inauguration Moment

For much of the past year, I’ve been tracking hashtags used for the American political process — elections, debates, and now the inauguration. Part of the reason is that I am still trying to persuade various communities (peers, scientists, researchers, clinicians, friends, relatives, etcetera) that social media has both interest, value, utility, and traction. I thought this was a big enough topic to illustrate this dramatically. I’m still finishing data collection, but a great deal of what I’m observing is distilled in this tweet, this quote from Obama’s inauguration speech earlier today.

Let’s just say there was a lot of debate, and a lot of name-calling, and both are quite evident in the tweets I’ve collected. While I’m not at the point of being ready to analyse what I’ve collected, I do have some observations from just looking at all this. Please note, this is all anecdotal, as I haven’t actually run the numbers yet, and some of this may change when I really do.

During the election, I was surprised several times. One surprise was when I noticed that the Democrats and the Republicans (or Obama supporters and Romney supporters) differed in some interesting ways in how they used Twitter. For the official party tweets, the Democrats had more variety of hashtags used than the Republicans. For the unofficial real-folk tweets there was more variety from both, with name-calling and rudeness from both parties, but more of the name-calling from the Romney supporters than from the Obama supporters. The Obama-supporters had more unique tweets, the Romney-supporters did a lot more retweeting of things someone else said.

What surprised me today was that some of this flipped. While there was a lot of tweeting going on from both sides, for today’s activities so far, the Republicans and tea-party Twitter streams shows much greater diversity of hashtags than the Democrats or Obama-supporters, who are using fewer hashtags than they have at any point previously. The name-calling, though? Is even more one-sided, and it’s the same side.

So, let me head back to gathering my data, and then let’s see what I find when I can actually dig into it. More to come! In the meantime, if you have any doubt whatsoever that Twitter has traction, check out these two tweets about the metrics from tweeting during the inauguration.