Letters to the Editor

Date of reader’s letter: February 2, 2011

Subject: Affymetrix – Preanalytix – gets ignored

I enjoyed reading your analysis of Affymetrix – it complimented other research I was doing on Affymetrix.

Isn’t the Qiagen-BDX partnership reliant on Affymetrix technology? I may have read too much into my analysis of the Qiagen/BD partnership.

But, if you look at Qiagen year end financial reports for 2009 – you see that Preanlytix is a Revenue rocket ship – although small, the Revenue number is climbing fast. If Affymetrix technology is a key ingredient in the Preanalytix story – it would seem that BD or Qiagen are potential acquires of AFFX.

I am not an insider or even remotely connected to the Bio tech world – I am merely an individual investor who got curious about AFFX getting downgraded and started doing some digging.

Just curious on your thoughts on PreAnalytix and whether AFFX technology is key to the Revenue.

Best Regard.

A Reader (name withheld at reader’s request)

Date of response: February 15, 2011

Dear Reader,

Thank you for your question regarding Affymetrix and the PreAnalytiX product.

In response to your question, I don’t believe that Affymetrix is the key ingredient in the PreAnalytiX’s product success. The key ingredient is PreAnalytiX’s ability to store mRNA without losing its biological signature, as well as new strategies the company can deliver to solve problems that limit their technology for accomplishing this task.

Specifically, PreAnalytiX’s value is based on its ability to maintain RNA integrity in peripheral blood samples that are collected routinely in clinical practice.

Wright and his colleagues describe the nature of this challenge:

“Although peripheral blood samples are collected routinely in clinical practice, maintaining RNA integrity in such samples and stabilizing their biological signatures have proved difficult. A widely used method for obtaining total RNA from leukocytes requires isolating peripheral blood mononuclear cells (PBMC) by density -gradient centrifugation, which requires both instrumentation beyond what is available in the typical clinical setting and manipulations of 1-2 hours that may cause interfering signatures (5) (Wright et al. 2008)…

To reduce the occurrences of such signature changes, investigators have introduced technologies that decrease the time between blood draw and RNA stabilization Two products available for this are PAXgene (PreAnalytiX) and Tempus (Applied Biosystems) (ibid).

You might want to evaluate companies that produce new mRNA stabilization technology and not Affymetrix’s microarray value in this equation, unless Affymetrix has made changes in its sequencing platform acquisition activities since the DNAScribe article was written. According to Asmann and his colleagues, “…, microarray technology suffers from well-known limitations including insufficient sensitivity for quantifying lower abundant transcripts, narrow dynamic range and non-specific hybridizations. Additionally, microarrays are limited to only measuring known/ annotated transcripts and often suffer from inaccurate annotations [6]” (Asmann et al. 2009).

At the same time, Affymetrix’s expertise in reagents, based on its 2008 acquisition of USB Corporation, may enable it to solve some of the problems that occur during mRNA stabilization.

Here’s one problem described by Wright and his colleagues:

“Although these systems may stabilize RNA at the point of collection, scientists have found that they introduce interfering signatures because of the abundance and variability in the amounts of alpha- and beta -globin mRNA, which can obscure signatures of biological interest (Wright et al. 2008).

Affymetrix’s approach to solving one problem is described in an article by Liu and her colleagues:

“Gene expression profile studies of human blood samples in the context of epidemiological surveillance of immunological signatures are confronted by numerous challenges. Previously, we found that increases in hemoglobin from whole blood PAXgene samples of healthy and ill patients contributes to decreased sensitivity of detection of transcripts on Affymetrix microarrays,(1) and others have shown that spiking increasing amounts of globin mRNA into total RNA from cell lines results in decreasing detection of transcripts (Affymetrix technical note: Globin Reduction Protocol: A Method for Processing Whole Blood RNA Samples for Improved Array Results. Santa Clara, CA). To curtail this problem, two methods for globin mRNA reduction have been commercially developed. The method from Affymetrix uses the specific binding of peptide nucleic acid (PNA) oligos to the 3′ end of globin mRNA to inhibit reverse transcription during cDNA synthesis (.2) The method from Ambion, removes globin mRNA from total RNA via hybridization with biotinylated DNA oligos that specifically capture globin mRNA followed by binding with streptavidin magnetic beads. Both methods seem to offer particular pros and cons depending on the intended application (Liu et al. 2006).

For example, Ambion’s method would not work well in populations with a diversity of diseases and phenotypes: ”These results have significant impact on population level protocols. For instance, in populations with a diversity of diseases and phenotypes, one may not obtain uniformly high-quality RNA even using the PAXgene tubes; thus, the capture oligo method would not be compatible “ (ibid).

While comparing mRNA blood stabilization products, you should look at Applied Biosystems and its Tempus product. While doing so, you will also look at Life Technologies Corporation (Applied Biosystem’s parent company) and evaluate its in-house stable of companies that have DNA Sequencing Platforms and compare these to Affymetrix’s microarrays.

Again, thank you for reading DNAScribe and for taking the time to e-mail your question.

With best regards,


Elizabeth M. Rogers
PO Box 645
Greenwich, CT 06836

  1. Asmann, Y. W., E. W. Klee, E. A. hompson, E. A. Perez, S. Middha, A. Oberg, T. M. Therneau, D. I. Smith, G. A. Poland, E. Wieben & J.-P. A. Kocher (2009) 3 tag digital gene expression profiling of human brain and universal reference RNA using Illumina Genome Analyzer. BMC Genomics, 10.

  2. Liu, J., E. Walter, D. Stenger & D. Thach (2006) Effects of Globin mRNA Reduction Methods on Gene Expression Profiles from Whole Blood. Journal of Moleular diagnostics, 8, 551-558.

  3. Wright, C., D. Bergstrom, H. Dai, M. Marton, M. Morris, G. Tokiwa, Y. Wang & T. Fare (2008) Characterization of Globin RNA Interference in Gene Expression Profiling of Whole-Blood Samples. Molecular diagnostics and Genetics, 54, 396-405.