On BioScience and Life and Such

Posts Tagged ‘diagnostics’

Nothing is ever absolutely negative

In Uncategorized on October 31, 2009 at 1:19 pm

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Homer Simpson exclaiming the famous quote
Image via Wikipedia

On a late Friday afternoon

Quality control department:  “You missed the last two samples in this dilutions series”.

Me:  “Yeah, that’s kind of why we use dilution series – to find our detection limit”.

Quality control department: “But, even though very diluted, those two samples were positives. That means this was an error and needs an error-report”.

Me: “Well no, we define a limit where we can be 99,99% certain that we can reproduce a positive result, these dilutions will be well below that limit”.

Quality control department: “But, that means that you can newer be 100% sure of a negative answer”.

Me: “That’s correct, although the concept you are touching upon (the lack of absolute negation/negativity) is valid for any test and consequently, of a philosophical nature”.

Quality control department: “Then we can never give out a negative answer, at least not without saying that there’s a chance it may be positive after all”.

Me: in silence “¤%%”&&¤…doh” and out loud “”Would that be wise ?”.

Quality control department: “We believe so !!”.

Please notice the use of the word “believe”.

So there you go, hit in the face by the same arguments that created the vaccine-autism wars, the ID vs. natural evolution discussion, the religion meets atheism quarrel……..you cannot prove the absence of something, ergo – it must be there. The mother of all fallacies, but impossible to scientifically refute.

I’ll keep trying though.

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Flip a coin Diagnostics ? Worse ? Better ?

In Uncategorized on February 25, 2009 at 3:40 pm

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A good easy to do , quick test for colorectal cancer is something diagnostic labs have been wanting (and trying to make) for many years. Now, DNA-direct has introduced a new genetic test. The test is based on methylation of the vimentin gene.

As a learning excercise for myself (and my lab), I’m going to run through the numbers to try to assess whether this is a good test or not and consequently whether we should look into something similar (like this commercial test-kit).

The Bayesian method of assessment is very general and can be used for any diagnostic test where the following is known:

  1. Disease incidence – Colorectal cancer in US approx 50 / 100 000 = 0,05 % (numbers from National Cancer Institute).
  2. Test specificity (true negatives) – approx 86 % (from DNA-direct web site).
  3. Test sensitivity (true positives) – approx 75 % (from DNA-direct web site).

Now what we want to do is calculate the Bayesian probability of actually having cancer when you have a positive test result (procedure from here). Summary of calculations as follows: i) 75 % of 50 true cancer patients test positive = 37,5, ii) 100-86 = 14 % of 99950 true healthy patients test positive = 13993. Bayesian probability i/ii = 0,27 %.

The test may be cost-effective as a general population screening test since a positive test means your chances of having colon cancer at the time of testing has increased from 1/2000 to 6/2000. In addition, if you choose the right age group (aged over 50), screening using this test may be a good thing. Decisions on population screening however, are made  by health officials on a national level and not by individual labs.

Representing an individual lab and seeing that the chances of you having cancer when you receive a positive test result using this test is, – believe it or not -, o,3 %, which means that out of a thousand people tested only 3 of them will be diagnosed correctly, – the only possible conclusion must be:

Worse than a coin flip, – Not a test I would use in my laboratory.

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By this certificate I am certifiably decision-certified

In Uncategorized on December 9, 2008 at 11:40 am

Christmas came early this year. Thank you Andrew of ThinkGene:

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After whole genome sequencing comes PCR

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


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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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