Prof. Jacob Odeberg

A: I am a professor in clinically applied proteomics at KTH Royal Institute of Technology, where my research focuses on cardiovascular and thromboembolic disease, particularly the circulating proteome as source of potentially clinically useful biomarkers. I also work as a senior consultant in internal and acute medicine. By combining well-characterized clinical cohorts and study materials with access to advanced mass spectrometry for targeted proteomics, we can bridge the gap between laboratory-based biomarker discovery and clinical validation.

A: One central problem is identifying which patients are at greatest risk of developing venous thromboembolism or having a recurrence. The clinical information available to us does not always capture the underlying biological differences between patients. Circulating proteins may give us a more direct picture of the processes active in an individual patient.

We also work on improving biomarker-based tools for patients with suspected acute VTE. The aim is to make the diagnostic workup faster and more accurate and, where possible, reduce unnecessary imaging.

A: After a first VTE, the clinician has to balance the risk of recurrence against the risk of bleeding from continued anticoagulant treatment. We are still not very good at predicting that balance for an individual patient. Better markers could help identify who is likely to benefit from extended treatment and who can safely stop.

A: Proteins reflect what is happening biologically at the time a sample is taken. In thrombosis, this may include changes in coagulation, inflammation, endothelial function and tissue injury. Mass spectrometry allows us to measure several proteins with high molecular specificity. It is useful both for exploring disease mechanisms and for developing targeted assays once promising candidates have been identified.

A: Discovery studies can identify many interesting associations, but relatively few survive the next steps. Candidates need to be measured accurately in independent populations using assays that are reproducible and suitable for larger studies. They also have to add clinically useful information beyond what we already know from routine tests and patient characteristics. That transition from an interesting signal to a validated and useful measurement is still a major bottleneck.

A: MARTHA is a well-characterized venous thrombosis cohort that has been used extensively to investigate genetic and circulating risk factors. EDITH is a comparable VTE cohort and therefore provides an ideal setting for independent replication. Together, these cohorts allow us to examine predefined protein candidates in clinically relevant patient material across complementary study settings.

We want to determine whether the candidate signals are reproducible, how they relate to recurrence and other clinical characteristics, and whether combinations of proteins are more useful than individual markers for predicting recurrence.

A: At this stage, we need more than relative differences between groups. We need precise and reproducible measurements of selected proteins across many samples. qRePS provides stable-isotope-labelled protein standards that are introduced early in the workflow and generate several reference peptides after digestion. This is particularly relevant for targeted, multiplexed quantification in plasma and for comparing results across larger sample sets.

A: Relative measurements are very useful in discovery, but they can be difficult to compare between experiments, cohorts or laboratories. Absolute quantification gives results in defined concentration units. This makes it easier to evaluate assay performance, compare findings across studies and, in the longer term, establish concentration ranges or thresholds that may be clinically meaningful.

A: With predefined targets, we can assess the analytical performance of each protein and peptide in advance. Internal standards help us detect and control technical variation during sample preparation and MS analysis. This becomes increasingly important in larger cohorts, where samples may be processed over many plates and on different days. A reproducible workflow gives us greater confidence that the differences we observe are biological and not caused by the measurement process.

A: Clinical risk scores capture established risk factors, genetics reflects inherited predisposition, and proteins provide a more dynamic picture of the patient’s current biological state. In the near term, targeted proteomics is most likely to complement existing tools rather than replace them. Combining these different types of information may improve risk stratification and help us make more individualized clinical decisions.

A: First, the analytical method must be well validated. The findings then need to be replicated in independent cohorts, followed by prospective studies showing that the biomarkers add useful information beyond current practice. Ultimately, a biomarker-guided approach should improve clinical decisions or patient outcomes and be practical and cost-effective.

Mass spectrometry is already used routinely for several types of clinical analysis. Targeted MS protein panels for thrombosis could first be introduced in specialized thrombosis centres at university hospitals, for example within prospective studies or early implementation programmes. Broader implementation will probably take several years and will depend on the quality of the clinical evidence.

A: I hope this collaboration will establish a robust path for validating biologically informative protein signatures in clinically relevant cohorts. In the longer term, these signatures could improve individual risk assessment, support treatment decisions and reveal disease mechanisms that may become targets for prevention or therapy.