On Spectral Graph Embedding: A Non-Backtracking Perspective and Graph Approximation

Graph embedding has been proven to be efficient and effective in facilitating graph analysis. In this paper, we present a novel spectral framework called NOn-Backtracking Embedding (NOBE), which offers a new perspective that organizes graph data at a deep level by tracking the flow traversing on the edges with backtracking prohibited. Further, by analyzing the non-backtracking process, a technique called graph approximation is devised, which provides a channel to transform the spectral decomposition on an edge-to-edge matrix to that on a node-to-node matrix. Theoretical guarantees are provided by bounding the difference between the corresponding eigenvalues of the original graph and its graph approximation. Extensive experiments conducted on various real-world networks demonstrate the efficacy of our methods on both macroscopic and microscopic levels, including clustering and structural hole spanner detection.Comment: SDM 2018 (Full version including all proofs

Improved Statistical Analysis for Array CGH-Based DNA Copy Number Aberrations

Array-based comparative genomic hybridization (aCGH) allows measuring DNA copy number at the whole genome scale. In cancer studies, one may be interested in identifying DNA copy number aberrations (CNAs) associated with certain clinicopathological characteristics such as cancer metastasis. We proposed to define test regions based on copy number pattern profiles across multiple samples, using either smoothed log2-ratio or discrete data of copy number gain/loss calls. Association test performed on the refined test regions instead of the probes has improved power due to reduced number of tests. We also compared three types of measurement of copy number levels, normalized log2-ratio, smoothed log2-ratio, and copy number gain or loss calls in statistical hypothesis testing. The relative strengths and weaknesses of the proposed method were demonstrated using both simulation studies and real data analysis of a liver cancer study

HIMA2: High-dimensional mediation analysis and its application in epigenome-wide DNA methylation data

Mediation analysis plays a major role in identifying significant mediators in the pathway between environmental exposures and health outcomes. With advanced data collection technology for large-scale studies, there has been growing research interest in developing methodology for high-dimensional mediation analysis. In this paper we present HIMA2, an extension of the HIMA method (Zhang in Bioinformatics 32:3150-3154, 2016). First, the proposed HIMA2 reduces the dimension of mediators to a manageable level based on the sure independence screening (SIS) method (Fan in J R Stat Soc Ser B 70:849-911, 2008). Second, a de-biased Lasso procedure is implemented for estimating regression parameters. Third, we use a multiple-testing procedure to accurately control the false discovery rate (FDR) when testing high-dimensional mediation hypotheses. We demonstrate its practical performance using Monte Carlo simulation studies and apply our method to identify DNA methylation markers which mediate the pathway from smoking to reduced lung function in the Coronary Artery Risk Development in Young Adults (CARDIA) Study

OR-009 The expression and roles of lncRNAs in the regeneration of skeletal muscle contusion

Objective In recent years, Accumulating evidence from myoblast differentiation in vitro, cardiotoxin (CTX)-mediated injury or mdx mice suggested that some lncRNAs such as Malat1, H19, linc-MD1, linc-YY1, Sirt1 AS and lnc-mg may modulate myogenesis and muscle regeneration. However, the change of lncRNAs in skeletal muscle contusion and their possible roles are still unclear. We hypothesize that the lncRNAs may be involved in the repair of skeletal muscle contusion. Methods Forty C57BL/6 male mice were randomly divided into two groups, uninjured control group (group C) and muscle contusion group (group S). The mice of group S suffered from contusion injury. All the mice were killed to harvest gastrocnemius at 3, 6, 12 and 24 days post-injury. The gene expression were detected by PCR technique. Gastrocnemius were stained with H & E to evaluate the general morphology. Data were analyzed by One-way analysis of variance, with statistical significance being set at p ≤ 0.05. Results The expression levels of linc-MD1 and Sirt1 AS were significantly higher than that of the uninjured control group at 3, 6 and 12 days post-injury (p<0.01). And Malat1 was highly expressed in the skeletal muscle of the muscle contusion group at 3 days post-injury and continuously up-regulated at 6 days (p<0.01). Moreover, linc-YY1 and H19 were all elevated significantly at 6 days (all p<0.01), but their gene expression levels did not change significantly at 3, 12 and 24 days post-injury, as compared to the uninjured control group. Furthermore, lnc-mg mRNA level did not change significantly in the whole process of regeneration after muscle contusion except the time point of 12 days post-injury which decreased significantly (p<0.01). The expression of myogenic regulatory factors (MyoD, myogenin, myf5, myf6) were studied, they were all elevated significantly at 3 and 6 days (all p<0.01; except myogenin ), and returned to normal at 24 days post-injury, as compared to the uninjured control group. Meanwhile, Pearson correlations showed that there was an correlation between lincRNAs and myogenic regulatory factors mentioned above. Conclusions The expression of myogenic regulatory factors increased significantly after muscle contusion. Meanwhile, varieties of lncRNAs (Malat1, H19, lnc-mg, linc-MD1, linc-YY1, Sirt1 AS) were also up-regulated. Moreover, there was correlation between lncRNAs and myogenic regulatory factors for skeletal muscle regeneration. These results suggest that lncRNAs may play important roles in the regeneration of skeletal muscle contusion

Evidence for association between Disrupted-in-schizophrenia 1 (DISC1) gene polymorphisms and autism in Chinese Han population: a family-based association study

<p>Abstract</p> <p>Background</p> <p>Disrupted-in-Schizophrenia 1 (<it>DISC1</it>) gene is one of the most promising candidate genes for major mental disorders. In a previous study, a Finnish group demonstrated that <it>DISC1 </it>polymorphisms were associated with autism and Asperger syndrome. However, the results were not replicated in Korean population. To determine whether <it>DISC1 </it>is associated with autism in Chinese Han population, we performed a family-based association study between <it>DISC1 </it>polymorphisms and autism.</p> <p>Methods</p> <p>We genotyped seven tag single nucleotide polymorphisms (SNPs) in <it>DISC1</it>, spanning 338 kb, in 367 autism trios (singleton and their biological parents) including 1,101 individuals. Single SNP association and haplotype association analysis were performed using the family-based association test (FBAT) and Haploview software.</p> <p>Results</p> <p>We found three SNPs showed significant associations with autism (rs4366301: G > C, Z = 2.872, <it>p </it>= 0.004; rs11585959: T > C, Z = 2.199, <it>p </it>= 0.028; rs6668845: A > G, Z = 2.326, <it>p </it>= 0.02). After the Bonferroni correction, SNP rs4366301, which located in the first intron of <it>DISC1</it>, remained significant. When haplotype were constructed with two-markers, three haplotypes displayed significant association with autism. These results were still significant after using the permutation method to obtain empirical <it>p </it>values.</p> <p>Conclusions</p> <p>Our study provided evidence that the <it>DISC1 </it>may be the susceptibility gene of autism. It suggested <it>DISC1 </it>might play a role in the pathogenesis of autism.</p