Department Seminar Series - Kristen M Naegle, Ph.D

Towards precision medicine: A new algorithm for inferring kinase activities

Kinases represent the largest class of FDA approved drugs for oncology. However, major challenges exist in cancer treatment, such as failure to respond to therapy and the development of tumor resistance to therapy. More accurate and efficacious targeting would be significantly helped if we had better ways to identify dysregulated kinases or kinase activity profiles of tumors. In this talk, I’m going to share our new algorithmic approach, KSTAR, to infer kinase activities from phosphoproteomic data. The core of KSTAR is a graph and statistical approach to measure the overrepresentation of phosphorylation sites from a kinase’s network that were observed within a given phosphoproteomic profile of a cell or tumor sample. KSTAR’s major algorithmic advances are from graph-based approaches that harness kinase-substrate prediction algorithms in a bias- and error-aware manner. I will share how KSTAR’s activity score and statistical values are helpful for making sparse phosphoproteomic data more comparable and can complement current clinical standards of diagnosis – identifying false positive HER2 breast cancer cases and identifying cases of HER2-negative breast cancer cases that have basal HER2-activity.

Kristen M Naegle is an associate professor of Biomedical Engineering, Computer Science and Engineering, and resident member of the Center for Public Health Genomics at the University of Virginia. Dr. Naegle was assistant professor of Biomedical Engineering and Computer Science and Engineering (courtesy appointment) at Washington University in St. Louis from 2012 to 2018. Dr. Naegle received her Ph.D. in 2010 from the Massachusetts Institute of Technology in Biological Engineering and was subsequently trained as a postdoctoral associate at the Koch Institute for Integrative Cancer Research. Prior to her Ph.D. training, Dr. Naegle earned a B.S. and a M.S. in Electrical Engineering from University of Washington. Her lab builds molecular toolkits and develops algorithms to understand the role of tyrosine phosphorylation within proteins and protein networks. Dr. Naegle’s work has been funded by the NCI, NIGMS, and NAIAD.

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