We consider a wireless network scenario applicable to metropolitan areas with developed public transport networks and high commute demands, where the mobile user equipments (UEs) move along fixed and predetermined trajectories and request to associate with millimeter-wave (mmWave) base stations (BSs). An effective and efficient algorithm, called the Sequence Q-learning Algorithm (SQA), is proposed to maximize the long-run average transmission rate of the network, which is an NP-hard problem. Furthermore, the SQA tackles the complexity issue by only allowing possible re-associations (handover of a UE from one BS to another) at a discrete set of decision epochs and has polynomial time complexity. This feature of the SQA also restricts too frequent handovers, which are considered highly undesirable in mmWave networks. Moreover, we demonstrate by extensive numerical results that the SQA can significantly outperform the benchmark algorithms proposed in existing research by taking all UEs’ future trajectories and possible decisions into account at every decision epoch.

Single-cell RNA-Sequencing (scRNA-Seq), an advanced sequencing technique, enables biomedical researchers to characterize cell-specific gene expression profiles. Although studies have adapted machine learning algorithms to cluster different cell populations for scRNA-Seq data, few existing methods have utilized machine learning techniques to investigate functional pathways in classifying heterogeneous cell populations. As genes often work interactively at the pathway level, studying the cellular heterogeneity based on pathways can facilitate the interpretation of biological functions of different cell populations. In this paper, we propose a pathway-based analytic framework using Random Forests (RF) to identify discriminative functional pathways related to cellular heterogeneity as well as to cluster cell populations for scRNA-Seq data. We further propose a novel method to construct gene-gene interactions (GGIs) networks using RF that illustrates important GGIs in differentiating cell populations. The co-occurrence of genes in different discriminative pathways and 'cross-talk' genes connecting those pathways are also illustrated in our networks. Our novel pathway-based framework clusters cell populations, prioritizes important pathways, highlights GGIs and pivotal genes bridging cross-talked pathways, and groups co-functional genes in networks. These features allow biomedical researchers to better understand the functional heterogeneity of different cell populations and to pinpoint important genes driving heterogeneous cellular functions.

BACKGROUND: High-throughput techniques bring novel tools and also statistical challenges to genomic research. Identifying genes with differential expression between different species is an effective way to discover evolutionarily conserved transcriptional responses. To remove systematic variation between different species for a fair comparison, normalization serves as a crucial pre-processing step that adjusts for the varying sample sequencing depths and other confounding technical effects. RESULTS: In this paper, we propose a scale based normalization (SCBN) method by taking into account the available knowledge of conserved orthologous genes and by using the hypothesis testing framework. Considering the different gene lengths and unmapped genes between different species, we formulate the problem from the perspective of hypothesis testing and search for the optimal scaling factor that minimizes the deviation between the empirical and nominal type I errors. CONCLUSIONS: Simulation studies show that the proposed method performs significantly better than the existing competitor in a wide range of settings. An RNA-seq dataset of different species is also analyzed and it coincides with the conclusion that the proposed method outperforms the existing method. For practical applications, we have also developed an R package named "SCBN", which is freely available at http://www.bioconductor.org/packages/devel/bioc/html/SCBN.html .

In nonparametric regression, the derivative estimation has attracted much attention in recent years due to its wide applications. In this paper, we propose a new method for the derivative estimation using the locally weighted least absolute deviation regression. Different from the local polynomial regression, the proposed method does not require a finite variance for the error term and so is robust to the presence of heavy-tailed errors. Meanwhile, it does not require a zero median or a positive density at zero for the error term in comparison with the local median regression. We further show that the proposed estimator with random difference is asymptotically equivalent to the (infinitely) composite quantile regression estimator. In other words, running one regression is equivalent to combining infinitely many quantile regressions. In addition, the proposed method is also extended to estimate the derivatives at the boundaries and to estimate higher-order derivatives. For the equidistant design, we derive theoretical results for the proposed estimators, including the asymptotic bias and variance, consistency, and asymptotic normality. Finally, we conduct simulation studies to demonstrate that the proposed method has better performance than the existing methods in the presence of outliers and heavy-tailed errors, and analyze the Chinese house price data for the past ten years to illustrate the usefulness of the proposed method.

Motivation: With the development of high-throughput techniques, RNA-sequencing (RNA-seq) is becoming increasingly popular as an alternative for gene expression analysis, such as RNAs profiling and classification. Identifying which type of diseases a new patient belongs to with RNA-seq data has been recognized as a vital problem in medical research. As RNA-seq data are discrete, statistical methods developed for classifying microarray data cannot be readily applied for RNA-seq data classification. Witten proposed a Poisson linear discriminant analysis (PLDA) to classify the RNA-seq data in 2011. Note, however, that the count datasets are frequently characterized by excess zeros in real RNA-seq or microRNA sequence data (i.e. when the sequence depth is not enough or small RNAs with the length of 18-30 nucleotides). Therefore, it is desired to develop a new model to analyze RNA-seq data with an excess of zeros. Results: In this paper, we propose a Zero-Inflated Poisson Logistic Discriminant Analysis (ZIPLDA) for RNA-seq data with an excess of zeros. The new method assumes that the data are from a mixture of two distributions: one is a point mass at zero, and the other follows a Poisson distribution. We then consider a logistic relation between the probability of observing zeros and the mean of the genes and the sequencing depth in the model. Simulation studies show that the proposed method performs better than, or at least as well as, the existing methods in a wide range of settings. Two real datasets including a breast cancer RNA-seq dataset and a microRNA-seq dataset are also analyzed, and they coincide with the simulation results that our proposed method outperforms the existing competitors. Availability and implementation: The software is available at http://www.math.hkbu.edu.hk/∼tongt. Contact: [email protected] or [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

BACKGROUND: RNA-sequencing (RNA-Seq) has become a powerful technology to characterize gene expression profiles because it is more accurate and comprehensive than microarrays. Although statistical methods that have been developed for microarray data can be applied to RNA-Seq data, they are not ideal due to the discrete nature of RNA-Seq data. The Poisson distribution and negative binomial distribution are commonly used to model count data. Recently, Witten (Annals Appl Stat 5:2493-2518, 2011) proposed a Poisson linear discriminant analysis for RNA-Seq data. The Poisson assumption may not be as appropriate as the negative binomial distribution when biological replicates are available and in the presence of overdispersion (i.e., when the variance is larger than or equal to the mean). However, it is more complicated to model negative binomial variables because they involve a dispersion parameter that needs to be estimated. RESULTS: In this paper, we propose a negative binomial linear discriminant analysis for RNA-Seq data. By Bayes' rule, we construct the classifier by fitting a negative binomial model, and propose some plug-in rules to estimate the unknown parameters in the classifier. The relationship between the negative binomial classifier and the Poisson classifier is explored, with a numerical investigation of the impact of dispersion on the discriminant score. Simulation results show the superiority of our proposed method. We also analyze two real RNA-Seq data sets to demonstrate the advantages of our method in real-world applications. CONCLUSIONS: We have developed a new classifier using the negative binomial model for RNA-seq data classification. Our simulation results show that our proposed classifier has a better performance than existing works. The proposed classifier can serve as an effective tool for classifying RNA-seq data. Based on the comparison results, we have provided some guidelines for scientists to decide which method should be used in the discriminant analysis of RNA-Seq data. R code is available at http://www.comp.hkbu.edu.hk/~xwan/NBLDA.R or https://github.com/yangchadam/NBLDA.

We propose a simple framework for estimating derivatives without fitting the regression function in nonparametric regression. Unlike most existing methods that use the symmetric difference quotients, our method is constructed as a linear combination of observations. It is hence very flexible and applicable to both interior and boundary points, including most existing methods as special cases of ours. Within this framework, we define the variance-minimizing estimators for any order derivative of the regression function with a fixed bias-reduction level. For the equidistant design, we derive the asymptotic variance and bias of these estimators. We also show that our new method will, for the first time, achieve the asymptotically optimal convergence rate for difference-based estimators. Finally, we provide an effective criterion for selection of tuning parameters and demonstrate the usefulness of the proposed method through extensive simulation studies of the first- and second-order derivative estimators.

MOTIVATION: High-dimensional data such as microarrays have created new challenges to traditional statistical methods. One such example is on class prediction with high-dimension, low-sample size data. Due to the small sample size, the sample mean estimates are usually unreliable. As a consequence, the performance of the class prediction methods using the sample mean may also be unsatisfactory. To obtain more accurate estimation of parameters some statistical methods, such as regularizations through shrinkage, are often desired. RESULTS: In this article, we investigate the family of shrinkage estimators for the mean value under the quadratic loss function. The optimal shrinkage parameter is proposed under the scenario when the sample size is fixed and the dimension is large. We then construct a shrinkage-based diagonal discriminant rule by replacing the sample mean by the proposed shrinkage mean. Finally, we demonstrate via simulation studies and real data analysis that the proposed shrinkage-based rule outperforms its original competitor in a wide range of settings.

Although many feature selection methods for classification have been developed, there is a need to identify genes in high-dimensional data with censored survival outcomes. Traditional methods for gene selection in classification problems have several drawbacks. First, the majority of the gene selection approaches for classification are single-gene based. Second, many of the gene selection procedures are not embedded within the algorithm itself. The technique of random forests has been found to perform well in high-dimensional data settings with survival outcomes. It also has an embedded feature to identify variables of importance. Therefore, it is an ideal candidate for gene selection in high-dimensional data with survival outcomes. In this paper, we develop a novel method based on the random forests to identify a set of prognostic genes. We compare our method with several machine learning methods and various node split criteria using several real data sets. Our method performed well in both simulations and real data analysis.Additionally, we have shown the advantages of our approach over single-gene-based approaches. Our method incorporates multivariate correlations in microarray data for survival outcomes. The described method allows us to better utilize the information available from microarray data with survival outcomes.

MOTIVATION: Multiple comparison adjustment is a significant and challenging statistical issue in large-scale biological studies. In previous studies, dependence among genes is largely ignored. However, such dependence may be strong for some genomic-scale studies such as genetical genomics [also called expression quantitative trait loci (eQTL) mapping] in which thousands of genes are treated as quantitative traits and mapped to different genetical markers. Besides the dependence among markers, the dependence among the expression levels of genes can also have a significant impact on data analysis and interpretation. RESULTS: In this article, we propose to consider both the mean as well as the variance of false discovery number for multiple comparison adjustment to handle dependence among hypotheses. This is achieved by developing a variance estimator for false discovery number, and using the upper bound of false discovery proportion (uFDP) for false discovery control. More importantly, we introduce a weighted version of uFDP (wuFDP) control to improve the statistical power of eQTL identification. In addition, the wuFDP approach can better control false positives than false discovery rate (FDR) and uFDP approaches when markers are in linkage disequilibrium. The relative performance of uFDP control and wuFDP control is illustrated through simulation studies and real data analysis. SUPPLEMENTARY INFORMATION: Supplementary figures, tables and appendices are available at Bioinformatics online.