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Haplotypes have gained increasing attention in the mapping of complex-disease genes, because of the abundance of single-nucleotide polymorphisms (SNPs) and the limited power of conventional single-locus analyses. It has been shown that haplotype-inference methods such as Clark’s algorithm, the expectation-maximization algorithm, and a coalescence-based iterative-sampling algorithm are fairly effective and economical alternatives to molecular-hap-lotyping methods. To contend with some weaknesses of the existing algorithms, we propose a new Monte Carlo approach. In particular, we first partition the whole haplotype into smaller segments. Then, we use the Gibbs sampler both to construct the partial haplotypes of each segment and to assemble all the segments together. Our algorithm can accurately and rapidly infer haplotypes for a large number of linked SNPs. By using a wide variety of real and simulated data sets, we demonstrate the advantages of our Bayesian algorithm, and we show that it is robust to the violation of Hardy-Weinberg equilibrium, to the presence of missing data, and to occurrences of recombination hotspots.

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We present a general boosting method extending functional gradient boosting to optimize complex loss functions that are encountered in many machine learning problems. Our approach is based on optimization of quadratic upper bounds of the loss functions which allows us to present a rigorous convergence analysis of the algorithm. More importantly, this general framework enables us to use a standard regression base learner such as single regression tree for £tting any loss function. We illustrate an application of the proposed method in learning ranking functions for Web search by combining both preference data and labeled data for training. We present experimental results for Web search using data from a commercial search engine that show signi£cant improvements of our proposed methods over some existing methods. 1

Recent studies have revealed that linkage disequilibrium (LD) patterns vary across the human genome with some regions of high LD interspersed by regions of low LD. A small fraction of SNPs (tag SNPs) is sufficient to capture most of the haplotype structure of the human genome. In this paper, we develop a method to partition haplotypes into blocks and to identify tag SNPs based on genotype data by combining a dynamic programming algorithm for haplotype block partitioning and tag SNP selection based on haplotype data with a variation of the expectation maximization (EM) algorithm for haplotype inference. We assess the effects of using either haplotype or genotype data in haplotype block identification and tag SNP selection as a function of several factors, including sample size, density or number of SNPs studied, allele frequencies, fraction of missing data, and genotyping error rate, using extensive simulations. We find that a modest number of haplotype or genotype samples will result in consistent block partitions and tag SNP selection. The power of association studies based on tag SNPs using genotype data is similar to that using haplotype data. Linkage disequilibrium (LD), which refers to the nonrandom as-sociation of alleles at different loci (Lewontin 1964) in haplo-types, plays a central role in genome-wide association studies for identifying genetic variation responsible for common diseases

Recurrent event queries (REQ) constitute a special class of search queries occurring at regular, predictable time intervals. The freshness of documents ranked for such queries is generally of critical importance. REQ forms a significant volume, as much as 6 % of query traffic received by search engines. In this work, we develop an improved REQ classifier that could provide significant improvements in addressing this problem. We analyze REQ queries, and develop novel features from multiple sources, and evaluate them using machine learning techniques. From historical query logs, we develop features utilizing query frequency, click information, and user intent dynamics within a search session. We also develop temporal features by time series analysis from query frequency. Other generated features include word matching with recurrent event seed words and time sensitivity of search result set. We use Naive Bayes, SVM and decision tree based logistic regression model to train REQ classifier. The results on test data show that our models outperformed baseline approach significantly. Experiments on a commercial Web search engine also show significant gains in overall relevance, and thus overall user experience. 1

TRAF2 phosphorylation promotes NF-κB– dependent gene expression and inhibits oxidative stress–induced cell death

Realtime web search refers to the retrieval of very fresh content which is in high demand. An effective portal web search engine must support a variety of search needs, including realtime web search. However, supporting realtime web search introduces two challenges not encountered in non-realtime web search: quickly crawling relevant content and ranking documents with impoverished link and click information. In this paper, we advocate the use of realtime micro-blogging data for addressing both of these problems. We propose a method to use the micro-blogging data stream to detect fresh URLs. We also use micro-blogging data to compute novel and effective features for ranking fresh URLs. We demonstrate these methods improve effective of the portal web search engine for realtime web search.

Effective ranking functions are an essential part of commercial search engines. We focus on developing a regression framework for learning ranking functions for improving relevance of search engines serving diverse streams of user queries. We explore supervised learning methodology from machine learning, and we distinguish two types of relevance judgments used as the training data: 1) absolute relevance judgments arising from explicit labeling of search results; and 2) relative relevance judgments extracted from user clickthroughs of search results or converted from the absolute relevance judgments. We propose a novel optimization framework emphasizing the use of relative relevance judgments. The main contribution is the development of an algorithm based on regression that can be applied to objective functions involving preference data, i.e., data indicating that a document is more relevant than another with respect to a query. Experimental results are carried out using data sets obtained from a commercial search engine. Our results show significant improvements of our proposed methods over some existing methods.

The Shigella bacteria cause bacillary dysentery, 15 which remains a significant threat to public health. The genus status and species classification appear no longer valid, as compelling evidence indicates that Shigella, as well as enteroinvasive Escherichia coli, are derived from multiple origins of E.coli and form a 20 single pathovar. Nevertheless, Shigella dysenteriae serotype 1 causes deadly epidemics but Shigella boydii is restricted to the Indian subcontinent, while Shigella flexneri and Shigella sonnei are prevalent in developing and developed countries respectively. 25 To begin to explain these distinctive epidemiological and pathological features at the genome level, we have carried out comparative genomics on four rep-resentative strains. Each of the Shigella genomes includes a virulence plasmid that encodes conserved 30 primary virulence determinants. The Shigella chro-mosomes share most of their genes with that of E.coli K12 strain MG1655, but each has over 200 pseudogenes, 300700 copies of insertion sequence (IS) elements, and numerous deletions, insertions, 35 translocations and inversions. There is extensive diversity of putative virulence genes, mostly acquired via bacteriophage-mediated lateral gene transfer. Hence, via convergent evolution involving gain and loss of functions, through bacteriophage-mediated 40gene acquisition, IS-mediated DNA rearrangements and formation of pseudogenes, the Shigella spp. became highly specific human pathogens with vari-able epidemiological and pathological features.