SNPedia: a wiki supporting personal genome annotation, interpretation and analysis
Michael Cariaso; Greg Lennon
Nucleic Acids Research 2011; doi: 10.1093/nar/gkr798
Friday, December 9, 2011
Friday, November 18, 2011
Using Promethease
Last year 23andMe introduced a pricing model with a one year minimum subscription. I think it's a great service and will continue to pay my monthly fee to continue participating in the online discussions and get their updated analysis, but I'm sure a few people will decide updated genetic information is not in their budget this year. This post will show you how to keep getting new information about your genome for many years to come, with zero further expense.
To do this, you will need to download your raw data while your account is still in good standing. To begin, visit https://www.23andme.com/you/download/
After logging in, you will be presented with security questions such as these
.
After a few moments your download will begin and you will receive a file named similar to genome_John_Smith_Full_201112034567.zip. Remember where you save it, once your subscription runs out you won't be able to get it again!
Now visit http://www.snpedia.com/index.php/Promethease and download the latest version from the bottom of the page.
Run Promethease.
Here you can see the Windows and Mac versions side by side.
Click Next to move to the Genotype Files page.
Click on the Load button and then find your genome_John_Smith_Full_201112034567.zip file from the beginning of this walk-through.
Then click Open to select your file. The filename will appear in the box.
Press Next to validate your file and move to the next screen. Along the way it will show how many genotypes are in your file. The number is probably just a bit below 1 million.
The next screen asks you to choose your Ethnicity. For many of us there is no perfect match, and that's fine. It has only a minor effect on the report that will be produced. This just shows some reference values for comparison to highlight how rare or common your genotypes are. Pick whatever seems closest and don't worry if it is rather distant from your true origins.
There are several more screens to go. You can just click Next on all of them until you get to the last one.
Output Folder -- On this screen you choose where to store your completed analysis. You are specifying both the directory for all of the supporting files as well as the name for the top level report. The default values are based on your usual 'My Documents' folder and the name of your genotype file from the earlier step.
Optional -- This screen allows registered commercial users of Promethease to identify themselves after their initial email to info@promethease.com . But if you're just running Promethease for youself or familiy members and not charging you should just leave it blank and click Next.
Payment -- Click this button to pay $2 and unlock extra features such as running much faster or predicting the genetics of your children based on your partner's genotype file. That also introduces extra screens which are fairly self explanatory, but not further discussed in this blog post.
Promethease Wizard -- The last screen before the system begins your analysis. Just click Next to begin.
Status -- Promethease has begun your analysis and will contact the central server to figure out what SNPedia knows about your genotypes. This will need approximately 4 hours to run.
After approximately 4 hours you will see text similar to the above. It should have launched your web browser and showed you the report which looks similar to this one. In the report click on '...show more...' to drill deep into everything SNPedia knows about your data. Click on hyperlinks to be taken into SNPedia to see the full text, and find links to primary sources. As you learn more about your genome we hope you'll make edits to SNPedia and help teach all of us more. It's a big genome and we can't understand it without your help. We hope what we've learned so far is helpful to you. Rerun your report every few months to watch our growth and improved understanding.
To do this, you will need to download your raw data while your account is still in good standing. To begin, visit https://www.23andme.com/you/download/
After logging in, you will be presented with security questions such as these
.After a few moments your download will begin and you will receive a file named similar to genome_John_Smith_Full_201112034567.zip. Remember where you save it, once your subscription runs out you won't be able to get it again!
Now visit http://www.snpedia.com/index.php/Promethease and download the latest version from the bottom of the page.
Run Promethease.
Here you can see the Windows and Mac versions side by side.
Click Next to move to the Genotype Files page.
Click on the Load button and then find your genome_John_Smith_Full_201112034567.zip file from the beginning of this walk-through.
Then click Open to select your file. The filename will appear in the box.
Press Next to validate your file and move to the next screen. Along the way it will show how many genotypes are in your file. The number is probably just a bit below 1 million.
The next screen asks you to choose your Ethnicity. For many of us there is no perfect match, and that's fine. It has only a minor effect on the report that will be produced. This just shows some reference values for comparison to highlight how rare or common your genotypes are. Pick whatever seems closest and don't worry if it is rather distant from your true origins.
There are several more screens to go. You can just click Next on all of them until you get to the last one.
Output Folder -- On this screen you choose where to store your completed analysis. You are specifying both the directory for all of the supporting files as well as the name for the top level report. The default values are based on your usual 'My Documents' folder and the name of your genotype file from the earlier step. Optional -- This screen allows registered commercial users of Promethease to identify themselves after their initial email to info@promethease.com . But if you're just running Promethease for youself or familiy members and not charging you should just leave it blank and click Next. Payment -- Click this button to pay $2 and unlock extra features such as running much faster or predicting the genetics of your children based on your partner's genotype file. That also introduces extra screens which are fairly self explanatory, but not further discussed in this blog post. Promethease Wizard -- The last screen before the system begins your analysis. Just click Next to begin. Status -- Promethease has begun your analysis and will contact the central server to figure out what SNPedia knows about your genotypes. This will need approximately 4 hours to run.After approximately 4 hours you will see text similar to the above. It should have launched your web browser and showed you the report which looks similar to this one. In the report click on '...show more...' to drill deep into everything SNPedia knows about your data. Click on hyperlinks to be taken into SNPedia to see the full text, and find links to primary sources. As you learn more about your genome we hope you'll make edits to SNPedia and help teach all of us more. It's a big genome and we can't understand it without your help. We hope what we've learned so far is helpful to you. Rerun your report every few months to watch our growth and improved understanding.
Sunday, July 17, 2011
0.1.116 - It's a Family Affair
Russell: I just ran the newly released Promethease 0.1.116, it's getting better and better. It has me nailed pretty well.
me: I notice your report isn't clear on your ancestry and we now do a better job of that for some reports so in time I'd like to see what I can do to polish up that side of your data. SNPedia has you and your mother publicly, but since you have so many family members privately, take a look at these images from another family which shows where the chromosomes agree between family members. promethease_corpas_family_comparison_newfamily.html
me: Looking at you and your mother genome_Russell_Letkeman_20081023161035_newfamily.html I notice a region of similarity on chromosome 2 with a run of
similarity, and a little red spot on chromosome 11 where you and your mother are quite distinct.
me: I notice your report isn't clear on your ancestry and we now do a better job of that for some reports so in time I'd like to see what I can do to polish up that side of your data. SNPedia has you and your mother publicly, but since you have so many family members privately, take a look at these images from another family which shows where the chromosomes agree between family members. promethease_corpas_family_comparison_newfamily.html
me: Looking at you and your mother genome_Russell_Letkeman_20081023161035_newfamily.html I notice a region of similarity on chromosome 2 with a run of
similarity, and a little red spot on chromosome 11 where you and your mother are quite distinct.
Thursday, May 26, 2011
ESHG2011
Today was the end of the Galaxy 2011 conference and on Saturday, May 28 the European Society of Human Genetics (ESHG) will begin in Amsterdam. Ramunas of http://cancergenetics.wordpress.com and I would like to invite other netizens for a meetup. Bloggers, wiki editors, and lurkers are invited to
join us
Sunday, August 8, 2010
Party like it's 0.1.99
Promethease 0.1.99 is out and there is a new video tour of it's features. The most important is an interactive x-y scatter plot which you will see at the end.
If you have more questions see Promethease/Features
If you have more questions see Promethease/Features
Monday, January 4, 2010
SNPedia's Top 10 SNPs of the Year
SNPedia now contains nearly 10,000 SNPs and to welcome 2010 we'd like to highlight at least 10. These SNPs have been selected based on an elusive and ultimately subjective combination of medical importance, statistical believability, and overall general interest. This isn't objective science though, so feel free to comment about why your favorite SNPs should have made the list.
1. rs4244285: The antiplatelet drug clopidogrel (Plavix) is the #2 selling drug in the world. This SNP in the CYP2C19 gene can tell you if it's unlikely to be doing you much good; carriers of 1 or especially 2 A alleles don't benefit much in terms of lowered heart attack incidence based on several studies published over the last year. And actually, this fairly common SNP affects how you metabolize plenty of other drugs as well, including anti-depressants and anti-ulcer drugs.
2. rs4149056: Speaking of bestselling (>100 million prescriptions/year) drugs, one of the adverse effects associated with statin use is the possibility of myopathy (muscle problems including weakness, cramping or pain). Carriers of 1 or 2 C alleles for this SNP in the SLCO1B1 gene taking statins are at ~5 or 17 fold higher risk, respectively, for statin-triggered myopathy. Ouch.
3. rs1799853, rs1057910 & rs8050894: How about one more - actually three more - affecting a widely prescribed drug? When assessed together, these SNPs in the CYP2C9 & VKORC1 genes help predict something that's otherwise both tricky and overly empirical to determine: the optimal dose of the anticoagulant drug warfarin (Coumadin ), used primarily to help prevent thrombosis and embolism in patients with high blood pressure. The FDA now recommends - but doesn't require - testing warfarin patients for these SNPs. Here's a long-standing wish, good for 2010 and most likely beyond: Medicare announces it will reimburse for testing these SNPs, given that over 1 million Medicare beneficiaries take warfarin each year.
4. rs10757278: The region of chromosome 9p21 with this SNP (and it's neighbor, rs1333049) has been shown in 2009 by several large studies to indicate at least somewhat increased (~1.3 or 1.7x) risk for coronary artery disease and it's consequences (like heart attacks). But has it added anything to what a cardiologist would already have known based on traditional risk factors like hypertension and family history? Actually, yes - you can classify a patient's risk better when you add the status of this SNP to all the other factors you've already assessed.
5. rs1537415: Sure, lots of SNPs are of interest to MDs, but here's one for DDS's. Over half of us carry at least one allele of this SNP and are therefore at increased risk for periodontitis - so keep flossing!
6. rs3892097: This SNP encodes the CYP2D6*4 allele, the most common nonfunctional variant for this gene. While it can therefore affect the metabolism of about 25% of all known drugs, it's on our list this year due to increasing evidence for poorer outcome among breast cancer patients treated with tamoxifen, the gold standard drug for roughly the last 30 years. Women are typically treated with tamoxifen for 5 or more years, but evidence is mounting that less functional CYP2D6 alleles lead to less endoxifen, which is the active form formed via CYP2D6 metabolism of tamoxifen. Less of the active form means a poorer outcome, so now the question is becoming, can higher doses of tamoxifen overcome this, or should alternative drugs replace it as the gold standard?
7. rs1447295: And now here's one for the guys: this SNP has turned up in studies totaling tens of thousands of patients across multiple ethnic groups as connected to an increased risk for prostate cancer, the second deadliest cancer among men. Although on it's own the increased risk isn't that high (perhaps a doubling of risk even for those carrying two copies), there are now over 20 more SNPs that can be used together to help classify risk. We can hope that more aggressive screening of those deemed to be at higher genetic risk will help decrease prostate cancer deaths.
8. gs138, gs139, gs140: These three genosets (hence the 'gs' prefix) represent the rapid, intermediate, and slow metabolizers amongst you for the detoxifying enzyme NAT2. Debuting in 2009, the algorithms described in SNPedia using seven NAT2 SNPs allow the Promethease software to classify your NAT2 status and thus estimate just how fast you'll clear various toxins (or that hangover?) out of your system. Looking into the 2010 crystal ball: we foresee the use of lots more genosets to predict phenotypes (and ancestry) based on combinations of SNPs.
9. rs17646946 & rs11803731: Two SNPs, both on chromosome 1, yet 27 million bases apart; one is part of the trichohyalin gene, the other abuts a trichohyalin-like gene. One found by a genome-wide association scan by academic researchers, the other by a company harnessing the power of the internet , DNA chips, and customer interest in correlating their DNA with common traits - in this case, hair curliness. We applaud the use of people-power to help prove (and disprove) DNA associations, and in 2009 we began having SNPedia/Promethease users self-report their own associations for a variety of SNPS, regardless of which company they got their genome data from.
10. rs2395029: This SNP just keeps getting more associations every year! As the SNP predicting the presence of an HLA-B*5701 allele, it's been previously associated with a variety of conditions (like psoriasis, or as the FDA agreed last year, abacavir hypersensitivity). This year, it demands attention for the remarkable increase in risk (45 to 80 fold) for liver damage among patients taking the antibiotic flucloxacillin (aka floxacillin). While this SNP is quite rare, it's a good example of a more "deterministic" type of SNP that we can carry.
On that last note, the intersection of less expensive full genomic sequence with greater coverage of rare variations bodes well for all. Think well of all the researchers who make this possible - we thank you for your hard work, we encourage you to choose open access publications, and we look forward to all of your contributions in the coming year!
1. rs4244285: The antiplatelet drug clopidogrel (Plavix) is the #2 selling drug in the world. This SNP in the CYP2C19 gene can tell you if it's unlikely to be doing you much good; carriers of 1 or especially 2 A alleles don't benefit much in terms of lowered heart attack incidence based on several studies published over the last year. And actually, this fairly common SNP affects how you metabolize plenty of other drugs as well, including anti-depressants and anti-ulcer drugs.
2. rs4149056: Speaking of bestselling (>100 million prescriptions/year) drugs, one of the adverse effects associated with statin use is the possibility of myopathy (muscle problems including weakness, cramping or pain). Carriers of 1 or 2 C alleles for this SNP in the SLCO1B1 gene taking statins are at ~5 or 17 fold higher risk, respectively, for statin-triggered myopathy. Ouch.
3. rs1799853, rs1057910 & rs8050894: How about one more - actually three more - affecting a widely prescribed drug? When assessed together, these SNPs in the CYP2C9 & VKORC1 genes help predict something that's otherwise both tricky and overly empirical to determine: the optimal dose of the anticoagulant drug warfarin (Coumadin ), used primarily to help prevent thrombosis and embolism in patients with high blood pressure. The FDA now recommends - but doesn't require - testing warfarin patients for these SNPs. Here's a long-standing wish, good for 2010 and most likely beyond: Medicare announces it will reimburse for testing these SNPs, given that over 1 million Medicare beneficiaries take warfarin each year.
4. rs10757278: The region of chromosome 9p21 with this SNP (and it's neighbor, rs1333049) has been shown in 2009 by several large studies to indicate at least somewhat increased (~1.3 or 1.7x) risk for coronary artery disease and it's consequences (like heart attacks). But has it added anything to what a cardiologist would already have known based on traditional risk factors like hypertension and family history? Actually, yes - you can classify a patient's risk better when you add the status of this SNP to all the other factors you've already assessed.
5. rs1537415: Sure, lots of SNPs are of interest to MDs, but here's one for DDS's. Over half of us carry at least one allele of this SNP and are therefore at increased risk for periodontitis - so keep flossing!
6. rs3892097: This SNP encodes the CYP2D6*4 allele, the most common nonfunctional variant for this gene. While it can therefore affect the metabolism of about 25% of all known drugs, it's on our list this year due to increasing evidence for poorer outcome among breast cancer patients treated with tamoxifen, the gold standard drug for roughly the last 30 years. Women are typically treated with tamoxifen for 5 or more years, but evidence is mounting that less functional CYP2D6 alleles lead to less endoxifen, which is the active form formed via CYP2D6 metabolism of tamoxifen. Less of the active form means a poorer outcome, so now the question is becoming, can higher doses of tamoxifen overcome this, or should alternative drugs replace it as the gold standard?
7. rs1447295: And now here's one for the guys: this SNP has turned up in studies totaling tens of thousands of patients across multiple ethnic groups as connected to an increased risk for prostate cancer, the second deadliest cancer among men. Although on it's own the increased risk isn't that high (perhaps a doubling of risk even for those carrying two copies), there are now over 20 more SNPs that can be used together to help classify risk. We can hope that more aggressive screening of those deemed to be at higher genetic risk will help decrease prostate cancer deaths.
8. gs138, gs139, gs140: These three genosets (hence the 'gs' prefix) represent the rapid, intermediate, and slow metabolizers amongst you for the detoxifying enzyme NAT2. Debuting in 2009, the algorithms described in SNPedia using seven NAT2 SNPs allow the Promethease software to classify your NAT2 status and thus estimate just how fast you'll clear various toxins (or that hangover?) out of your system. Looking into the 2010 crystal ball: we foresee the use of lots more genosets to predict phenotypes (and ancestry) based on combinations of SNPs.
9. rs17646946 & rs11803731: Two SNPs, both on chromosome 1, yet 27 million bases apart; one is part of the trichohyalin gene, the other abuts a trichohyalin-like gene. One found by a genome-wide association scan by academic researchers, the other by a company harnessing the power of the internet , DNA chips, and customer interest in correlating their DNA with common traits - in this case, hair curliness. We applaud the use of people-power to help prove (and disprove) DNA associations, and in 2009 we began having SNPedia/Promethease users self-report their own associations for a variety of SNPS, regardless of which company they got their genome data from.
10. rs2395029: This SNP just keeps getting more associations every year! As the SNP predicting the presence of an HLA-B*5701 allele, it's been previously associated with a variety of conditions (like psoriasis, or as the FDA agreed last year, abacavir hypersensitivity). This year, it demands attention for the remarkable increase in risk (45 to 80 fold) for liver damage among patients taking the antibiotic flucloxacillin (aka floxacillin). While this SNP is quite rare, it's a good example of a more "deterministic" type of SNP that we can carry.
On that last note, the intersection of less expensive full genomic sequence with greater coverage of rare variations bodes well for all. Think well of all the researchers who make this possible - we thank you for your hard work, we encourage you to choose open access publications, and we look forward to all of your contributions in the coming year!
Tuesday, November 24, 2009
Interpreting a Promethease report
This new video helps to explain what is inside a Promethease report.
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