Probability Seminar
Abstract: Rare events are quite common in our daily lives -- chemical reactions, kinetics phase transitions, or regime changes in climate are a few examples among many others. To describe such events, Chemists and Physicists usually invoke concepts such as the reaction coordinate or the free energy of the reaction. Assuming that the dynamics of the system can be described a Markov chain or a stochastic differential equation, it is possible to give a precise meaning to these concepts using the framework of Large Deviation Theory, at least in the limit when the amplitude of the noise becomes vanishingly small. This limit, however, is often far from realistic in practice. In this talk, I will explain how to describe the mechanism of a reaction which occurs at finite amplitude of the noise, starting by giving a precise definition of what such a question actually means. I will then show how this theoretical framework can be put to use to design numerical algorithms to describe the transition pathways and the rate of rare reactive events. This will be illustrated by several examples, including one of biochemical interest: the hydrophobic collapse of a solvated polymeric chain described by molecular dynamics.
Center for Computational Molecular Biology
Abstract: Dr. Collins will present on the use of array comparative genomic hybridization (aCGH) and end sequence profiling (ESP) for the development of novel biomarkers and therapeutic targets for cancer. Prostate cancer is amongst the prevalent cancers in the Western world and is increasing in incidence. PSA screening for prostate cancer has resulted in stage migration so that increasingly tumors are detected at an earlier stage. Nonetheless the percent age of men diagnosed with tumors at an intermediate risk of progressing to metastasis has remained relatively constant at ~ 25% and there is little change in the outcome statistics for this group. Therefore, it is critical that biomarkers be developed that can identify men in this group who can safely delay or avoid definitive therapy, alleviating the problem of over treatment. Dr. Collins laboratory has employed unique tumor cohorts and aCGH to identify genome based biomarkers that may be capable of dichotomizing this group of patients. To refine and advance this assay to the clinic whole genome amplification methods are being developed to enable analysis of tumor biopsies on Agilent oligonucleotide arrays. Dr. Collins will review progress and discuss the challenges of this type of research. A problem with array-based analyses is that it is very difficult for them to detect tumor specific biomarkers and drug targets such as the BCR-ABL fusion in CML. In addition, they are blind to heterogeneity. To overcome these limitations Drs. Collins and Volik invented ESP with the explicit goals of determining the structural organization of tumor genomes and transcriptomes. Progress made in the application of ESP to breast cancer cell lines and multiple tumor types will be presented. Specifically, data will be presented showing the structural organization of tumor genomes, the frequency and spectrum of mutations, molecular heterogeneity, validation of genome breakpoints, and detection of tumor-specific fusion genes and transcripts. In addition, ideas will be explored for a genome project based on ESP, and advancement of ESP to the clinic using next generation sequencing technologies.
Scientific Computing Seminar
PDE Seminar
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