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For larger proteins, and proteins not amenable to expression in bacterial hosts, it is difficult to deduce structures using NMR methods based on uniform 13C, 15N isotopic labeling and observation of just nuclear Overhauser effects (NOEs). In these cases, sparse labeling with selected 15N enriched amino acids and extraction of a wider variety of backbone-centered structural constraints is providing an alternate approach. A limitation, however, is the absence of resonance assignment strategies that work without uniform 15N, 13C labeling or preparation of numerous samples labeled with pairs of isotopically labeled amino acids. In this paper an approach applicable to a single sample prepared with sparse 15N labeling in selected amino acids is presented. It relies on correlation of amide proton exchange rates, measured from data on the intact protein and on digested and sequenced peptides. Application is illustrated using the carbohydrate binding protein, Galectin-3. Limitations and future applications are discussed.  相似文献   
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The relative risk (RR) is one of the most frequently used indices to measure the strength of association between a disease and a risk factor in etiological studies or the efficacy of an experimental treatment in clinical trials. In this paper, we concentrate attention on interval estimation of RR for sparse data, in which we have only a few patients per stratum, but a moderate or large number of strata. We consider five asymptotic interval estimators for RR, including a weighted least-squares (WLS) interval estimator with an ad hoc adjustment procedure for sparse data, an interval estimator proposed elsewhere for rare events, an interval estimator based on the Mantel-Haenszel (MH) estimator with a logarithmic transformation, an interval estimator calculated from a quadratic equation, and an interval estimator derived from the ratio estimator with a logarithmic transformation. On the basis of Monte Carlo simulations, we evaluate and compare the performance of these five interval estimators in a variety of situations. We note that, except for the cases in which the underlying common RR across strata is around 1, using the WLS interval estimator with the adjustment procedure for sparse data can be misleading. We note further that using the interval estimator suggested elsewhere for rare events tends to be conservative and hence leads to loss of efficiency. We find that the other three interval estimators can consistently perform well even when the mean number of patients for a given treatment is approximately 3 patients per stratum and the number of strata is as small as 20. Finally, we use a mortality data set comparing two chemotherapy treatments in patients with multiple myeloma to illustrate the use of the estimators discussed in this paper.  相似文献   
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The estimation of the unknown parameters in the stratified Cox's proportional hazard model is a typical example of the trade‐off between bias and precision. The stratified partial likelihood estimator is unbiased when the number of strata is large but suffer from being unstable when many strata are non‐informative about the unknown parameters. The estimator obtained by ignoring the heterogeneity among strata, on the other hand, increases the precision of estimates although pays the price for being biased. An estimating procedure, based on the asymptotic properties of the above two estimators, serving to compromise between bias and precision is proposed. Two examples in a radiosurgery for brain metastases study provide some interesting demonstration of such applications.  相似文献   
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In cancer classification, gene selection is an important data preprocessing technique, but it is a difficult task due to the large search space. Accordingly, the objective of this study is to develop a hybrid meta-heuristic Binary Black Hole Algorithm (BBHA) and Binary Particle Swarm Optimization (BPSO) (4-2) model that emphasizes gene selection. In this model, the BBHA is embedded in the BPSO (4-2) algorithm to make the BPSO (4-2) more effective and to facilitate the exploration and exploitation of the BPSO (4-2) algorithm to further improve the performance. This model has been associated with Random Forest Recursive Feature Elimination (RF-RFE) pre-filtering technique. The classifiers which are evaluated in the proposed framework are Sparse Partial Least Squares Discriminant Analysis (SPLSDA); k-nearest neighbor and Naive Bayes. The performance of the proposed method was evaluated on two benchmark and three clinical microarrays. The experimental results and statistical analysis confirm the better performance of the BPSO (4-2)-BBHA compared with the BBHA, the BPSO (4-2) and several state-of-the-art methods in terms of avoiding local minima, convergence rate, accuracy and number of selected genes. The results also show that the BPSO (4-2)-BBHA model can successfully identify known biologically and statistically significant genes from the clinical datasets.  相似文献   
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The accelerating growth of the public microbial genomic data imposes substantial burden on the research community that uses such resources.Building databases for non-redundant reference sequences from massive microbial genomic data based on clustering analysis is essential.However,existing clustering algorithms perform poorly on long genomic sequences.In this article,we present Gclust,a parallel program for clustering complete or draft genomic sequences,where clustering is accelerated with a novel parallelization strategy and a fast sequence comparison algorithm using sparse suffix arrays(SSAs).Moreover,genome identity measures between two sequences are calculated based on their maximal exact matches(MEMs).In this paper,we demonstrate the high speed and clustering quality of Gclust by examining four genome sequence datasets.Gclust is freely available for non-commercial use at https://github.com/niu-lab/gclust.We also introduce a web server for clustering user-uploaded genomes at http://niulab.scgrid.cn/gclust.  相似文献   
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