Bioacoustics Research Lab
University of Illinois at Urbana-Champaign | Department of Electrical and Computer Engineering | The Department of Bioengineering  Wednesday, November 22nd, 2017
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Mechanistic Models for Radiation-Induced Neoplastic Transformation: Bayesian Approach to Model Characterization

By Bobby Scott, Ph.D.

Lovelace Respiratory Research Institute
Albuquerque, NM

This presentation will focus on mathematical models we have developed for characterizing radiation-induced neoplastic transformation of aneuploid C3H 10 T1/2 cells by low-LET X and gamma rays or high-LET alpha and neutron irradiations (in vitro). The focus of the research is on integrating dosimetry (including microdosimetic), molecular (e.g., genomic damage induction, repair/misrepair, mutations), and cellular effects information (e.g., neoplastic transformation, cell killing). Our models lead to rather complicated analytical solutions that are difficult to reviewuate (parameter estimation problem) using conventional regression methods. We have had some success with the Bayesian inference approach however. Our Bayesian analyses are implemented via what is called Markov chain Monte Carlo (MCMC) methods. We are using BUGS software (windows version) to carry out the MCMC calculations. The MCMC calculations are very challenging. Associated with this work we have introduced the area of biological microdosimetry (paper in press) for low level exposure to ionizing radiation. Some of the rather complicated math associated with our modeling of radiation-induced neoplastic transformation of cells is presented on the web (pdf format) at: http://www.radiation-scott.org/neotrans1.pdf . Application of our modeling approach to real data for neoplastic is also demonstrated on the web (pdf format) at: http://www.radiation-scott.org/bayesian.pdf . The first author, H. Schollnberger, is a postdoctoral participant that has been working with me for over a year now. The model presented for neoplastic transformation is called NEOTRANS1 and does not include cell death (modeled indirectly). A more recent model (NEOTRANS2) includes two modes of cell death (apoptosis and necrotic death) but only apoptosis is considered important at very low radiation doses.



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