A great post on a subject that has huge potential to impact UK genomic-medicine positively. I’d agree with Vincent’s sentiments about positivity though. It is too easy to point to the potential problems and lack of details with the current plan, although those very clearly need pointing out. Stuart makes the very valid point that the announcement seemed to come out of nowhere with little substance.

I’d say we may need 50x coverage for somatic analysis which is the norm in ICGC.

Genomes will always be more expensive than exomes, and exome will be more expensive than targeted sequencing. Without limitless sequencing capacity turnaround time always has to be considered and this is one of three major issues I see for the NHS (clinical benefit, cost, turnaround). Personally I favour targeted approaches as I believe they are more digestible by users (from my research-sequencing experience).
TSB have pushed into targeted sequencing as Stuart points out and that project should be reviewed as part of the evidence for investment at the level the government has suggested. There is already a large effort within the NHS to sequence many 1000′s of exomes so the clinicians are well aware of the paradigm that is rapidly becoming established in the USA.

But I do think the government is right to focus the discussion on genomes, it makes good headlines and is easier to explain to the public as almost everyone has heard of the Human Genome Project. As long as the details of the project are focussed on getting the most benefit for patients and the NHS then the announcement can surely be welcomed.
The biggest problem I see is that this is not new money. £100M is a reasonably large investment but not as big as it could have been and it comes from somewhere else in the NHS. Why not pump £1B into genomic-medicine, this would be small beer compared to the Bank bailout, would stimulate highly-skilled job creation and drive genomic medicine into almost every area we need it in.

Currently there is no facility in the UK that could process 100,000 Human genomes at £1000 each, using today’s HiSeq 2000 at 4 lanes per genome; for 30-50x coverage you would need to run one instrument every day until the year 2700! Assuming the UK will complete this in 10 years we’d need around 70 HiSeq 2000s, which co-incidentally is not far off current UK capacity. However buying that many new instruments would gobble up almost half the budget. It turns out we need £500 genomes instead!

I don’t see Oxford Nanopore Technologies brining out a viable product that this project can start using for at least another two years, probably longer.

Lastly, there is a real risk that under EU tendering laws this project could be run outside the UK or potentially in China. That would see almost all the jobs move out of the UK and would be a bad news story. Far better to build new infrastructure here in the UK and not ins the South-East where staff and space are expensive.

PS: Will I see you on the steering committee meeting next month?

This being said I am quite a bit more positive about this announcement than you are. I do not know exactly what the NHS invests per patient to diagnose a rare genetic disorder, but I think this is quite high currently. If this initiative can start shifting this business to more modern sequencing technologies this would be a valuable outcome.

Whole genome may still be a waste today but whole exome is probably not. And there may not be any substantial difference in price between sequencing an exome or a targeted approach for a few 100s of genes. Lastly, data analysis can, should and will be largely automated, especially if one discards most of the data and only considers a subset of reliable genes that are generally free of false positive (because the sequence is unique and clean enough).I think this analytical cost will soon become relatively small.

So in my opinion, especially if this money is spent on people who would already receive some sort of genetic testing, the cost may be much lower than expected, and eventually generate savings. We’ll have to sort the analytical and data storage issues at some point anyway, and now is as good a time as any. So we might as well get started. Plenty of initiatives like this one will start all over the US I suspect, so the timing is probably right.