The Scientist Feature: Proteomics 2.0 and Its Impact on Drug Development

While genomics has proved transformative in decoding the genetic underpinnings of disease and remains a cornerstone for drug development today, population-scale discovery has been notably shifting in recent years “beyond the genome,” focusing on complementary data sources that may be leveraged to accelerate the drug development process. This shift has been catalyzed by the observation that, given the largely static nature of the human genome (which is set from conception), genomic measures capture only a minority fraction of population attributable risk for most common human diseases, from cancer to autoimmune disorders.

Genetic Code Versus Zip Code

It has long been appreciated that dynamic non-genetic factors, including external factors such as diet, lifestyle, environment, and toxicants, as well as internal factors including organ physiology, cell-to-cell communication, and tissue repair and remodeling, may have far greater influence on overall health outcomes. As such, there is increasing interest in generating expanded omics datasets, including through transcriptomics, proteomics, and metabolomics, which can read out these effects on health status and disease pathobiology over time.

Direct Measures, Dynamic Insights

Proteomics—the direct measure of proteins expressed by the genome to assess their presence, structures, functions, variants, and interactions—enables us to more directly and deeply understand the dynamic processes contributing to disease and drug response. It provides a comprehensive view of protein activity and the protein modifications that also contribute to and influence the cellular environment. Through proteomics, we can identify functionally relevant drug targets and biomarkers, elucidating the underlying mechanisms of diseases to inform therapeutic strategies.

Initial proteomic surveys of disease have only further confirmed this thesis, from the identification of more than one hundred thousand protein-disease associations to new clinical insights into pharmacotherapeutic mechanisms of action. The expansion of proteomics analysis as a cornerstone of drug development, however, has been limited by technological hurdles, including the necessary sensitivity, specificity, and speed of measure needed to perform comprehensive protein measures at scale, across more studies and sample matrices, until quite recently.

Innovations Enabling Proteomics 2.0

Proteomic technologies and methodologies are today evolving at a rapid pace, progressively unlocking our ability to study a broader landscape of proteins and their isoforms. These key innovations, particularly in mass spectrometry-based proteomics, have converged to transform the utility of proteomics in drug discovery and development processes in just a short time and have important implications for drug discovery and development processes by enabling the following…