Home > Uncategorized > How far is whole genome sequencing from the clinics

How far is whole genome sequencing from the clinics

A few weeks ago, I cam across a comment by an FDA official regarding the clinical utility of next generation whole genome sequencing. According to the official, current sequencing technologies need to improve its accuracy by a few orders of magnitude before they’re any useful in the clinics. Really?

I have a different opinion. The FDA’s view is well known to be, for a good reason, very conservative. For a full genome with 6G bases, with Complete Genomics’ technology, you can already achieve a precision where there’re only some ~3000 – 10000 errors. Is this good enough? It depends.

Take the post-natal diagnostic market for example. Majority of the hereditary diseases that cytogeneticists are trying to diagnose have copy number changes (gains and losses) rather than point mutations, and they’re big events: >10kb in almost all cases. For traditional methods (let’s not go back to “ancient” times where karyotyping is used) say SNP arrays, this presents a challenge, but not so much for sequencing. In fact, whole genome sequencing is already being evaluated in the post-natal space. Knowingly, in a space where the reimbursement level is only ~$1500, next-gen sequencing at the current price point is not viable. Therefore, here what’s preventing NGS to enter the clinical labs is the cost, not the current precision level.

The cancer market? It’s kind of a mixed bag at the moment. NGS, even at the current precision level, provides a whole slew of useful information that can help with diagnosis, prognosis and therapeutic decisions, but it also presents challenges. Aside from the cost (which is more tolerated in cancer), the vastly unknown nature of cancer and the boat load of information that NGS generates do not lead to an easy solution. There’s also a general lack of pharmacogenomics links with mutations vs drugs to use. Admittedly, we have a long way to go there.

Here the focus has been on whole genome NGS. If we move to targeted sequencing, there are far more applications one can use it for (not necessarily market size wise: cancer is still the single biggest one out there!), and many are indeed being commercialized (check out companies like Sequenom, Aria Dx and Verinata etc.).

Categories: Uncategorized
  1. Yuker Wang
    January 26, 2012 at 17:57

    Your error rate for Complete Genomics doesn’t match the number in this paper.
    Hugo Y K Lam et al
    performance comparison of whole genome seq platforms
    Nature Biotech, Jan 2012


    • January 26, 2012 at 21:22

      Hi Yuker,

      You’re right: it doesn’t match. Aside from my minor reservation about this otherwise very solid paper, we do have a Science paper in 2010 where the error rate was reported as 1 in 100k bases, which translates into 60k in 6G base reads. We’ve advanced beyond that in the last 2 years and are well with in the range I said. What’s confusing is often how these error rates are calculated and reported. Not being a bioinformatics guru myself, I don’t intend to try confusing you any further except to say that all of the current next gen data analysis methods (including the Complete pipeline) have a huge amount of data massaging, and can lead to distinctly different results.


  2. February 11, 2012 at 23:24

    Ok, I had to admit that these numbers are really deceptive sometimes… I’ve come back to corroborate my numbers, and it turns out that the estimates are a bit too optimistic. In the 2010 Science paper, it was essentially a false positive rate, which is different from error rate because there are false negatives where point mutations are not detected for example. Also there are still no new publication to prove our improvement beyond the 2010 paper so it might not be all that convincing to just say “we’ve improved beyond that”. A more conservative estimate may be around 10k – 30k errors. By and large though, it doesn’t change what I intend to speculate đŸ™‚

  1. No trackbacks yet.

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out /  Change )

Google+ photo

You are commenting using your Google+ account. Log Out /  Change )

Twitter picture

You are commenting using your Twitter account. Log Out /  Change )

Facebook photo

You are commenting using your Facebook account. Log Out /  Change )


Connecting to %s

%d bloggers like this: