Biogazelle offers mRNA sequencing on plasma – interview with CSO prof. Jo Vandesompele

on March 6, 2017

Jo, congratulations with this amazing achievement of your R&D team at Biogazelle. Tell us, why are you so excited about the work you have done?

What we offer today is a truly novel application. mRNA sequencing in fluids has not been offered to date by any other sequencing service provider. Also, there is hardly any literature on comprehensive characterization of extracellular mRNAs, for example in the context of a biomarker discovery program. At best, some rely on quantitative or digital PCR to measure specific mRNAs in fluids [see selected scientific reading, below]. Almost everybody is focusing on microRNAs in their biomarkers screens in liquid biopsies: there are thousands of publications annually on miRNAs in fluids but hardly any studies on mRNA.

I believe the main reason for this is that the methods to measure long RNA molecules in degraded low input RNA samples were not ready. That is why we have now brought together expertise from two fields: extracellular RNA from liquid biopsies and the technology to measure mRNA in a sensitive and reproducible manner in fluids. We are truly pioneering the field of mRNA sequencing enabled liquid biopsy screening.

What have you done to set op this application?

We developed the workflow together with Illumina in a research collaboration focusing on RNA in body fluids. We started developing this method two years ago, measuring various different types of blood-derived body fluids. Today, we are ready to offer a sequencing workflow that specifically measures mRNA expression in a small volume of plasma [only 0.2 ml]. This workflow is both reproducible and sensitive: typically, 6000 to 8000 genes are detected.

To further leverage the power of mRNA, in parallel, our dry lab R&D team developed an RNA sequencing variant analysis pipeline. This proprietary pipeline builds upon our expertise in scalable data processing and variant analysis, and allows the detection of single nucleotide variants, small insertions and deletions, and fusion genes in circulating RNA. This puts us at the forefront of three attractive and innovative domains: liquid biopsies, mRNA as extracellular RNA marker and RNA sequence variant analysis.

With this development you offer new means to researchers. What is the added value of this new method in comparison to what you could offer before today?

mRNA sequencing on plasma opens up an entire new world for our customers! Since at least 10 times more mRNA genes are detected in plasma than microRNAs, this new application provides an order of magnitude more potential to find relevant disease or treatment response biomarkers. Furthermore, as the specific functions of mRNAs are generally better understood than non-coding RNAs, it is more straightforward to interpret the resulting mRNA patterns and biomarkers.

This method fits perfectly in your offer of RNA biomarker development using plasma. Is the workflow ready for clinical studies?

From a technical perspective and after 2 years of development, the method is ready to study plasma mRNA. For other body fluids, we recommend to first do a pilot study to assess technical feasibility. From a biological point of view, however, many questions remain as the tools to answer these were missing, until today. What we do know now is that plasma in general gives better results than serum in terms of sensitivity and reproducibility, and that the mRNA detection rate varies depending on the type of plasma. Therefore, we would encourage our customers to ensure standardized sample collection procedures when embarking on an RNA biomarker development adventure.

 

While there is a lot that we still do not know or understand from a biological perspective, the study of extracellular RNA is a booming field and having access to robust workflows for the sensitive detection of circulating mRNA will enable us to address the questions. Without a doubt, mRNA sequencing on plasma is extremely promising. If you would like to discuss your project needs, sign up for free scientific support from our experts.

 

Are you interested in hearing more about our new and unique offer? Reach out to Jo at any of these upcoming events where he will talk about mRNA sequencing on plasma and how this application may accelerate your research:

  • Illumina’s France & Benelux User Group Meeting (March 13-14, Marseille, France). Jo will present our workflow on the second conference day at 10:30 AM. View the entire program.
  • Revolutionizing next-generation sequencing (March 20-21, Antwerp, Belgium). Watch out for Jo's talk on day 2 at 3:10 PM. Take a look at the program.
  • 8th international Gene Quantification Event (April 3-7, Freising, Germany). Jo will give a key note lecture on Monday April 3rd at 2 PM. Check out the conference agenda.

 

Selected scientific reading — mRNA biomarkers in plasma

  • Chan et al. (2013). The potential clinical utility of serial plasma albumin mRNA monitoring for the post-liver transplantation management. Clinical Biochemistry, 46(15), 1313–1319.
  • Chen et al. (2000). Telomerase RNA as a Detection Marker in the Serum of Breast Cancer Patients. Clinical Cancer Research, 6(10), 3823–3826.
  • Koha et al. (2014). Noninvasive in vivo monitoring of tissue-specific global gene expression in humans. PNAS, 111(20), 7361–7366.
  • Shen et al. (2012). Thymidylate synthase mRNA levels in plasma and tumor as potential predictive biomarkers for raltitrexed sensitivity in gastric cancer. International Journal of Cancer, 131(6), E938–45.
  • Shen et al. (2014). Plasma mRNA expression levels of BRCA1 and TS as potential predictive biomarkers for chemotherapy in gastric cancer. Journal of Translational Medicine, 12(1), 355.
  • Silva et al. (2001). Detection of Epithelial Messenger RNA in the Plasma of Breast Cancer Patients Is Associated with Poor Prognosis Tumor Characteristics. Clinical Cancer Research, 7(9), 2821–2825.
  • Pun et al. (2014). Plasma Bmi1 mRNA as a potential prognostic biomarker for distant metastasis in colorectal cancer patients. Molecular and Clinical Oncology, 2(5), 817–820.
  • Zhang et al. (2015). Direct Serum Assay for Cell-Free Bmi-1 mRNA and Its Potential Diagnostic and Prognostic Value for Colorectal Cancer. Clinical Cancer Research, 21(5), 1225–1233.
  • Zhou et al. (2016). Plasma LUNX mRNA, a non-invasive specific biomarker for diagnosis and prognostic prediction of non-small cell lung cancer. American Journal of Cancer Research, 6(2), 452–458.