Modeling DNA methylation dynamics with approaches from phylogenetics

Methylation of CpG dinucleotides is a prevalent epigenetic modification that is required for proper development in vertebrates, and changes in CpG methylation are essential to cellular differentiation. Genome-wide DNA methylation assays have become increasingly common, and recently distinct stages across differentiating cellular lineages have been assayed. How- ever, current methods for modeling methylation dynamics do not account for the dependency structure between precursor and dependent cell types. We developed a continuous-time Markov chain approach, based on the observation that changes in methylation state over tissue differentiation can be modeled similarly to DNA nucleotide changes over evolutionary time. This model explicitly takes precursor to descendant relationships into account and enables inference of CpG methylation dynamics. To illustrate our method, we analyzed a high-resolution methylation map of the differentiation of mouse stem cells into several blood cell types. Our model can successfully infer unobserved CpG methylation states from observations at the same sites in related cell types (90% correct), and this approach more accurately reconstructs missing data than imputation based on neighboring CpGs (84% correct). Additionally, the single CpG resolution of our methylation dynamics estimates enabled us to show that DNA sequence context of CpG sites is informative about methylation dynamics across tissue differentiation. Finally, we identified genomic regions with clusters of highly dynamic CpGs and present a likely functional example. Our work establishes a framework for inference and modeling that is well-suited to DNA methylation data, and our success suggests that other methods for analyzing DNA nucleotide substitutions will also translate to the modeling of epigenetic phenomena.Comment: 8 pages, 5 figure

Classroom Games: A Prisoner's Dilemma

Game theory is often introduced in undergraduate courses in the context of a prisoner's dilemma paradigm, which illustrates the conflict between social incentives to cooperate and private incentives to defect. We present a very simple card game that efficiently involves a large number of students in a prisoner's dilemma. The extent of cooperation is affected by the payoff incentives and by the nature of repeated interaction. The exercise can be used to stimulate a discussion of a wide range of topics such as bankruptcy, quality standards, or price competition.prisoner's dilemma, game theory, experimental economics, classroom experiments

VOLARE: Adaptive Web Service Discovery Middleware for Mobile Systems

With the recent advent and widespread use of smart mobile devices, the flexibility and versatility offered by Service Oriented Architecture's (SOA) makes it an ideal approach to use in the rapidly changing mobile environment. However, the mobile setting presents a set of new challenges that service discovery methods developed for nonmobile environments cannot address. The requirements a mobile client device will have from a Web service may change due to changes in the context or the resources of the client device. In a similar manner, a mobile device that acts as a Web service provider will have different capabilities depending on its status, which may also change dramatically during runtime. This paper introduces VOLARE, a middleware-based solution that will monitor the resources and context of the device, and adapt service requests accordingly. The same method will be used to adapt the Quality of Service (QoS) levels advertised by service providers, to realistically reflect each provider's capabilities at any given moment. This approach will allow for more resource-efficient and accurate service discovery in mobile systems and will enable more reliable provider functionality in mobile devices

A survey of music activities in Veterans Administration Hospital in the New England area.

Thesis (M.A.)--Boston Universit