37 replies to this topic

[albedo]

Ymc, I tried to have a look at that particular SNP (rs121911886) but found nothing. Is it spelled rightly?

[mag1]

Could anyone give an opinion on how low the cost for whole human genome sequencing might go using nanopore technology?

Is the only marginal cost the electricity?

 

With current sequencing technology there is a whole bunch of costly messy chemistry, yet nanopores appear to have removed this 

from the process.

 

Are we truly on the verge of a $100 or $10 genome?

[Danail Bulgaria]

As I understand it, the cost should be at the cost of the standart blood tests, thaken in medical labolatories.

 

Only because the cost of the device itself and for the human, that makes the test, if you want it to be proffessional.

 

I imagine it something like taking a blood sample to count your white blood cells.

 

[ymc]

[quote name="albedo" post="765596" timestamp="1457512331"]

Ymc, I tried to have a look at that particular SNP (rs121911886) but found nothing. Is it spelled rightly?[/quotes

Oops. It is rs121918116

[ymc]

Could anyone give an opinion on how low the cost for whole human genome sequencing might go using nanopore technology?
Is the only marginal cost the electricity?

With current sequencing technology there is a whole bunch of costly messy chemistry, yet nanopores appear to have removed this
from the process.

Are we truly on the verge of a $100 or $10 genome?

Currently, the accurarcy of nanopore sequencing is only about 78-82% for each 2D read. Cost is about US$4,000/GB for 2D reads. For 30x genome, this costs US$360,000. Therefore it is still significantly more expensive than Illumina's US$1,500. Not to mention much lower accuracy requires even higher coverage.

But all this can change if the nanopore CTO can make good on the promises he made recently.

[mag1]

I have no idea what 1D and 2D means!

The term flowcell is also unclear.

 

On the below url Oxford is claiming their new R9 pores have 1D accuracy of 75-80%.

They also refer to outputs of 6 terabases/day on their Promethion sequencer

which only costs about $75,000 versus $10 million for a HiseqX.

 

The $20 flowcells sound quite nice, I guess though we are really not yet at $20/Gb.

(An $1800 nanopore genome would already be competitive.) Yet, for a technology that

is still on an improvement curve $400,0000 per genome seems quite impressive.

 

Also unsure about the sequencing workflow that would be used with nanopores.

With the current technology using 100 bp reads, perhaps the 30X coverage is to

an extent related to finding the right place to put each segment. Yet, with nanopore 

technology which might allow for real time assembly one might have the flexibility 

to use different coverages in different parts of the genome. For example,

if one had a 1000 bp segment from an exome, one might want to read it

100 times, and double check any suspicious SNPs by reversing the DNA and

sequencing it again.

 

If 1D means that you can simply throw in DNA and the nanopore would sequence base pairs

without the need for complex chemistry with these flowcells, then you would be moving

to a marginal cost for a genome equal to the cost of electricity. Free genome sequencing?

It would not be possible for current genomics technology to ever move to a zero marginal cost genome.

 

Can't wait for the $100 nanopore genome!

 

http://omicsomics.bl...dy-got-one.html

[ymc]

I have no idea what 1D and 2D means!

The term flowcell is also unclear.

 

On the below url Oxford is claiming their new R9 pores have 1D accuracy of 75-80%.

They also refer to outputs of 6 terabases/day on their Promethion sequencer

which only costs about $75,000 versus $10 million for a HiseqX.

 

The $20 flowcells sound quite nice, I guess though we are really not yet at $20/Gb.

(An $1800 nanopore genome would already be competitive.) Yet, for a technology that

is still on an improvement curve $400,0000 per genome seems quite impressive.

 

Also unsure about the sequencing workflow that would be used with nanopores.

With the current technology using 100 bp reads, perhaps the 30X coverage is to

an extent related to finding the right place to put each segment. Yet, with nanopore 

technology which might allow for real time assembly one might have the flexibility 

to use different coverages in different parts of the genome. For example,

if one had a 1000 bp segment from an exome, one might want to read it

100 times, and double check any suspicious SNPs by reversing the DNA and

sequencing it again.

 

If 1D means that you can simply throw in DNA and the nanopore would sequence base pairs

without the need for complex chemistry with these flowcells, then you would be moving

to a marginal cost for a genome equal to the cost of electricity. Free genome sequencing?

It would not be possible for current genomics technology to ever move to a zero marginal cost genome.

 

Can't wait for the $100 nanopore genome!

 

http://omicsomics.bl...dy-got-one.html

 

Well, they have yet delivered the Promethion sequencer and also R9 chemistry. So at this point, it is still all about hype.

 

They hyped their Minion sequencer two years earlier than they actually delivered it. Also, the Minion sequencer has been around for two years already but it is still not fully commercialized yet. So their claim for the pricing is not yet real.

 

Having said all that, I am a fan of their Minion sequencer. It will be great for this field if they can deliver what they promise.

[albedo]

Good to see more research confirming the significance of FOXO3A gene.

Ultimately, to get the most out of againg genomics, functional analysis on the most common haplotypes (ie combo of mutations on one chromosome) of APOE and FOXO3A genes should be studied. But I suppose the funding is not there

Typically, functional analysis of drug metabolism genes are conducted. Possibly due to the drug companies and the resource and $$$ to do that.

 

Again looked at FOXO3 and pop into this more recent (2018) study non yet posted in this thread, going along your previous lines wrt uncommon homozygote genotype:

 

Bae H, Gurinovich A, Malovini A, et al. Effects of FOXO3 Polymorphisms on Survival to Extreme Longevity in Four Centenarian Studies. J Gerontol A Biol Sci Med Sci. 2018;73(11):1439-1447.

https://doi.org/10.1093/gerona/glx124
 

"Previous studies note specific FOXO3 single-nucleotide polymorphisms (SNPs) associated with human longevity. However, it is not clear if these SNPs influence mortality risk beyond the oldest 1 percentile of survival. Using data from four longevity studies (total n = 8,266, age range 96-119 years for cases), we tested gene-wide association between 107 SNPs and survival to at least the oldest 1 percentile of survival for the 1900 birth cohort (≥96, white males; ≥100 white females). This analysis replicated 17 previously published variants, several of which are significant expression quantitative trait loci of FOXO3; rs6911407 and rs2253310 have the most significant effect on FOXO3 expressions in brain tissue. We then performed a survival analysis to determine if any of these 107 SNPs impact upon mortality risk beyond the oldest 1 percentile. While none of the 17 published variants was significantly associated with mortality risk beyond this extreme age, an uncommon homozygote genotype of rs9384680 exhibited the strongest association with mortality risk (p = 2.68E-04) in only 11 females, a heretofore unreported association. These analyses replicate the previous association of common variants of FOXO3 with older age but these common variants do not modify risk for mortality at ages beyond the oldest 1 percentile age of survival." (bold mine)