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Is there a large dataset of anonymized DNA samples that we could try this tool against? Does 23andme do something like that? I hope they don't but it would be v

Is there a large dataset of anonymized DNA samples that we could try this tool against? Does 23andme do something like that? I hope they don't but it would be very useful for just this one case!

TechnicalVault 9y ago
23andMe use a genotyping array so they probably don't type STRs only SNPs
AlexCoventry 9y ago
Amazingly, it looks like they still use Sanger sequencing, and a lot of the uncertainty will probably come from genotyping errors. There is a lot of anonymized genotype data in the 1000 Genomes Project (http://www.internationalgenome.org/data http://www.internationalgenome.org/data), but the devil is really in the genotyping details with this kind of thing. It looks like in the validation project (https://www.documentcloud.org/documents/4113877-1-19-17-Exhibit-I-FST-Executive-Summary.html https://www.documentcloud.org/documents/4113877-1-19-17-Exhi...), they went from biological samples to sequence data to analysis results, which is the right approach. With this kind of low-througput genotyping so much depends on the accuracy of the genotyping method, though, which in turn depends on the lab, the protocol, the technicians, and sometimes even the weather. The software is not where I would start, in worrying about forensic evidence based on this method, though it definitely could be a source of errors.
- dekhn 9y ago
  I'm not sure what you mean by "amazingly, it looks like they still use Sanger sequencing". Sanger is considered gold standard-- all HTS genome methods are validated against it.
  - AlexCoventry 9y ago
    For this task, the low throughput harms performance. There are genotyping methods which will measure tens of thousands of common variants for a couple of bucks. And the more genotypes you have, the surer you can be of a match, even given a slightly higher genotyping error rate.
    - dekhn 9y ago
      I think you may be misunderstanding my point (it's not clear if you are an expert in this area; I have more than a passing knowledge of DNA). In every area I have worked in, Sanger sequencing is considered gold standard and is used whenver the results are being used for medical purposes. That includes genotyping as well as verifying the results of WGS> It's considered a critical QC step. Throughput doesn't matter if you have false-positive or false negative errors that cause erroneous medical decisions.
      - AlexCoventry 9y ago
        I'm very familiar with Sanger sequencing. Base for base it's one of the most accurate methods. It is by no means worthy of being considered a gold standard, it's just somewhat better. And the drawback is that dollar for dollar, it's pretty inefficient. You can genotype all the common variants using an Affymetrix gene chip,and base your inference on vastly more data. For forensic analysis, where the goal is to discriminate genomes, that would be much more accurate. Maybe go back and verify the most discriminatory/confirmatory loci with Sanger sequencing after that.

Is there a large dataset of anonymized DNA samples that we could try this tool against? Does 23andme do something like that? I hope they don't but it would be very useful for just this one case!

TechnicalVault 9y ago

23andMe use a genotyping array so they probably don't type STRs only SNPs

AlexCoventry 9y ago

Amazingly, it looks like they still use Sanger sequencing, and a lot of the uncertainty will probably come from genotyping errors. There is a lot of anonymized genotype data in the 1000 Genomes Project (http://www.internationalgenome.org/data http://www.internationalgenome.org/data), but the devil is really in the genotyping details with this kind of thing. It looks like in the validation project (https://www.documentcloud.org/documents/4113877-1-19-17-Exhibit-I-FST-Executive-Summary.html https://www.documentcloud.org/documents/4113877-1-19-17-Exhi...), they went from biological samples to sequence data to analysis results, which is the right approach. With this kind of low-througput genotyping so much depends on the accuracy of the genotyping method, though, which in turn depends on the lab, the protocol, the technicians, and sometimes even the weather. The software is not where I would start, in worrying about forensic evidence based on this method, though it definitely could be a source of errors.

dekhn 9y ago
I'm not sure what you mean by "amazingly, it looks like they still use Sanger sequencing". Sanger is considered gold standard-- all HTS genome methods are validated against it.
- AlexCoventry 9y ago
  For this task, the low throughput harms performance. There are genotyping methods which will measure tens of thousands of common variants for a couple of bucks. And the more genotypes you have, the surer you can be of a match, even given a slightly higher genotyping error rate.
  - dekhn 9y ago
    I think you may be misunderstanding my point (it's not clear if you are an expert in this area; I have more than a passing knowledge of DNA). In every area I have worked in, Sanger sequencing is considered gold standard and is used whenver the results are being used for medical purposes. That includes genotyping as well as verifying the results of WGS> It's considered a critical QC step. Throughput doesn't matter if you have false-positive or false negative errors that cause erroneous medical decisions.
    - AlexCoventry 9y ago
      I'm very familiar with Sanger sequencing. Base for base it's one of the most accurate methods. It is by no means worthy of being considered a gold standard, it's just somewhat better. And the drawback is that dollar for dollar, it's pretty inefficient. You can genotype all the common variants using an Affymetrix gene chip,and base your inference on vastly more data. For forensic analysis, where the goal is to discriminate genomes, that would be much more accurate. Maybe go back and verify the most discriminatory/confirmatory loci with Sanger sequencing after that.