On BioScience and Life and Such

After whole genome sequencing comes PCR

In Uncategorized on October 23, 2008 at 8:56 am

post to news.thinkgene.com

I attended an Applied Biosystems SOLiD seminar the other day. Let me tell you this: the SOLiD system packs some serious sequencing power (as does it’s competitors like Illumina, -and possibly others). Only imagination sets limits to the potential uses for such whole genome (and whole transcriptome !) sequencing. Thus, I found myself continuously drifting off, dream-designing new projects we could set up. But, at the same time I couldn’t keep from thinking that in terms of diagnostics, this a massive overkill. Too much information is not always a good thing when it comes to disease and disease predisposition. If one particular genetic variation is relevant to the symptoms presented, then there’s hardly necessary to return the whole genome or transcriptome. You would end up giving the patient information on a whole range of diseases, – the patient may not want/need to know this. Especially since we know that (currently) there is considerable uncertainty surrounding the future disease-risk associated with most genetic markers. Besides, once you know the relevant genetic regions it would probably be sufficient to run a couple of million markers to determine any predisposition.

Early model of a Polymerase Chain Reaction mac...

Good (?, and really) old PCR.

Image via Wikipedia

Thus, all of these projects ended with good old PCR, which is kind of strange since sequencing one would think, is the superior of the two technologies. Here’s how I figured my (would be) whole genome sequencing projects would go:

  1. Pick species/subspecies/individual trait or disease group
  2. Sequence everything you can get your hands on
  3. Characterize genetic differences be it SNPs, indels, repeats, CNV or any other
  4. And then, …..design PCR/real-time PCR assays for diagnostics/further research and such.

Because, obviously, once everything is sequenced, there’s no need to keep sequencing. My prediction is that at that point (real-time) PCR (and quite possibly Sanger sequencing capillary electrophoresis) will regain it’s lost status as preferred tools for molecular biologists.

So, as a comfort to all those who are unable to jump on the whole genome sequencing train: Not to worry ! We’re just going through a phase. This too shall pass.

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  1. It depends on the economy of what’s necessary. If PCR and sequencing machines cost about the same someday, then there’s little reason to purchase a PCR machine.

    My suspicion is that sequencing will be something performed at sequencing centers to which one mails biological samples and purchases some fraction and accuracy of results as a service —much like computing resources today are purchased. PCR and similar technology will be more like the 1990’s desktop workstation of genomic testing —you have one because it’s not that expensive to own one and because it’s convenient, even though it doesn’t scale, it’s not powerful enough to do everything you want, and may not even be the most economical way to process small tests.

  2. Yes, it’s about the cost, but it’s also about analysis-time. And PCR will only become obsolete when sequencing achieves the same cost, the same time to finished test result and the same precision of diagnostic information. That may happen of course, but I believe it will take some time, and before this happens PCR and sanger-sequencing will remain the tools of preference. The shortcomings of next gen sequencing (like the poor performance on repeats – makes it unsuitable for STR analysis – human ID) will also contribute in favor of PCR and sanger-sequencing.

  3. I am a CLINICIAN, and thus I am thinking as clinican. I wrote in Nature.com, http://www.the-scientist.com/blog/display/55106/, that genetic studies are, first of all, a great businness. Therefore, I frankly suspect that economics may contribute to hindering scientific advances, clinical in nature, which allow me to statethat gene mutations parallel biological systems dysfunctions, bedside evaluated with a simple stethoscope! (1, 2). Recently, also on BMJ blog has been posted the following message of mine:
    My English is poor, not so perfect and fluent as that of journalists in Spain to attend at Ministerial Conference of Environment and Health in Madrid. However, I am sure you all understand whay I mean. Scientists need publicity, especially for spreading among individuals their own theories, rather than to obtain funding. Unfortunately, paramount theories are not expensive, but are not politically correct. For instance, in the AGE of Genomics at the Zenith, who among journalists is authorized to give information that every gene mutation brings about necessarily alteration, i.e., dysfunction, in related biological system, adding that doctors can nowadays bedside evaluate all tissue functions, so that we can gather since birth precise information not only with the aid of genomics, but also with a simple stethoscope? That’s only as example! Other examples everybody may read in this website (3). Finally, The same observation my you read, for instance, on http://www.nature.com, at URLs http://www.nature.com/news/2008/081006/full/news.2008.1152.html?q=2#last-comment
    Finally, I cannot agree with such as statement “Too much information is not always a good thing when it comes to disease and disease predisposition”. Wrong! I have demonstratedthat Primary Preventio is almost realizable if doctors would decise to learn Quantum Biophysical Semeiotics, treating related INHERITED Real Risks, as I am doing since a decade, with DIET, etimologically speaking, Coniugated-Melatonine, and NIR-LED personalized applications.

    1. Stagnaro Sergio. Mutazioni Genetiche e Disfunzioni dei Sistemi Biologici. http://www.ilpungolo.com, 2008,
    2. Stagnaro Sergio. Gene Mutations May Be Assessed Today By Bedside Evaluating Biological System Dysfunction. Medical News Today, 6 November 2008. http://www.medicalnewstoday.com/youropinions.php?opinionid=34199
    3. Stagnaro Sergio. Middle Ages of today’s Medicine, Overlooking Quantum-Biophysical-Semeiotic Constitutions and Related Inherited Real Risk. http://www.sciphu.com November 4, 2008. http://sciphu.com/2008/11/meadle-ages-of-todays-medicine.html

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