Technology Centre

FIMM Technology Centre develops methods and provides a broad spectrum of biomedical research services to researchers locally, nationally and internationally. FIMM Technology Centre operates six core units with a total of 43 technology experts from diverse educational backgrounds being involved in the operations. Technology Centre offers services in the areas of genomics (sequencing, genotyping, transcriptomics, epigenomics, copy number variation profiling and cell line authentication), high throughput biomedicine (screening of chemical compounds, approved drugs, and siRNA, as well as serum, cell and protein lysate microarrays), metabolomics, digital imaging, bioinformatics, and IT using state-of-the-art technologies.

FIMM Technology Centre operates in close collaboration with the Biocenter Finland infrastructure networks and is strongly involved in the European Research Infrastructure (ESFRI) networks (EATRIS, EU-OPENSCREEN, BBMRI). The Centre was supported by Biocenter Finland as a part of the Genome-wide methods, Translational research (The Drug Discovery and Chemical Biology Consortium DDCB, Biobank), Proteomics and Metabolomics, and Bioinformatics networks, the Academy of Finland (EATRIS) and the Systems Microscopy Network of Excellence project.

Genotyping microarray.

In 2014, we significantly increased our throughput compared to 2013 by completing larger projects, and widening our user base to over 100 research groups from local, national and international universities and research institutes, as well as from a few companies. While High Throughput Biomedicine and Metabolomics units more than doubled their revenue in 2014, novel technology and chemistry, as well as optimized assays in genomics services enabled us to reduce the prices and improve the cost-recovery with reduced revenue.

In addition to high quality and high-throughput laboratory services, the Technology Centre offers expertise in project planning, method development, data handling and analysis. In 2014, our staff members were involved in many collaborative research projects with both national and international research groups and were co-authors of more than 20 scientific publications solely based on these projects. As an example, researchers from the Sanger Institute in collaboration with Dr. Vidya Velagapudi from The Metabolomics Unit identified a novel biological process that regulates the production of new bone cells. This pathway involves vitamin B12 but also taurine, a poorly understood amino acid synthesized in the liver. Read more about the study.

Transition towards NGS based readouts

A clear trend towards Next Generation Sequencing (NGS) based readouts in genomics analyses was obvious in 2014. The demand for classical capillary sequencing services decreased 27%, while amplicon NGS sequencing, a tailored turnkey mutation analysis service, showed a 2.3 fold annual increase. Complete service from PCR optimization to detailed variant/mutation reports was delivered for almost 60 projects covering 266 new custom NGS amplicons and nearly 3,800 samples deeply screened for sequence variation. The capillary sequencing services still delivered over 106,000 sequencing reactions, and provided a gold-standard method for validation of disease causing mutations identified by exome sequencing.

A novel NGS readout was developed for targeted methylation analysis

Several genome-wide methods for analysing DNA methylation are available in Technology Centre, but targeted and customizable analysis of smaller genomic regions in a variable number of samples cost-effectively has remained challenging. To overcome the challenge, we built a customizable and flexible targeted methylation analysis option by combining the best parts of the Sequenom EpiTyper and NGS assay workflows. Custom modified Epityper Amplicons were sequenced on the Illumina MiSeq platform to produce a proof-of-principle dataset, which proved to identify more methylation sites than the primer extension based EpiTyper method. The first user projects utilizing the novel method have just been initiated.

FIMM Technology Centre year 2014 in numbers.

Technology Centre Highlights

A growing demand for Clinical profiling services

One important aim of the Technology Centre is to enable early introduction of state-of-the-art methods to translational research and clinical practice. To reach this goal, we have set up fast-track services for exome, transcriptome and genome sequencing, as well as drug sensitivity and resistance profiling of patient samples. Further development of these services in collaboration with research groups at FIMM and the Hospital District of Helsinki and Uusimaa (HUS) in 2014 allows us today to provide a full profiling service starting from processing a blood or bone marrow sample to reporting validated, clinically significant germline and somatic mutations, and personalised drug sensitivity and resistance profiles of 461 approved and investigational oncology drugs.

In 2014, we produced clinical exome, genome or transcriptome sequence analysis for 280 germline and tumour samples from patients referred from over ten university and central hospitals of Finland with an average turnaround time less than a month. A vast majority of the patients suffered from leukaemia, multiple myeloma and primary immune deficiencies (PID), reflecting the research interests of FIMM groups. Exome sequencing provided a molecular diagnosis for 30% of the 80 PID patients analysed thus far, while a possible candidate mutation requiring further research was identified in 25%. Having a biobanking infrastructure, clinical sequencing service and active research under one roof creates a unique opportunity to conduct high profile personalised medicine research and improve clinical diagnostic capabilities by follow up of patients with novel mutations and disease mechanisms.

Today ex vivo drug sensitivity and resistance testing (DSRT) is performed with primary cancer cells from patients with leukaemia and multiple myeloma, as well as cancer cell lines and the drug sensitivity responses are integrated with molecular profiling such as exome sequencing, transcriptomics and phosphoproteomics. DSRT is run in 384-well plate format using assay plates pre-drugged using acoustic droplet ejection with Labcyte Echo550. The viability and cell death of cells is measured and a profiling report is produced in less than a week. The platform is further developed with additional readouts and increasing the number of drugs. Our Labcyte Access Workstation, with Echo550 and Echo525 integration, allows development and set-up of miniaturized follow-up assays, such as reverse-phase protein array and qPCR, using non-contact acoustic dispensing.

Application of the DSRT platform to acute myeloid leukaemia (AML) patient samples has uncovered taxonomic drug-response subtypes and individualised therapy based on DSRT has resulted in several clinical responses. The DSRT platform enables drug repositioning, provides new combinatorial possibilities and allows for linking drug sensitivities to predictive biomarkers.

Starting a Next GenerationSequencing run.

Technology transfer - HPV diagnostics case example

In collaboration with the Norwegian Cancer Registry and Akershus University Hospital in Norway, a highly sensitive and specific protocol for genotyping human papillomavirus (HPV) was developed at FIMM’s Sequencing Unit and transferred successfully to the Norwegian HPV reference laboratory. The existing diagnostic fluorescent oligonucleotide hybridization based HPV Luminex assay was converted into a NGS amplicon assay. This enables a much higher number of strains to be detected, thus facilitating the diagnostic value of the assay. The method development was done in Helsinki by Pekka Ellonen and Sonja Lagström with the samples provided by the HPV reference laboratory. Training of the personnel and the final transfer of protocol was undertaken in one week when Sonja visited Norway in October 2014.

“Close dialogue between the three collaborating parties secured efficient knowledge transfer and troubleshooting. FIMM's professional and efficient handling of this project allowed for its successful conclusion and continues to inspire future collaborative efforts”, commented Dr. Ole Herman Ambur from Akershus.

Nordic platform for sensitive data

As a part of the Nordic Tryggve-NeIC collaboration, FIMM has been establishing a platform for storage and analysis of sensitive biodata together with the other major players (e.g. SciLifeLab, DTU, University of Oslo, CSC, BILS) in Nordic countries.

Technology Centre