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Strengthening Clinical Proteomics Capabilities

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The Swedish Research Council has approved approximately SEK 13,6 million for investments in advanced mass spectrometry and in automatization robots at Proteomics Core Facility. Proteome analysis, is a key technology for taking precision medicine to the next level.

“By strengthening these clinical proteomics capabilities, we can add a valuable data layer in precision medicine research, working closely with clinical genomics programs and regional clinical trial units, as well as biobanks” said Carina Sihlbom, unit manager at Proteomics Core Facility.

The grant is a third of the total amount of SEK 41 million, given to the Swedish national infrastructure for biological mass spectrometry BioMS, and shared by local nodes.

Advanced MS and Automated Robots

The investment will be used for a new sophisticated mass spectrometry instrument with ion mobility for data-independent acquisition MS (DIA-MS), as well as parallel reaction monitoring (PRM) MS-assays.

This will provide a great robustness for routine operations, and high throughput of samples and data. Researchers will also be able to use the high sensitivity of the instrument to identify more peptides and posttranslational modifications (PTM).

“Our aim here is to adapt this method to support clinical trials also in prospective sample analysis” Carina Sihlbom said.

The investment also includes automated sample preparation robotics. For researchers, this will mean time efficient sample preparation, as well as standardization of workflows.

“This type of robotics highly increases the number of samples handled per day while reducing the cost per sample.”

Every third or fourth year, similar investments when it comes to technological importance and financial range, have been made at PCF, Carina explains, adding that the Proteomics Core Facility has competent staff with long experience in many different fields of MS. 

“We are already familiar with these techniques and will also get specific training in the new software so that we can continue to give expert support to our users”.

Valuable for Diagnosis and Treatment

When having the new instruments and robotics ready, Carina hopes that this will aid research that leads to better diagnosis and treatments for patients.

“The entire approach on how we diagnose and make treatment decisions is undergoing a paradigm shift in the form of precision medicine. Targeted drugs are tailored for an individual patient based on extensive and informative biomarker data” Carina said.

The precision medicine field is in part technology driven and is now rapidly moving toward including proteome analysis to represent the molecular phenotype. This will result in improved capabilities to select most effective treatment for each patient leading to reduced treatment toxicity, improved outcome and lower drug development costs.

More about the new MS instrument

DIA is a method  for peptide sequencing, in which all ions within a selected mass range are fragmented and analyzed in parallell As comparison, in a data-dependent acquisition (DDA) only a fixed number of precursor ions are selected and analyzed, one at a time DIA will be combined with ion mobility as a second separation parameter combined with the regular liquid chromatography separation of peptides.

DIA is applied on non-fractionated samples and is based on label-free quantification. This increases the throughput and decreases the consumable demands, while also reduces costs and efforts of sample handling. DIA requires more instrument time, due to individual sample analyzed without labels.

Moreover, the DIA method has been shown to generate an overlapping proteome analysis across different samples, which might reduce the problem of missing values in the analysis. In the context of DIA data, a digital record is generated and queried against an existing spectral library used to extract mixed peptide peak signals.

“The usage of proteome analysis is now catalyzed by ion mobility separation and  data-independent acquisition (DIA-MS) together by Parallel Reaction Monitoring (PRM) analysis. There are new technical developments in the proteomics field, and this is what we are now investing in.”

Carina Sihlbom, unit manager at Proteomics Core Facility