Expanding horizons: Maximizing the potential of targeted protein degradation

Why you should be using MS-based proteomics in hematology

Hematology presents unique challenges for researchers aiming to pinpoint specific biomarkers or unravel the underlying mechanisms of diseases related to the blood.  


One major challenge is the dynamic range of proteins found in blood samples. Another difficulty is sample heterogeneity, stemming from variations in the composition of blood specimens among individuals. The various sample collection methods used for blood samples, along with changes in storage and handling, can also create complications. 


Conventional techniques used to study the blood and its related tissues, such as immunoassays, often grapple with limitations in sensitivity and specificity. Ultimately, this reduces their ability to comprehensively profile the range of proteins in a sample or overcome the complexities associated with sample heterogeneity.  


Mass spectrometry (MS) is a powerful tool for navigating these challenges. Biognosys’ MS-based plasma proteomics services provide a robust platform enabling high-throughput analysis of a wide range of proteins with enhanced sensitivity and specificity that minimizes the impact of sample collection on data quality. 


No more antibodies  


Immunoassays rely on predefined antibodies, which limits their scope to known targets, and antibody development can be time-consuming and costly. 


MS-based proteomics circumnavigates the use of predefined antibodies, instead measuring the mass-to-charge ratio of ionized peptides in a sample. This provides a broad and unbiased view of the entire proteome and allows for much easier scale up to larger biomarker studies using relative or absolute quantification.  


Immunoassays can also suffer from high variability and poor reproducibility. Using different antibodies for the same target analyte can give rise to different results, and these antibodies can also cross-react with off-target substances to produce false-positive or false-negative results.  


By contrast, MS-based methods are highly reproducible. As mass spectrometry is based on well-established protocols, it does not suffer from the variability introduced by different antibodies. MS also exhibits greater specificity than immunoassays, as it can distinguish between closely related molecules based on their mass and charge. This minimizes the risk of interference and improves the accuracy of results.  


For example, Biognosys’ TrueDiscovery® platform can robustly and reproducibly quantify up to 7,000 proteins in human plasma, as well as in peripheral blood mononuclear cells and sorted cells, using data-independent acquisition (DIA) at a reproducibility rate of over 98%. 


Aptamer-based methods, which do not use antibodies, are one potential alternative to immunoassays. However, aptamers lack specificity, meaning the data collected from these approaches often needs to be validated by complementary methods such as MS. Our TrueDiscovery workflows can also be used to analyze post-translational modifications (PTMs) – valuable disease markers that cannot be measured using traditional methods.  


Remarkable depth at high throughput 


Besides their reliance on antibodies, immunoassays are also only able to provide information on a limited set of preselected targets, while MS-based proteomics enables the comprehensive analysis of thousands of proteins. In hematology research, deep proteome analysis is particularly valuable as it allows researchers to uncover intricate molecular mechanisms and identify subtle changes in protein expression.  


With the recent integration of the Bruker timsTOF into our TrueDiscovery workflows, we can now offer versatile plasma analysis (Lite, DeepHT, UltraDeep) that balances depth and speed to address researchers’ specific biological questions. This ensures efficient project completion while maintaining consistent reproducibility across various sample sets. Our latest DeepHT workflow achieves proteome coverage of up to 4,500 proteins in plasma samples with unprecedented throughput.  


In certain hematology research scenarios, the available cell input may be extremely limited. Thankfully, advances in high-resolution MS mean that even with minimal cell inputs, highly sensitive protein measurements are possible.  


Biognosys’ TrueDiscovery platform, built on high-throughput Hyper Reaction Monitoring (HRM) mass spectrometry, robustly identifies and quantifies proteins using as few as 10,000 cells. This facilitates the high-dimensional phenotypic characterization of sorted immune cell populations in hematological research. Our platform can also be used to isolate and analyze blood-derived exosomes, as in our collaboration with the University of Zurich, the Université de Fribourg – Universität Freiburg, and Stanford University. 


Accurate quantification  


Precise quantification is crucial to ensure robust findings. MS-based proteomics methods such as HRM, as well as targeted approaches such as PRM not only match but often surpass current gold standard approaches. For example, our latest TrueSignature® hyperplex workflow offers absolute quantification of up to 800 protein targets. 


In Figure 1, a comparative analysis of the sensitivity between HRM, TrueSignature PRM, and QIFI flow cytometry demonstrates a high correlation in expression quantification. Notably, the correlation is much higher than using transcriptomic readouts, which again highlights the benefits of substituting immunoassays or transcriptomic approaches with MS-based proteomics methods.  

Figure 1: Correlation between the results obtained using the gold standard QIFI® (flow cytometry) and (A) the TrueDiscovery® HRM MS workflow, (B) the TrueSignature® PRM MS workflow 


Unleash the power of mass spectrometry in hematology  


The challenges faced in hematology research demand advanced and precise proteomic techniques. Conventional techniques such as immunoassays may seem like the easy option, but the high sensitivity of MS-based proteomics approaches, especially in scenarios with limited cell input, promises to elevate the depth and precision of hematology research and pave the way for more nuanced insights and discoveries.  


Luckily, Biognosys has more than a decade of experience in plasma proteomics to help you take advantage of these advanced mass spectrometry approaches with market-leading proteome coverage. We’re the perfect partner to help you on your journey to generating robust, reliable data from any number of samples, from small pilot studies through to clinical trials.   


Click here for more information on our plasma services, or get in contact to find out how we can help. 

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