21795877
An Eulerian Path Approach to Global Multiple Alignment for DNA Sequences
With the rapid increase in the dataset of genome sequences, the multiple sequence alignment problem is increasingly important and frequently involves the alignment of a large number of sequences. Many heuristic algorithms have been proposed to improve the speed of computation and the quality of alignment. We introduce a novel approach that is fundamentally different from all currently available methods. Our motivation comes from the Eulerian method for fragment assembly in DNA sequencing that transforms all DNA fragments into a de Bruijn graph and then reduces sequence assembly to a Eulerian path problem. The paper focuses on global multiple alignment of DNA sequences, where entire sequences are aligned into one configuration. Our main result is an algorithm with almost linear computational speed with respect to the total size (number of letters) of sequences to be aligned. Five hundred simulated sequences (averaging 500 bases per sequence and as low as 70% pairwise identity) have been aligned within three minutes on a personal computer, and the quality of alignment is satisfactory. As a result, accurate and simultaneous alignment of thousands of long sequences within a reasonable amount of time becomes possible. Data from an Arabidopsis sequencing project is used to demonstrate the performance.
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.
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.
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.
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.
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
122115079
An Iterative Method for the Inversion of the Two-Dimensional Wave Equation with a Potential
A numerical method for a nonlinear inversion problem for the 2D wave equation with a potential is discussed. In order to avoid the ill-posedness, we substitute a coupled system of one-way wave equations for the original wave equation. An iterative algorithm is constructed to improve the accuracy of the inversion. Numerical experiments are performed on several examples to examine the effectiveness of this method.
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.
4002740
Selectivity Estimation by Batch-Query based Histogram and Parametric Method
Histograms are used extensively for selectivity estimation and approximate query processing. Workload-aware dynamic histograms can self-tune itself based on query feedback without scanning or sampling the underlaying datasets in a systematic and comprehensive way. Dynamic histograms allocate more buckets not only for the areas with most skewed data distribution but also according to users' interest. However, it takes long time to 'warm-up' (i.e., a large number of queries need to be processed before the histogram can provide a satisfactory coverage and accuracy). Thus, it is less effective to adapt with workload pattern changes. In this paper, we propose a novel online query scheduling algorithm which can significantly reduce the warm-up time for dynamic histograms. A parametric method is proposed to remedy the problem of inaccurate query selectivity estimation for the areas with poor histogram coverage. Experimental results demonstrate a significant effectiveness and accuracy improvement of our approach.
9462041
HPtaa database-potential target genes for clinical diagnosis and immunotherapy of human carcinoma
Tumor-associated antigens (TAAs) have been the most actively employed targets in the clinical diagnosis and treatment of human carcinoma, such as PSA in the diagnosis of prostate cancer and NY-ESO-1 in the immunotherapy of melanoma and other cancers. However, identification of TAAs has often been hampered by the complicated and laborsome laboratory procedures. In order to accelerate the process of tumor antigen discovery, and thereby improve diagnosis and treatment of human carcinoma, we have made an effort to establish a publicly available Human Potential Tumor Associated Antigen database (HPtaa) with potential TAAs identified by in silico computing (http://www.hptaa.org). Tumor specificity was chosen as the core of tumor antigen evaluation, together with other relevant clues. Various platforms of gene expression, including microarray, expressed sequence tag and SAGE data, were processed and integrated by several penalty algorithms. A total of 3518 potential TAAs have been included in the database, which is freely available to academic users. As far as we know, this database is the first one addressing human potential TAAs, and the first one integrating various kinds of expression platforms for one purpose.
4846997
Semi-supervised Discriminant Analysis Via CCCP
Linear discriminant analysis (LDA) is commonly used for dimensionality reduction. In real-world applications where labeled data are scarce, LDA does not work very well. However, unlabeled data are often available in large quantities. We propose a novel semi-supervised discriminant analysis algorithm called SSDA$_{\mathit{CCCP}}$. We utilize unlabeled data to maximize an optimality criterion of LDA and use the constrained concave-convex procedure to solve the optimization problem. The optimization procedure leads to estimation of the class labels for the unlabeled data. We propose a novel confidence measure for selecting those unlabeled data points with high confidence. The selected unlabeled data can then be used to augment the original labeled data set for performing LDA. We also propose a variant of SSDA$_{\mathit{CCCP}}$, called M-SSDA$_{\mathit{CCCP}}$, which adopts the manifold assumption to utilize the unlabeled data. Extensive experiments on many benchmark data sets demonstrate the effectiveness of our proposed methods.