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Thanks for your response! So is it true to say every genome could be sequenced, assuming time and money isn’t an issue?

by exdsq 5y ago

timy2shoes 5y ago
Starting material is a huge problem. You need at least 50ng of DNA for an Illumina sequencing run, usually more if you want to sequence ultra deep, which you will need for whole genome sequencing. For PCR you need at least 0.1ng (usually higher) of DNA. But a single cell has about 80 pg of DNA. So you need to amplify the DNA several orders of magnitude before you can apply standard PCR. Several approaches can solve this problem, DOP-PCR, MDA, MALBAC. But each results in biased amplification, with differing biases with each method. Source: I worked on the computational modeling of this problem in grad school, https://academic.oup.com/bioinformatics/article/30/22/3159/2391301 https://academic.oup.com/bioinformatics/article/30/22/3159/2...
- tux1968 5y ago
  The most interesting idea from the article, that was new to me, was using larger samples available from each parent, to augment and guide the analysis of the small amount of material available from the embryo. Obvious idea after you hear it, but very clever nonetheless.
dekhn 5y ago
if you're asking whether we could sequence 7 billion people, yes, it would be absolutely possible. Obtaining samples would be harder than the sequencing. If you really took this seriously there would be only 3 sequencing sites in the world and they would be located close to the largest datacenters. Each sequence is about 100G data (the raw data file that's shipped around) so if you really wanted to keep all of that it's 700 exabytes, but since you're sequencing everybody, you can instead create a tree structure of deltas from references with additional nodes representing major haplotypes and other structure. This would be more like ~1M-1G/person, so 7 petabytes to 7 exabytes, well within the storage limits of a modern datacenter cluster. To go along with that storage, you'd also need ~1M fast CPUs and ~250K fast GPUs, plenty of RAM, and a really good privacy and security story. All of that could be formatted for large-scale analytics and the problem treated much like machine learning/data science problems in ads and other similar areas. If you're really serious, this is just a bulk buy for one of the data center providers and they would be happy to make a fixed profit margin contract to do this for you. I helped set up all the infrastructure to enable google to do this ~10 years ago (I got a patent on compressing DNA for storage) and now they're at the point of hosting this sort of service (terra bio). I could do everything I described above for $25B but there is absolutely no medical reason to do anything of this scale.

Thanks for your response! So is it true to say every genome could be sequenced, assuming time and money isn’t an issue?

by exdsq 5y ago

Thanks for your response! So is it true to say every genome could be sequenced, assuming time and money isn’t an issue?

Starting material is a huge problem. You need at least 50ng of DNA for an Illumina sequencing run, usually more if you want to sequence ultra deep, which you will need for whole genome sequencing. For PCR you need at least 0.1ng (usually higher) of DNA. But a single cell has about 80 pg of DNA. So you need to amplify the DNA several orders of magnitude before you can apply standard PCR. Several approaches can solve this problem, DOP-PCR, MDA, MALBAC. But each results in biased amplification, with differing biases with each method. Source: I worked on the computational modeling of this problem in grad school, https://academic.oup.com/bioinformatics/article/30/22/3159/2391301 https://academic.oup.com/bioinformatics/article/30/22/3159/2...

tux1968 5y ago
The most interesting idea from the article, that was new to me, was using larger samples available from each parent, to augment and guide the analysis of the small amount of material available from the embryo. Obvious idea after you hear it, but very clever nonetheless.

dekhn 5y ago

if you're asking whether we could sequence 7 billion people, yes, it would be absolutely possible. Obtaining samples would be harder than the sequencing. If you really took this seriously there would be only 3 sequencing sites in the world and they would be located close to the largest datacenters. Each sequence is about 100G data (the raw data file that's shipped around) so if you really wanted to keep all of that it's 700 exabytes, but since you're sequencing everybody, you can instead create a tree structure of deltas from references with additional nodes representing major haplotypes and other structure. This would be more like ~1M-1G/person, so 7 petabytes to 7 exabytes, well within the storage limits of a modern datacenter cluster. To go along with that storage, you'd also need ~1M fast CPUs and ~250K fast GPUs, plenty of RAM, and a really good privacy and security story. All of that could be formatted for large-scale analytics and the problem treated much like machine learning/data science problems in ads and other similar areas. If you're really serious, this is just a bulk buy for one of the data center providers and they would be happy to make a fixed profit margin contract to do this for you. I helped set up all the infrastructure to enable google to do this ~10 years ago (I got a patent on compressing DNA for storage) and now they're at the point of hosting this sort of service (terra bio). I could do everything I described above for $25B but there is absolutely no medical reason to do anything of this scale.