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      Pooling Design and Bias Correction in DNA Library Screening

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          Abstract

          We study the group test for DNA library screening based on probabilistic approach. Group test is a method of detecting a few positive items from among a large number of items, and has wide range of applications. In DNA library screening, positive item corresponds to the clone having a specified DNA segment, and it is necessary to identify and isolate the positive clones for compiling the libraries. In the group test, a group of items, called pool, is assayed in a lump in order to save the cost of testing, and positive items are detected based on the observation from each pool. It is known that the design of grouping, that is, pooling design is important to %reduce the estimation bias and achieve accurate detection. In the probabilistic approach, positive clones are picked up based on the posterior probability. Naive methods of computing the posterior, however, involves exponentially many sums, and thus we need a device. Loopy belief propagation (loopy BP) algorithm is one of popular methods to obtain approximate posterior probability efficiently. There are some works investigating the relation between the accuracy of the loopy BP and the pooling design. Based on these works, we develop pooling design with small estimation bias of posterior probability, and we show that the balanced incomplete block design (BIBD) has nice property for our purpose. Some numerical experiments show that the bias correction under the BIBD is useful to improve the estimation accuracy.

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              CCCP Algorithms to Minimize the Bethe and Kikuchi Free Energies: Convergent Alternatives to Belief Propagation

              A Yuille (2002)
              This article introduces a class of discrete iterative algorithms that are provably convergent alternatives to belief propagation (BP) and generalized belief propagation (GBP). Our work builds on recent results by Yedidia, Freeman, and Weiss (2000), who showed that the fixed points of BP and GBP algorithms correspond to extrema of the Bethe and Kikuchi free energies, respectively. We obtain two algorithms by applying CCCP to the Bethe and Kikuchi free energies, respectively (CCCP is a procedure, introduced here, for obtaining discrete iterative algorithms by decomposing a cost function into a concave and a convex part). We implement our CCCP algorithms on two- and three-dimensional spin glasses and compare their results to BP and GBP. Our simulations show that the CCCP algorithms are stable and converge very quickly (the speed of CCCP is similar to that of BP and GBP). Unlike CCCP, BP will often not converge for these problems (GBP usually, but not always, converges). The results found by CCCP applied to the Bethe or Kikuchi free energies are equivalent, or slightly better than, those found by BP or GBP, respectively (when BP and GBP converge). Note that for these, and other problems, BP and GBP give very accurate results (see Yedidia et al., 2000), and failure to converge is their major error mode. Finally, we point out that our algorithms have a large range of inference and learning applications.
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                Author and article information

                Journal
                2010-04-22
                2010-04-25
                Article
                1004.4041
                25529f3f-bcb0-4553-abc0-3099b084ac39

                http://arxiv.org/licenses/nonexclusive-distrib/1.0/

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                Custom metadata
                18 pages, 1 figure, 8 tables, submitted.
                stat.CO q-bio.QM

                Quantitative & Systems biology,Mathematical modeling & Computation
                Quantitative & Systems biology, Mathematical modeling & Computation

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