A Knowledge Gradient Policy for Sequencing Experiments to Identify the Structure of RNA Molecules Using a Sparse Additive Belief Model

We present a sparse knowledge gradient (SpKG) algorithm for adaptively selecting the targeted regions within a large RNA molecule to identify which regions are most amenable to interactions with other molecules. Experimentally, such regions can be inferred from fluorescence measurements obtained by binding a complementary probe with fluorescence markers to the targeted regions. We use a biophysical model which shows that the fluorescence ratio under the log scale has a sparse linear relationship with the coefficients describing the accessibility of each nucleotide, since not all sites are accessible (due to the folding of the molecule). The SpKG algorithm uniquely combines the Bayesian ranking and selection problem with the frequentist $\ell_1$ regularized regression approach Lasso. We use this algorithm to identify the sparsity pattern of the linear model as well as sequentially decide the best regions to test before experimental budget is exhausted. Besides, we also develop two other new algorithms: batch SpKG algorithm, which generates more suggestions sequentially to run parallel experiments; and batch SpKG with a procedure which we call length mutagenesis. It dynamically adds in new alternatives, in the form of types of probes, are created by inserting, deleting or mutating nucleotides within existing probes. In simulation, we demonstrate these algorithms on the Group I intron (a mid-size RNA molecule), showing that they efficiently learn the correct sparsity pattern, identify the most accessible region, and outperform several other policies

Identifying efficient solutions via simulation: myopic multi-objective budget allocation for the bi-objective case

Simulation optimisation offers great opportunities in the design and optimisation of complex systems. In the presence of multiple objectives, there is usually no single solution that performs best on all objectives. Instead, there are several Pareto-optimal (efficient) solutions with different trade-offs which cannot be improved in any objective without sacrificing performance in another objective. For the case where alternatives are evaluated on multiple stochastic criteria, and the performance of an alternative can only be estimated via simulation, we consider the problem of efficiently identifying the Pareto-optimal designs out of a (small) given set of alternatives. We present a simple myopic budget allocation algorithm for multi-objective problems and propose several variants for different settings. In particular, this myopic method only allocates one simulation sample to one alternative in each iteration. This paper shows how the algorithm works in bi-objective problems under different settings. Empirical tests show that our algorithm can significantly reduce the necessary simulation budget

Philosophy and the practice of Bayesian statistics

A substantial school in the philosophy of science identifies Bayesian inference with inductive inference and even rationality as such, and seems to be strengthened by the rise and practical success of Bayesian statistics. We argue that the most successful forms of Bayesian statistics do not actually support that particular philosophy but rather accord much better with sophisticated forms of hypothetico-deductivism. We examine the actual role played by prior distributions in Bayesian models, and the crucial aspects of model checking and model revision, which fall outside the scope of Bayesian confirmation theory. We draw on the literature on the consistency of Bayesian updating and also on our experience of applied work in social science. Clarity about these matters should benefit not just philosophy of science, but also statistical practice. At best, the inductivist view has encouraged researchers to fit and compare models without checking them; at worst, theorists have actively discouraged practitioners from performing model checking because it does not fit into their framework.Comment: 36 pages, 5 figures. v2: Fixed typo in caption of figure 1. v3: Further typo fixes. v4: Revised in response to referee

Economic Analysis of Simulation Selection Problems

Ranking and selection procedures are standard methods for selecting the best of a finite number of simulated design alternatives based on a desired level of statistical evidence for correct selection. But the link between statistical significance and financial significance is indirect, and there has been little or no research into it. This paper presents a new approach to the simulation selection problem, one that maximizes the expected net present value of decisions made when using stochastic simulation. We provide a framework for answering these managerial questions: When does a proposed system design, whose performance is unknown, merit the time and money needed to develop a simulation to infer its performance? For how long should the simulation analysis continue before a design is approved or rejected? We frame the simulation selection problem as a “stoppable” version of a Bayesian bandit problem that treats the ability to simulate as a real option prior to project implementation. For a single proposed system, we solve a free boundary problem for a heat equation that approximates the solution to a dynamic program that finds optimal simulation project stopping times and that answers the managerial questions. For multiple proposed systems, we extend previous Bayesian selection procedures to account for discounting and simulation-tool development costs

BAYES' ESTIMATES OF THE DOUBLE HURDLE MODEL IN THE PRESENCE OF FIXED COSTS

We present a model of market adoption (participation) where the presence of non-negligible fixed costs leads to non-zero censoring of the traditional double-hurdle regression. Fixed costs arise due to household resources that must be devoted a priori to the decision to participate in the market. These costs-usually a cost of time-motivate two-step decision-making and focus attentions on the minimum-efficient scale of operations (the minimum amount of milk sales) at which market entry becomes viable. This focus, in turn, motivates a non-zero-censored Tobit regression estimated through routine application of Markov chain Monte Carlo Methods.market participation, fixed costs, double-hurdle model, censored regression., Financial Economics, O1, O11, C34, O13, Q16, D1,