High-Resolution Molecular Interactome Perturbations and Functional Variomics to Enhance Precision Medicine

Tuesday, October 16, 2018 -
2:00pm to 3:00pm
The FUNG Auditorium
Song (Stephen) Yi

Assistant Professor of Oncology

Director of Bioinformatics, Developmental Therapeutics Lab

 LiveSTRONG Cancer Institutes and Dell Medical School

University of Texas at Austin

High-Resolution Molecular Interactome Perturbations and Functional Variomics to Enhance Precision Medicine

Abstract: 

In the past decade, genome and exome sequencing projects have identified thousands of genetic variants in patients across a large number of Mendelian disorders, complex traits and cancer types. However, the explosion of genomic information has left many fundamental questions regarding genotype-phenotype relationships unresolved. One critical challenge is to distinguish causal disease mutations from non-pathogenic polymorphisms. Even when causal mutations are identified, the functional consequence of such mutations is often elusive. The absence of efficient high-throughput analyses of disease variants has therefore created a bottleneck in understanding the underlying disease mechanisms. We show that genes and gene products do not function in isolation but interact with each other as components of complex interactome networks of various macromolecules (DNA, RNA or proteins) and metabolites. In this seminar, I describe a systematic ”fucntional variomics” approach to investigate genetic variant-specific effects on molecular interactions at large scale across diverse human diseases. Remarkably, in comparison to non-disease polymorphisms, disease mutations are more likely to associate with interaction perturbations. I will present the extent to which and how single-nucleotide disease mutations cause protein interaction alterations. We have been able to find different mutations of the same gene give rise to different interaction profiles, accounting for distinct disease outcomes. We recently characterized RNA splicing alterations caused by patient-specific mutations, and revealed an interaction perturbation landscape in cancer. Together, we provide unprecedented evidence for widespread interaction-specific perturbations across a broad spectrum of human diseases. Our approach is insightful in prioritizing disease-causing variants, and uncovering patient mutation-specific disease mechanisms at a base-pair resolution, a critical step towards personalized precision medicine. 

Bio: 

Dr. Song (Stephen) Yi is an Assistant Professor of Oncology and Director of Bioinformatics, Developmental Therapeutics Lab, at LiveSTRONG Cancer Institutes and Dell Medical School of The University of Texas at Austin. He is a joint faculty member at the MD Anderson Cancer Center. He is also an affiliated faculty with Department of Biomedical Engineering, and Institute of Cellular and Molecular Biology. Dr. Yi has received multiple academic honors and awards, including the NIH/NCI Transition Career Development Award and Dean’s Distinguished Dissertation Award. Dr. Yi received his undergraduate’s degree from Peking University, and doctoral degree from University of Iowa. He completed a postdoctoral fellowship at Harvard Medical School with Susan Lindquist and Marc Vidal. As a faculty member, Dr. Yi’s laboratory is productive and well-funded. Using his new ‘functional variomics’ and systems network biology platforms, Dr. Yi’s lab combines computational and experimental expertise to build a quantitative understanding of molecular interactome networks in disease. Currently, Dr. Yi’s research interests include cancer signaling, tumor immunology and evolution, synthetic lethality and drug resistance, next-gen sequencing analysis and multi-omics network biology. He is also dedicated in constantly developing new technologies to address these questions.