Proteomics

Proteomics plays a vital role in understanding disease mechanisms and advancing drug discovery by providing detailed insights into protein function, post-translational modifications and protein-protein interactions. Its ability to identify disease biomarkers, elucidate pathogenic processes, validate drug targets and personalize treatment regimens makes it an indispensable tool in the quest for more effective and safer therapies.

Proteins are the primary targets for the majority of drugs, however, comprehensive, system-wide approaches to monitor protein activity and function are still not fully leveraged in drug discovery and clinical research.

Challenges in Protein Sample Preparation and Analysis

While proteomics brings us closer to understanding the phenotype than genomics or transcriptomics alone, it has yet to achieve the same level of throughput as RNA and DNA sequencing. It is largely due to intrinsic challenges in protein sample preparation and analysis. The human proteome, estimated to consist of around 20,000 to 25,000 protein-coding genes, is further diversified by alternative splicing and post-translational modifications, resulting in hundreds of thousands of protein variants.

Unlike nucleic acids, proteins cannot be amplified through techniques like PCR, so proteomic analyses must work directly with the native content, encompassing both low- and high-abundance proteins, which limits method sensitivity.

Manual handling in protein sample preparation is a complex and labor-intensive process that demands precision, skill, and careful attention to detail. From extraction and quantification to fractionation and quality control, each step must be performed meticulously to ensure that the obtained results are reproducible and accurately reflect the protein content of the sample.

Finally, proteomics typically incurs higher costs per sample compared to the more standardized and scalable processes in genomics, limiting its adoption.

Driving the Proteomics Field Forward

Despite these hurdles, ongoing innovations are driving the field forward. Advances in liquid handling automation, analytical instrumentation and the development of sophisticated chemistries are progressively enhancing the throughput, sensitivity, and reliability of proteomics studies.

Affinity-based proteomic technologies are receiving increasing attention, particularly in plasma proteomics. The proximity extension assay (PEA) developed by Olink Proteomics is prime examples, using pairs of oligonucleotide-labeled antibodies that bind to adjacent epitopes on target proteins. The proximity of these labels allows for DNA amplification, which is then quantified to determine protein levels. PEA’s remarkable sensitivity enables the detection of low-abundance proteins that might be missed by other techniques. This enables the simultaneous analysis of thousands of proteins from a minute amount of sample, making large-scale studies more feasible. Our proven miniaturization technology bolsters high-throughput protein biomarker discovery and population-scale proteogenomics with the Olink Explore platform (ref 1-2).

Over the past decade, Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) MS has achieved laser scanning speeds of under one second per sample, dramatically reducing acquisition times. MALDI-TOF MS requires very small sample volumes, facilitating assay miniaturization and cost reduction. When combined with automated low-volume liquid handling systems, such as mosquito LV, these features make MALDI-TOF MS assays particularly well-suited for robust high-throughput screening (HTS) (ref 3-4).

Cryo-electron microscopy (cryo-EM) has also ushered in a new era of scientific discovery, offering increasingly higher-resolution structural information. Advances in both hardware and software for both sample preparation and analysis have now opened up the technique to more widespread adoption in basic research and drug discovery (ref 5-6).

Related products

Our suite of automated liquid handling solutions, mosquito, firefly, dragonfly and chameleon, enhances the reliability and efficiency of proteomics research: