Gene and Pathway-Based Analysis: Second Wave of Genome-wide Association Studies

Despite great success of GWAS in identification of common genetic variants associated with complex diseases, the current GWAS have focused on single SNP analysis. However, single SNP analysis often identifies a number of the most significant SNPs that account for only a small proportion of the genetic variants and offers limited understanding of complex diseases. To overcome these limitations, we propose gene and pathway-based association analysis as a new paradigm for GWAS. As a proof of concept, we performed a comprehensive gene and pathway-based association analysis for thirteen published GWAS. Our results showed that the proposed new paradigm for GWAS not only identified the genes that include significant SNPs found by single SNP analysis, but also detected new genes in which each single SNP conferred small disease risk, but their joint actions were implicated in the development of diseases. The results also demonstrated that the new paradigm for GWAS was able to identify biologically meaningful pathways associated with the diseases which were confirmed by gene-set rich analysis using gene expression data

Progressive failure analysis of soil slopes considering the influences of humidity and loading

To analyze the progressive failure of structural loess slopes due to changes in humidity and loading, this study analyzes the degrees of influence of these changes on slope failure and their relationships with various structural parameters. According to the analysis, the shear failure of the soil gradually develops with the change of the water content. When the water content reaches a 17%, with the development of shear deformation, the shear zone is formed and finally penetrates the soil body. With the increase of the water content, the total displacement of the slope body gradually develops. When the water content reaches 17%, the total displacement of the slope body changes suddenly. This mutation is consistent with the formation of the shear zone. The sudden change of displacement indicates the penetration of the shear zone and the damage and slippage of the slope. With the increase of the soil moisture of the slope, the strain localization phenomenon occurs, the development of strain localization and shear bands increases, the structural damage increases, and the quantitative structural parameters decrease. The quantitative parameters can therefore be used to evaluate the feasibility and rationality of the progressive failure process of homogeneous structural loess slopes

Adaptive non-local means for multiview image denoising: Searching for the right patches via a statistical approach

ABSTRACT We present an adaptive non-local means (NLM) denoising method for a sequence of images captured by a multiview imaging system, where direct extensions of existing single image NLM methods are incapable of producing good results. Our proposed method consists of three major components: (1) a robust joint-view distance metric to measure the similarity of patches; (2) an adaptive procedure derived from statistical properties of the estimates to determine the optimal number of patches to be used; (3) a new NLM algorithm to denoise using only a set of similar patches. Experimental results show that the proposed method is robust to disparity estimation error, out-performs existing algorithms in multiview settings, and performs competitively in video settings. Index Terms-Non-local means, adaptive filtering, multiview denoising, patch-based denoisin

The classicality and quantumness of a quantum ensemble

In this paper, we investigate the classicality and quantumness of a quantum ensemble. We define a quantity called classicality to characterize how classical a quantum ensemble is. An ensemble of commuting states that can be manipulated classically has a unit classicality, while a general ensemble has a classicality less than 1. We also study how quantum an ensemble is by defining a related quantity called quantumness. We find that the classicality of an ensemble is closely related to how perfectly the ensemble can be cloned, and that the quantumness of an ensemble is essentially responsible for the security of quantum key distribution(QKD) protocols using that ensemble. Furthermore, we show that the quantumness of an ensemble used in a QKD protocol is exactly the attainable lower bound of the error rate in the sifted key.Comment: 5 pages, 1 figur

Variations in the fecal microbiota and their functions of Thoroughbred, Mongolian, and Hybrid horses

The horse gut is colonized by a rich and complex microbial community that has important roles in horse physiology, metabolism, nutrition, and immune functions. Fewer across-breed variations in horse gut microbial diversity have been illustrated. In this article, the gut microbiota of Thoroughbred, Mongolian, and Hybrid horses [first filial generation (F1) of Mongolian (maternal) and Thoroughbred (paternal)] were studied by second-generation high-throughput sequencing technology. Differences in gut microbiota composition and function between breeds were determined using diversity and functional prediction analysis. The alpha diversity analysis showed that Thoroughbred horses had a more abundant and diverse gut microbiota, while the diversity of gut microbiota in Hybrid horses was intermediate between Thoroughbred and Mongolian horses. Subsequent cluster analysis showed that Hybrid horses have a microbiota composition more similar to Mongolian horses. LEfSe analysis revealed that the bacterial biomarkers for Thoroughbred horses at the family level were Prevotellaceae, Rikenellaceae, Fibrobacteraceae, p_251_o5, Lactobacillaceae, and uncultured_bacterium_o_WCHB1_41; the bacterial biomarker for Mongolian horses was Planococcaceae; and the bacterial biomarkers for Hybrid horses were Moraxellaceae, Enterobacteriaceae, and Ruminococcaceae. The functional prediction results indicated that the metabolic pathways differ significantly between the breeds. Regarding metabolism, the Hybrid horses had the lowest proportion of the carbohydrate metabolic pathways, while the energy metabolic pathway had the highest proportion. The abundance ratios of the remaining eight metabolic pathways in Hybrid horses were between Thoroughbred and Mongolian horses. In conclusion, the results of this study showed an association between horse breeds and gut microbiota

Integrated analysis of mutations, miRNA and mRNA expression in glioblastoma

BACKGROUND: Glioblastoma arises from complex interactions between a variety of genetic alterations and environmental perturbations. Little attention has been paid to understanding how genetic variations, altered gene expression and microRNA (miRNA) expression are integrated into networks which act together to alter regulation and finally lead to the emergence of complex phenotypes and glioblastoma. RESULTS: We identified association of somatic mutations in 14 genes with glioblastoma, of which 8 genes are newly identified, and association of loss of heterozygosity (LOH) is identified in 11 genes with glioblastoma, of which 9 genes are newly discovered. By gene coexpression network analysis, we indentified 15 genes essential to the function of the network, most of which are cancer related genes. We also constructed miRNA coexpression networks and found 19 important miRNAs of which 3 were significantly related to glioblastoma patients' survival. We identified 3,953 predicted miRNA-mRNA pairs, of which 14 were previously verified by experiments in other groups. Using pathway enrichment analysis we also found that the genes in the target network of the top 19 important miRNAs were mainly involved in cancer related signaling pathways, synaptic transmission and nervous systems processes. Finally, we developed new methods to decipher the pathway connecting mutations, expression information and glioblastoma. We indentified 4 cis-expression quantitative trait locus (eQTL): TP53, EGFR, NF1 and PIK3C2G; 262 trans eQTL and 26 trans miRNA eQTL for somatic mutation; 2 cis-eQTL: NRAP and EGFR; 409 trans- eQTL and 27 trans- miRNA eQTL for lost of heterozygosity (LOH) mutation. CONCLUSIONS: Our results demonstrate that integrated analysis of multi-dimensional data has the potential to unravel the mechanism of tumor initiation and progression