Systems biology approach to discover the proteoform drivers of disease

Description:
The post-genomic era is marked by the development of technologies which have revealed the astonishing molecular diversity of gene products. Diverse protein forms, or “proteoforms”, can arise from post-transcriptional mechanisms such as alternative splicing and/or post-transcriptional mechanisms such as phosphorylation. The existence of so many distinct proteoforms being produced from the same genetic locus prompts revisiting of the traditional notion of the “gene”. It motivates the urgent need to enumerate all healthy and disease-associated proteoforms in human and to assess their functional significance.
At the Sheynkman lab, we aim to accelerate the discovery of clinically actionable proteoforms by integrating cutting-edge analytical and computational approaches from systems genetics, proteogenomics, and network biology. This precision medicine approach is applied in a disease agnostic manner to elucidate proteoform-driven rewiring events in cardiovascular disease, neurological disorders, and cancer. Currently, we are focusing our efforts on the detection and characterization of protein isoforms (or splice forms), a tractable goal based on the state of the field. However, this framework should be directly applicable to analysis of proteoforms.
In this seminar, Dr. Sheynkman will present approaches for 1) enhanced detection of protein isoforms, using a recently developed “long read proteogenomics” approach, 2) an integrative systems genetics approach for nominating protein isoform drivers of disease, and 3) computational predictive and interactomics approaches to dissect the mechanism by which protein isoforms drive phenotypic changes. The lab aims to be a collaborative link in developing these ideas across fields to support the vision of the Human Proteoform Project.

Speaker: Gloria Sheynkman - University of Virginia School of Medicine