A fast algorithm for detecting gene-gene interactions in genome-wide association studies

With the recent advent of high-throughput genotyping techniques, genetic data for genome-wide association studies (GWAS) have become increasingly available, which entails the development of efficient and effective statistical approaches. Although many such approaches have been developed and used to identify single-nucleotide polymorphisms (SNPs) that are associated with complex traits or diseases, few are able to detect gene-gene interactions among different SNPs. Genetic interactions, also known as epistasis, have been recognized to play a pivotal role in contributing to the genetic variation of phenotypic traits. However, because of an extremely large number of SNP-SNP combinations in GWAS, the model dimensionality can quickly become so overwhelming that no prevailing variable selection methods are capable of handling this problem. In this paper, we present a statistical framework for characterizing main genetic effects and epistatic interactions in a GWAS study. Specifically, we first propose a two-stage sure independence screening (TS-SIS) procedure and generate a pool of candidate SNPs and interactions, which serve as predictors to explain and predict the phenotypes of a complex trait. We also propose a rates adjusted thresholding estimation (RATE) approach to determine the size of the reduced model selected by an independence screening. Regularization regression methods, such as LASSO or SCAD, are then applied to further identify important genetic effects. Simulation studies show that the TS-SIS procedure is computationally efficient and has an outstanding finite sample performance in selecting potential SNPs as well as gene-gene interactions. We apply the proposed framework to analyze an ultrahigh-dimensional GWAS data set from the Framingham Heart Study, and select 23 active SNPs and 24 active epistatic interactions for the body mass index variation. It shows the capability of our procedure to resolve the complexity of genetic control.Comment: Published in at http://dx.doi.org/10.1214/14-AOAS771 the Annals of Applied Statistics (http://www.imstat.org/aoas/) by the Institute of Mathematical Statistics (http://www.imstat.org

Practical Block-wise Neural Network Architecture Generation

Convolutional neural networks have gained a remarkable success in computer vision. However, most usable network architectures are hand-crafted and usually require expertise and elaborate design. In this paper, we provide a block-wise network generation pipeline called BlockQNN which automatically builds high-performance networks using the Q-Learning paradigm with epsilon-greedy exploration strategy. The optimal network block is constructed by the learning agent which is trained sequentially to choose component layers. We stack the block to construct the whole auto-generated network. To accelerate the generation process, we also propose a distributed asynchronous framework and an early stop strategy. The block-wise generation brings unique advantages: (1) it performs competitive results in comparison to the hand-crafted state-of-the-art networks on image classification, additionally, the best network generated by BlockQNN achieves 3.54% top-1 error rate on CIFAR-10 which beats all existing auto-generate networks. (2) in the meanwhile, it offers tremendous reduction of the search space in designing networks which only spends 3 days with 32 GPUs, and (3) moreover, it has strong generalizability that the network built on CIFAR also performs well on a larger-scale ImageNet dataset.Comment: Accepted to CVPR 201