Copy number variations (CNVs) are an important class of variations contributing to the pathogenesis of many disease phenotypes. Detecting CNVs from genomic data remains difficult, and the most currently applied methods suffer from an unacceptably high false positive rate. A common practice is to have human experts manually review original CNV calls for filtering false positives before further downstream analysis or experimental validation. Here, we propose DeepCNV, a deep learning-based tool, intended to replace human experts when validating CNV calls, focusing on the calls made by one of the most accurate CNV callers, PennCNV. The sophistication of the deep neural network algorithm is enriched with over 10 000 expert-scored samples that are split into training and testing sets. Variant confidence, especially for CNVs, is a main roadblock impeding the progress of linking CNVs with the disease. We show that DeepCNV adds to the confidence of the CNV calls with an optimal area under the receiver operating characteristic curve of 0.909, exceeding other machine learning methods. The superiority of DeepCNV was also benchmarked and confirmed using an experimental wet-lab validation dataset. We conclude that the improvement obtained by DeepCNV results in significantly fewer false positive results and failures to replicate the CNV association results.

With the development of high throughput technology, it has become feasible and common to profile tens of thousands of gene activities simultaneously. These genomic data typically have sample size of hundreds or fewer, which is much less than the feature size (number of genes). In addition, the genes, in particular the ones from the same pathway, are often highly correlated. These issues impose a great challenge for selecting meaningful genes from a large number of (correlated) candidates in many genomic studies. Quite a few methods have been proposed to attack this challenge. Among them, regularization-based techniques, e.g., lasso, become much more appealing, because they can do model fitting and variable selection at the same time. However, the lasso regression has its known limitations. One is that the number of genes selected by the lasso couldn't exceed the number of samples. Another limitation is that, if causal genes are highly correlated, the lasso tends to select only one or few genes from them. Biologists, however, desire to identify them all. To overcome these limitations, we present here a novel, robust, and stable variable selection method. Through simulation studies and a real application to the transcriptome data, we demonstrate the superiority of the proposed method in selecting highly correlated causal genes. We also provide some theoretical justifications for this feature sampling strategy based on the mean and variance analyses.

Online peer-to-peer (P2P) lending is expected to benefit both investors and borrowers due to their low transaction cost and the elimination of expensive intermediaries. From the lenders' perspective, maximizing their return on investment is an ultimate goal during their decision-making procedure. In this paper, we explore and address a fundamental problem underlying such a goal: how to represent the two competing risks, charge-off and prepayment, in funded loans. We propose to model both potential risks simultaneously, which remains largely unexplored until now. We first develop a hierarchical grading framework to integrate two risks of loans both qualitatively and quantitatively. Afterward, we introduce an end-to-end deep learning approach to solve this problem by breaking it down into multiple binary classification subproblems that are amenable to both feature representation and risks learning. Particularly, we leverage deep neural networks to jointly solve these subtasks, which leads to the in-depth exploration of the interaction involved in these tasks. To the best of our knowledge, this is the first attempt to characterize competing risks for loans in P2P lending via deep neural networks. The comprehensive experiments on real-world loan data show that our methodology is able to achieve an appealing investment performance by modeling the competition within and between risks explicitly and properly. The feature analysis based on saliency maps provides useful insights into payment dynamics of loans for potential investors intuitively.

Online advertising delivers promotional marketing messages to consumers through online media. Advertisers often have the desire to optimize their advertising spending strategies in order to gain the highest return on investment and maximize their key performance indicator. To build accurate advertisement performance predictive models, it is crucial to detect the change-points in the historical data and apply appropriate strategies to address a data pattern shift problem. However, with sparse data, which is common in online advertising and some other applications, online change-point detection is very challenging. We present a novel collaborated online change-point detection method in this paper. Through efficiently leveraging and coordinating with auxiliary time series, we can quickly and accurately identify the change-points in sparse and noisy time series. Simulation studies as well as real data experiments have justified the proposed method's effectiveness in detecting change-points in sparse time series. Therefore, it can be used to improve the accuracy of predictive models.

Motivation: Recent studies have revealed a complex interplay between environment, the human microbiome and health and disease. Mediation analysis of the human microbiome in these complex relationships could potentially provide insights into the role of the microbiome in the etiology of disease and, more importantly, lead to novel clinical interventions by modulating the microbiome. However, due to the high dimensionality, sparsity, non-normality and phylogenetic structure of microbiome data, none of the existing methods are suitable for testing such clinically important mediation effect. Results: We propose a distance-based approach for testing the mediation effect of the human microbiome. In the framework, the nonlinear relationship between the human microbiome and independent/dependent variables is captured implicitly through the use of sample-wise ecological distances, and the phylogenetic tree information is conveniently incorporated by using phylogeny-based distance metrics. Multiple distance metrics are utilized to maximize the power to detect various types of mediation effect. Simulation studies demonstrate that our method has correct Type I error control, and is robust and powerful under various mediation models. Application to a real gut microbiome dataset revealed that the association between the dietary fiber intake and body mass index was mediated by the gut microbiome. Availability and implementation: An R package 'MedTest' is freely available at https://github.com/jchen1981/MedTest. Contact: [email protected] or [email protected]. Supplementary information: Supplementary data are available at Bioinformatics online.

With the growth of the digital advertising market, it has become more important than ever to target the desired audiences. Among various demographic traits, gender information plays a key role in precisely targeting the potential consumers in online advertising and ecommerce. However, such personal information is generally unavailable to digital media sellers. In this paper, we propose a novel task-specific multi-task learning algorithm to predict users' gender information from their video viewing behaviors. To detect as many desired users as possible, while controlling the Type I error rate at a user-specified level, we further propose Bayes testing and decision procedures to efficiently identify male and female users, respectively. Comprehensive experiments have justified the effectiveness and reliability of our framework.

MOTIVATION: Next-generation RNA sequencing (RNA-seq) has been widely used to investigate alternative isoform regulations. Among them, alternative 3 ': splice site (SS) and 5 ': SS account for more than 30% of all alternative splicing (AS) events in higher eukaryotes. Recent studies have revealed that they play important roles in building complex organisms and have a critical impact on biological functions which could cause disease. Quite a few analytical methods have been developed to facilitate alternative 3 ': SS and 5 ': SS studies using RNA-seq data. However, these methods have various limitations and their performances may be further improved. RESULTS: We propose an empirical Bayes change-point model to identify alternative 3 ': SS and 5 ': SS. Compared with previous methods, our approach has several unique merits. First of all, our model does not rely on annotation information. Instead, it provides for the first time a systematic framework to integrate various information when available, in particular the useful junction read information, in order to obtain better performance. Second, we utilize an empirical Bayes model to efficiently pool information across genes to improve detection efficiency. Third, we provide a flexible testing framework in which the user can choose to address different levels of questions, namely, whether alternative 3 ': SS or 5 ': SS happens, and/or where it happens. Simulation studies and real data application have demonstrated that our method is powerful and accurate. AVAILABILITY AND IMPLEMENTATION: The software is implemented in Java and can be freely downloaded from http://ebchangepoint.sourceforge.net/ CONTACT: [email protected].

Online advertising delivers promotional marketing messages to consumers through online media. Advertisers often have the desire to optimize their advertising spending and strategies in order to maximize their KPI (Key performance indicator). To build accurate ad performance predictive models, it is crucial to detect the change-points in historical data and therefore apply appropriate strategies to address the data pattern shift. However, with sparse data, which is common in online advertising, online change-point detection often becomes challenging. We propose a novel collaborated online change-point detection method in this paper. Through efficiently leveraging and coordinating with auxiliary time series, it can quickly and accurately identify the change-points in sparse and noisy time series. Simulation studies as well as real data applications have demonstrated its effectiveness in detecting change-point in sparse time series and therefore improving the accuracy of predictive models.