172003
Reconstructing the Evolutionary History of Complex Human Gene Clusters
Clusters of genes that evolved from single progenitors via repeated segmental duplications present significant challenges to the generation of a truly complete human genome sequence. Such clusters can confound both accurate sequence assembly and downstream computational analysis, yet they represent a hotbed of functional innovation, making them of extreme interest. We have developed an algorithm for reconstructing the evolutionary history of gene clusters using only human genomic sequence data. This method allows the tempo of large-scale evolutionary events in human gene clusters to be estimated, which in turn will facilitate primate comparative sequencing studies that will aim to reconstruct their evolutionary history more fully.
42884670
Eulerian path methods for multiple sequence alignment
With the rapid increase in the size of genome sequence databases, the multiple sequence alignment problem is increasingly important and often requires the alignment of a large number of sequences. Beginning in 1975, many heuristic algorithms have been created to improve the speed of computation and the quality of alignment. We introduce a novel approach that is fundamentally distinct from all currently available methods. Our motivation comes from the Eulerian method for fragment assembly in DNA sequence determination, that transforms all the DNA sequencing fragments into a de Bruijn graph and then reduces sequence assembly to a Eulerian path problem.
32462907
Alignment of Optical Maps
We introduce a new scoring method for calculation of alignments of optical maps. Missing cuts, false cuts, and sizing errors present in optical maps are addressed by our alignment score through calculation of corresponding likelihoods. The size error model is derived through the application of Central Limit Theorem and validated by residual plots collected from real data. Missing cuts and false cuts are modeled as Bernoulli and Poisson events, respectively, as suggested by previous studies. Likelihoods are used to derive an alignment score through calculation of likelihood ratios for a certain hypothesis test. This allows us to achieve maximal descriminative power for the alignment score. Our scoring method is naturally embedded within a well known DP framework for finding optimal alignments.
29942985
Poisson approximation for significance in genome-wide ChIP-chip tiling arrays
MOTIVATION
A genome-wide ChIP-chip tiling array study requires millions of simultaneous comparisons of hybridization for significance. Controlling the false positive rate in genome-wide tiling array studies is very important, because the number of computationally identified regions can easily go beyond the capability of experimental verification. No accurate and efficient method exists for evaluating statistical significance in tiling arrays. The Bonferroni method is overly conservative and the permutation test is time consuming for genome-wide studies.


RESULT
Motivated by the Poisson clumping heuristic, we propose an accurate and efficient method for evaluating statistical significance in genome-wide ChIP-chip tiling arrays. The method works accurately for any large number of multiple comparisons, and the computational cost for evaluating P-values does not increase with the total number of tests. Based on a moving window approach, we demonstrate how to combine results using various window sizes to increase the detection power while maintaining a specified type I error rate. We further introduce a new false discovery rate control that is more appropriate in measuring the false proportion of binding intervals in tiling array analysis. Our method is general and can be applied to many large-scale genomic and genetic studies.


AVAILABILITY
http://www.stat.psu.edu/~yuzhang/pass.tar
12263549
Tree-guided Bayesian inference of population structures
MOTIVATION
Inferring population structures using genetic data sampled from a group of individuals is a challenging task. Many methods either consider a fixed population number or ignore the correlation between populations. As a result, they can lose sensitivity and specificity in detecting subtle stratifications. In addition, when a large number of genetic markers are used, many existing algorithms perform rather inefficiently.


RESULT
We propose a new Bayesian method to infer population structures using multiple unlinked single nucleotide polymorphisms (SNPs). Our approach explicitly considers the population correlation through a tree hierarchy, and treat the population number as a random variable. Using both simulated and real datasets of worldwide samples, we demonstrate that an incorporated tree can consistently improve the power in detecting subtle population stratifications. A tree-based model often involves a large number of unknown parameters, and the corresponding estimation procedure can be highly inefficient. We further implement a partition method to analytically integrate out all nuisance parameters in the tree. As a result, our method can analyze large SNP datasets with significantly improved convergence rate.


AVAILABILITY
http://www.stat.psu.edu/~yuzhang/tips.tar.
12935102
Whole-Genome Analysis of Gene Conversion Events
Gene conversion events are often overlooked in analyses of genome evolution. In a conversion event, an interval of DNA sequence (not necessarily containing a gene) overwrites a highly similar sequence. The event creates relationships among genomic intervals that can confound attempts to identify orthologs and to transfer functional annotation between genomes. Here we examine 1,112,202 paralogous pairs of human genomic intervals, and detect conversion events in about 13.5% of them. Properties of the putative gene conversions are analyzed, such as the lengths of the paralogous pairs and the spacing between their sources and targets. Our approach is illustrated using conversion events in the beta-globin gene cluster.
2479481
Gene Regulatory Network Construction Using Dynamic Bayesian Network (DBN) with Structure Expectation Maximization (SEM)
Discovering gene relationship from gene expression data is a hot topic in the post-genomic era. In recent years, Bayesian network has become a popular method to reconstruct the gene regulatory network due to the statistical nature. However, it is not suitable for analyzing the time-series data and cannot deal with cycles in the gene regulatory network. In this paper we apply the dynamic Bayesian network to model the gene relationship in order to overcome these difficulties. By incorporating the structural expectation maximization algorithm into the dynamic Bayesian network model, we develop a new method to learn the regulatory network from the S. Cerevisiae cell cycle gene expression data. The experimental results demonstrate that. the accuracy of our method outperforms the previous work.
12120268
Performance of Coded pi/2 NS-8QAM Modulation
Spectrum and Bit Error Rate (BER) performance of a coded π/2 phase shift Non-Square (NS) 8 Quadrature Amplitude Modulation (QAM) system are studied in this letter. The modulation process of this scheme removes all 180° phase shift between adjacent constellation points and contains inherent memory which can be treated as a type of inner coding in coded system. Simulation results show that this modulation scheme has much lower spectrum regrowth and better BER performance when passing through nonlinear channel compared with conventional mode.
18862565
Inferring Gene Regulatory Networks from Multiple Data Sources Via a Dynamic Bayesian Network with Structural EM
Using our dynamic Bayesian network with structural Expectation Maximization (SEM-DBN), we develop a new framework to model gene regulatory network from both gene expression data and transcriptional factor binding site data. Only based on mRNA expression data, it is not enough to accurately estimate a gene network. It is difficult for us to estimate a gene network accurately only with the mRNA expression data. In this paper, we use the transcription factor binding location data in order to introduce the prior knowledge to SEM-DBN model. Gene expression data are also exploited specifically for likelihood. Meanwhile, we incorporate the prior knowledge into every learning step by SEM rather than only learning from the very beginning, which can compensate the attenuation of the effect with location data. The effectiveness of our proposed method is demonstrated through the analysis of Saccharomyces cerevisiae cell cycle data. The combination of heterogeneous data from multiple sources ensures that our results are more accurate than those recovered from only gene expression data alone.
1131898
A Novel Spatial Autocorrelation Model of Shadow Fading in Urban Macro Environments
In this paper, we propose a novel spatial autocorrelation model of the shadow fading process in urban macro environments. The proposed model is based on the empirical results obtained from extensive wideband radio channel measurement campaigns at 2.35 GHz in an urban area of a typical medium-sized Chinese city. The shadow fading component was extracted assuming a single-slope log-distance path loss model. The consistency with the level crossing theory of Gaussian processes is achieved by an implicit constraint on the parameters of the model. The proposed model gives a better fit to the empirical results in individual measurement routes than the widely reported exponential and double exponential models. An heuristic explanation of the proposed autocorrelation property is also presented.
1863221
A fast and stable approach for restoration of warped document images
We present a framework for acquiring and restoring images of warped documents to their original planar shapes. Image capturing of warped documents often results in warped images. Most digital restoration approaches make use of 2D image processing methods which are dependent on the content of the images. Some recent work attempts to remove this constraint by working directly on the 3D shape of the warped documents. In our framework, we improve on this recent approach to make it more efficient and stable. First we capture the warped surface representation through a set of active lighting from a laser range scanner onto the document surface. This gives us an accurate 3D representation of the document shape. Next by using a stick constraint and a stable numerical integrator, we can digitally flatten the 3D model to a planar shape. This simple approach avoids potential instability problem and is fast. Restoration results for a few types of warped documents are demonstrated and a significant improvement over the original images can be observed.