The Buzz About (Prote)Omics

Protein biochemistry tells a tale of diverse protein function. These roles – which range from structural stability to catalysis – are not the only source of variability surrounding these molecules, though. Proteins can also be present in vastly differing amounts, and can be altered in terms of their amino acid sequence and co- and post-translational modifications; the depth of the known proteome covers over 10,000 quantified proteins and 10,000¹⁰ proteoforms.

With the above in mind, it’s probably no surprise to hear that capturing protein complexity with accuracy and high throughput is a great challenge. Yet, the technologies behind proteomics are geared to capture this immense landscape of complexity. In fact, the past five years have ushered in many proteomics advances, leading to improved protein coverage, sensitivity, and throughput; we can now cover extremes from single-cell analyses to the processing of hundreds of samples in a single day.

Most excitingly, proteomics, despite its maturity, continues to grow in new ways. As an example: top-down proteomics approaches are expanding to capture the functionally important patterns of protein post-translational modifications. Further examples: the ways in which we can probe three-dimensional protein structure in vivo (important for determining structural changes as a function of disease) are improving; quantification of a protein interaction partners in cells is leading to growing acknowledgement that proteins can choose to stay at home or travel the world; and single-cell proteomics is emerging as a serious tool for studying cell differentiation, evolution, and interactions. 

What’s more, high-throughput methods with automated and highly QCed workflows are allowing proteomics to boom into a large-scale human population science. In these cases, we can conduct consistent analyses of thousands of samples. Using such methods, we are able to study our natural history, disease progression, and responses to therapies (Amanda Hummon discusses a more personalized approach to the latter application here).

The future is bright, but there’s still some space for improvement and innovation in our toolbox. Proteomics promises to answer burning questions about mechanisms in biology, and increased ease of application means that the proteomics buzz continues to grow. Along with other omics approaches (think metabolomics and lipidomics; see “Gurus of Omics”), previously untold knowledge regarding genetic, metabolomic, and environmental influences lies in wait. Perhaps that’s why The Analytical Scientist team was so keen to devote the February issue to the magic of omics… Let’s explore!