3 ms·

Hi Elad, First off I want to say that I appreciate the drive to work on problems like this. I personally think it's a much better use of money than funding yet

by rfc 10y ago

Hi Elad, First off I want to say that I appreciate the drive to work on problems like this. I personally think it's a much better use of money than funding yet another marketing tool to 'revolutionize push notification blah blah'. I am wondering if you can answer a question (probably naive but curious nonetheless). Why not sequence the full genome on a 30x coverage? Why find just the mutations on these genes rather than across the board? The reason I'm asking is that it feels somewhat limiting to focus on only the currently known relationships of mutations rather than collecting the full data set. There's other initiatives, such as SB Genomics, that are doing very interesting work on the Cancer Cloud by utilizing new graphing techniques in data science to understand large scale pattern interactions, but they typically are utilizing the full data set.

eladgil 10y ago
It is really a matter of cost and utility. My answer is specific to "germline genetics" - i.e. inherited risk of disease, rather then sequencing a tumor sample or microbiome. [Cost] In order to provide clinical results in a CAP/CLIA environment we need to ensure sufficient coverage to call all SNV/indels and all CNVs. This means we need much higher average coverage then 30X. Since your exome is just 1-2% of your genome, and your exome encodes 20,000 to 25,000 genes, this means that 30 genes is <1% of your exome which itself is just <2% of your genome. So the Illumina sequencing costs of 30 genes alone are on the order of a fraction of a percent of the cost of doing whole genome (assuming you are using the same machines and the same coverage). Now, there are some caveats to this, e.g.: -You would use a slower, higher output more expensive machine like an X10 to do a whole genome at scale. -You can save some costs by doing whole genome versus a targeted panel as the pulldown step of the panel adds additional unique costs of its own. -This does not include fixed costs of sample collection, or secondary confirmation, or other costs that increase the price per test. This does not include labor costs, bioinformatics, or other items where sometimes dealing with a whole genome is cheaper per bp of DNA then doing a smaller panel of genes. -I think the "$1000 genome" isn't really here yet. In a few years, the cost of sequencing the whole genome will be a few hundred dollars, at which point I think it makes sense to do the whole thing. [Usefulness] It is important to note, however, that most of the genome is not very actionable right now. At Color our focus is on providing you with information you and your doctor can use, which means most of your genome is not characterized well enough to be clinically useful. At this point, depending on who is doing the estimate, only 30-60% of the 20,000+ genes you have are ascribed to a function, and even then it is often unclear how impactful a mutation in those genes are....
- rfc 10y ago
  Awesome, thanks so much for the response. It's clearer now the behind the scenes on what you're doing so appreciate you sharing. You're effectively providing a much needed and critical clinical tool for making more informed decisions on a patient diagnosis - something desperately needed. I can sympathize with many of the regulatory and cost hurdles, especially for dealing with humans. We're in the purchasing process for a MiSeqDX and starting out specifically only on bacterial and viral sequences with an eventual path towards humans once we accomplish CLIA compliance. Long and costly effort... Agree on the "$1000 genome" comment. Our average prep kit is ~$700 and, like you mentioned, once you factor in time, labor, computing costs, etc. the cost is well into the thousands. I've had 4 relatives pass from various cancers which is what got me interested in the field to begin with. Truly hoping we can make some breakthroughs and it is encouraging to see startups such as yours pushing to make that happen. Best of luck!

by rfc 10y ago

eladgil 10y ago

It is really a matter of cost and utility. My answer is specific to "germline genetics" - i.e. inherited risk of disease, rather then sequencing a tumor sample or microbiome. [Cost] In order to provide clinical results in a CAP/CLIA environment we need to ensure sufficient coverage to call all SNV/indels and all CNVs. This means we need much higher average coverage then 30X. Since your exome is just 1-2% of your genome, and your exome encodes 20,000 to 25,000 genes, this means that 30 genes is <1% of your exome which itself is just <2% of your genome. So the Illumina sequencing costs of 30 genes alone are on the order of a fraction of a percent of the cost of doing whole genome (assuming you are using the same machines and the same coverage). Now, there are some caveats to this, e.g.: -You would use a slower, higher output more expensive machine like an X10 to do a whole genome at scale. -You can save some costs by doing whole genome versus a targeted panel as the pulldown step of the panel adds additional unique costs of its own. -This does not include fixed costs of sample collection, or secondary confirmation, or other costs that increase the price per test. This does not include labor costs, bioinformatics, or other items where sometimes dealing with a whole genome is cheaper per bp of DNA then doing a smaller panel of genes. -I think the "$1000 genome" isn't really here yet. In a few years, the cost of sequencing the whole genome will be a few hundred dollars, at which point I think it makes sense to do the whole thing. [Usefulness] It is important to note, however, that most of the genome is not very actionable right now. At Color our focus is on providing you with information you and your doctor can use, which means most of your genome is not characterized well enough to be clinically useful. At this point, depending on who is doing the estimate, only 30-60% of the 20,000+ genes you have are ascribed to a function, and even then it is often unclear how impactful a mutation in those genes are....

rfc 10y ago
Awesome, thanks so much for the response. It's clearer now the behind the scenes on what you're doing so appreciate you sharing. You're effectively providing a much needed and critical clinical tool for making more informed decisions on a patient diagnosis - something desperately needed. I can sympathize with many of the regulatory and cost hurdles, especially for dealing with humans. We're in the purchasing process for a MiSeqDX and starting out specifically only on bacterial and viral sequences with an eventual path towards humans once we accomplish CLIA compliance. Long and costly effort... Agree on the "$1000 genome" comment. Our average prep kit is ~$700 and, like you mentioned, once you factor in time, labor, computing costs, etc. the cost is well into the thousands. I've had 4 relatives pass from various cancers which is what got me interested in the field to begin with. Truly hoping we can make some breakthroughs and it is encouraging to see startups such as yours pushing to make that happen. Best of luck!