Ju Xiang

Multi-resolution community detection based on generalized self-loop rescaling strategy

Community detection is of considerable importance for analyzing the structure and function of complex networks. Many real-world networks may possess community structures at multiple scales, and recently, various multi-resolution methods were proposed to identify the community structures at different scales. In this paper, we present a type of multi-resolution methods by using the generalized self-loop rescaling strategy. The self-loop rescaling strategy provides one uniform ansatz for the design of multi-resolution community detection methods. Many quality functions for community detection can be unified in the framework of the self-loop rescaling. The resulting multi-resolution quality functions can be optimized directly using the existing modularity-optimization algorithms. Several derived multi-resolution methods are applied to the analysis of community structures in several synthetic and real-world networks. The results show that these methods can find the pre-defined substructures in synthetic networks and real splits observed in real-world networks. Finally, we give a discussion on the methods themselves and their relationship. We hope that the study in the paper can be helpful for the understanding of the multi-resolution methods and provide useful insight into designing new community detection methods.

Impact of high fat diet on long non-coding RNAs and messenger RNAs expression in the aortas of ApoE(−/−) mice

Atherosclerosis is a chronic multifactorial inflammatory disease with high prevalence worldwide, and has become the leading cause of death. The present study was designed to investigate the impact of high-fat diet on ApoE(−/−) mice exhibiting atherosclerosis by detecting the genome-wide expression profile of lncRNAs and mRNAs. A total of 354 differentially expressed lncRNAs were identified (≥2.0 folds). Simultaneously, 357 differentially expressed mRNAs from the same chip were found. The expression differences of lncRNAs and mRNAs were consistent in both qPCR and microarray detection. Annotation results of the mRNAs which correlated with lncRNAs showed that the commonly related pathways were metabolism and inflammation. Hypergeometric distribution analysis indicated that the differentially expressed lncRNAs had been mostly regulated by transcription factors (TFs) such as Myod1, Rxra, Pparg, Tcf3, etc. Additional lncRNA-target-TFs network analysis was conducted for the top 20 differentially expressed lncRNAs. The results indicated Hnf4a, Ppara, Vdr, and Runx3 as the TFs most likely to regulate the production of these lncRNAs, and might play roles in inflammatory and metabolic processes in atherosclerosis. In a nutshell, the present study identified a panel of dysregulated lncRNAs and mRNAs that may be potential biomarkers or drug targets relevant to the high-fat diet related atherogenesis.

Enhancing community detection by using local structural information

Many real-world networks, such as gene networks, protein–protein interaction networks and metabolic networks, exhibit community structures, meaning the existence of groups of densely connected vertices in the networks. Many local similarity measures in the networks are closely related to the concept of the community structures, and may have a positive effect on community detection in the networks. Here, various local similarity measures are used to extract local structural information, which is then applied to community detection in the networks by using the edge-reweighting strategy. The effect of the local similarity measures on community detection is carefully investigated and compared in various networks. The experimental results show that the local similarity measures are crucial for the improvement of community detection methods, while the positive effect of the local similarity measures is closely related to the networks under study and applied community detection methods.

A Meta-Analysis of the Association between Polymorphisms in MicroRNAs and Risk of Ischemic Stroke.

Ischemic stroke (IS) is responsible for a high death rate and for adult disability worldwide. MiR-146a (rs2910164), miR-149 (rs2292832), miR-196a2 (rs11614913) and miR-499 (rs3746444) are found to be associated with ischemic stroke. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the four polymorphisms and IS risk. The databases Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database were searched for related studies. A total of five studies including 2230 cases and 2229 controls were identified for the meta-analysis. The results indicate that TT genotype and T allele of miR-149 (rs2292832) are associated with significantly lower risks of IS in a homozygous model (OR = 0.70) and an allelic model (OR = 0.86). No significant associations were found between miR-146a (rs2910164), miR-196a2 (rs11614913), miR-499 (3746444) and IS susceptibility in any of the studies. However, subgroup analysis by sample size indicates a significant decrease in risks of IS for CC genotype and C allele of miR-146a (rs2910164) in the large sample size group. Therefore, miR-149 (rs2292832) might be recommended as a predictor for IS risk, while miR-146a (rs2910164), miR-196a2 (rs11614913), miR-499 (3746444) are not.

Effects of triptolide on hippocampal microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimer's disease.

The principal pathology of Alzheimers disease includes neuronal extracellular deposition of amyloid-beta peptides and formation of senile plaques, which in turn induce neuroinflammation in the brain. Triptolide, a natural extract from the vine-like herb Tripterygium wilfordii Hook F, has potent anti-inflammatory and immunosuppressive efficacy. Therefore, we determined if triptolide can inhibit activation and proliferation of microglial cells and astrocytes in the APP/PS1 double transgenic mouse model of Alzheimers disease. We used 1 or 5 μg/kg/d triptolide to treat APP/PS1 double transgenic mice (aged 4-4.5 months) for 45 days. Unbiased stereology analysis found that triptolide dose-dependently reduced the total number of microglial cells, and transformed microglial cells into the resting state. Further, triptolide (5 μg/kg/d) also reduced the total number of hippocampal astrocytes. Our in vivo test results indicate that triptolide suppresses activation and proliferation of microglial cells and astrocytes in the hippocampus of APP/PS1 double transgenic mice with Alzheimers disease.

Meta-Analysis for the Association between Polymorphisms in Interleukin-17A and Risk of Coronary Artery Disease.

Coronary artery disease (CAD) is a disease which has become a leading cause of death worldwide. The polymorphisms in Interleukin-17 (IL-17A), including rs2275913, rs3819024, rs3819025, rs3748067, rs8193037, rs4711998, and rs8193036, have been found to be probably associated with the risk of CAD. However, the results were inconsistent and inconclusive. The present study performed a meta-analysis to get a more precise and comprehensive estimation of the association between the IL-17A polymorphisms and CAD risk. The Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Databases were searched for related studies. A total of six studies, including 3542 cases and 3212 controls, were identified for the meta-analysis. The main findings of the present meta-analysis show that the TT genotype of IL-17A rs3748067 is associated with a significant lower risk of CAD in the homozygous model odds ratio (OR) (OR = 0.37) in Asians. No significant association was found for rs2275913, rs3819024, rs3819025, rs8193037, rs4711998, and rs8193036 with CAD susceptibility in the overall analysis. However, subgroup analysis indicated a significant decreased risk of CAD for the GG genotype and G allele of rs2275913 in a small sample size group, and a higher risk of CAD for the GG genotype and G allele of rs8193037 in a heterozygous model (OR = 1.56), dominant model (OR = 1.54), and allelic model (OR = 1.47) in Asians. In conclusion, the current meta-analysis suggests a significant relationship between rs3748067, rs8193037, and CAD in Asians, while for rs2275913, rs3819024, rs3819025, rs4711998, rs8193036, no such relations were found. Thus, IL-17A rs3748067 and rs8193037 might be recommended as a predictor for susceptibility of CAD for Asians. However, the results of this meta-analysis are hypothesis-generating results which should be interpreted with caution because of the heterogeneity and publication bias among study designs.

Enhancing betweenness algorithm for detecting communities in complex networks

Community structure is an important topological property common to many social, biological and technological networks. First, by using the concept of the structural weight, we introduced an improved version of the betweenness algorithm of Girvan and Newman to detect communities in networks without (intrinsic) edge weight and then extended it to networks with (intrinsic) edge weight. The improved algorithm was tested on both artificial and real-world networks, and the results show that it can more effectively detect communities in networks both with and without (intrinsic) edge weight. Moreover, the technique for improving the betweenness algorithm in the paper may be directly applied to other community detection algorithms.

Rs4265085 in GPER1 gene increases the risk for unexplained recurrent spontaneous abortion in Dai and Bai ethnic groups in China

Oestrogen receptors are implicated in the pathogenesis of recurrent spontaneous abortion (RSA). Non-genomic oestrogen responses can be mediated by GPER. The prevalence of polymorphisms in GPER1 gene in RSA was assessed in 747 Chinese women from Yunnan province (171 Bai, 258 Chinese Han, 234 Dai, 33 Achang and 51 Jingpo patients). Snapshot technology was used for genotyping the polymorphisms of the GPER1 gene. The rs4265085G was significantly increased in the Dai and Bai groups versus controls (Dai: P < 0.0001, Padj < 0.0001, OR 95% CI 2.34 [1.79 to 3.05]; Bai: P = 0.0004, Padj = 0.0012, OR 95% CI 1.71 [1.27 to 2.31]); recessive model of rs4265085 in the Dai (P = 0.003, Padj = 0.009, OR 95% CI 2.71 [1.38 to 5.30]); Bai (P < 0.0001, Padj < 0.0001, OR 95% CI 3.37 [1.93 to 5.91]). Haplotype frequencies containing rs10269151G-rs4265085G-rs11544331C were separately significantly different in Dai and Bai ethnic groups (Dai: P = 0.0002, Padj = 0.001, OR 95% CI = 2.12 [1.43 to 3.17]; Bai: P = 0.005, Padj = 0.025, OR 95% CI = 1.82 [1.18 to 2.78]) compared with controls. The intron variant rs4265085 may confer risk for RSA in Dai and Bai ethnic groups.

TLR4 rs41426344 increases susceptibility of rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population

BackgroundThe aim of the study was to determine whether polymorphisms in toll-like receptor 4 (TLR4) confer susceptibility to rheumatoid arthritis (RA) and juvenile idiopathic arthritis (JIA) in a central south Chinese Han population.MethodsGenotyping for six well studied polymorphisms (rs4986790, rs4986791, rs10759932, rs41426344, rs11536889 and rs7873784) in TLR4 gene were conducted in 1074 unrelated patients with RA and 1692 healthy control subjects, as well as in 217 unrelated patients with JIA and 378 healthy control subjects using direct sequencing technique. Comparisons between cases and controls in alleles, genotypes and haplotypes were carried out using Fisher’s exact test.ResultsSignificant genetic associations were detected between the 3’UTR rs41426344C and RA (p < 0.001, padj < 0.001, OR = 2.24) and JIA (p < 0.001, padj < 0.001, OR = 2.05). In addition, rs4986790G was found to be significantly associated with the susceptibility for RA (p = 0.005, padj = 0.03, OR = 3.43), but not for JIA (p = 0.06, padj = 0.36, OR = 2.65). Furthermore, significant increasing in the distributions of haplotypes H4 and H10 in RA (H4: p = 0.001, OR = 1.13; H10: p = 0.001, OR = 1.15) and JIA (H4: p = 0.04, OR = 2.06; H10: p = 0.02, OR = 2.47) were also found. Moreover, the frequency of rs41426344C significantly increased in RF-positive and anti-CCP positive subjects both in RA (RF+: p <0.0001, OR = 2.33; anti-CCP+: p =0.008, OR = 2.79) and JIA (RF+: p =0.02, OR = 2.91; anti-CCP+: p = 0.02, OR = 2.78).ConclusionsOur study suggested that rs41426344 and rs4986790 of TLR4 might contribute to RA, and rs41426344 might contribute to JIA pathogenesis in central south Chinese Han population.

Meta-Analysis on the Association of ALDH2 Polymorphisms and Type 2 Diabetic Mellitus, Diabetic Retinopathy

Type 2 diabetic mellitus (T2DM) is a disease with high prevalence and a major cause for death worldwide. Diabetic retinopathy (DR) is one of the major manifestation of diabetes. Aldehyde dehydrogenease 2 (ALDH2) detoxifies aldehyde produced during ethanol metabolism and oxidative stress. It has been found that the polymorphism in ALDH2 rs671 is probably associated with the risk of T2DM and DR. However, a lot of inconsistency and controversy still exists. In order to get a more precise and comprehensive estimation for the association between ALDH2 polymorphism with the risk of T2DM and DR, we conducted the present meta-analysis. A comprehensive literature search was conducted using databases, such as Pubmed, Embase, Cochrane Central Register of Controlled Trials, Chinese National Knowledge Infrastructure, and Chinese Biomedical Literature Database, for all related studies. The included studies met the inclusion criteria, such as being case-control studies about the association of ALDH2 polymorphism and T2DM or DR susceptibility, with sufficient data for the present analysis. Eight studies with 2374 cases and 6694 controls were involved in the present meta-analysis. The results indicated a significant lower risk of T2DM for *1/*1 genotype in homozygous models (*1/*1 vs. *2/*2, OR = 0.31, 95% CI = 0.11–0.89, p = 0.03) and in the dominant model (*1/*1 vs. *2/*2 + *1/*2, OR = 0.61, 95% CI = 0.37–1.00, p = 0.05). Subgroup analysis by ethnicity found a significant lower risk of T2DM in Chinese in all genotype models. No significant relation was found between ALDH2 rs671 and DR. In conclusion, the current meta-analysis indicated that ALDH2 rs671 was significantly related with T2DM. The ALDH2 rs671 might be able to be used as a predictor for the risk of T2DM. However, due to the existence of heterogeneity and publication bias in the involved studies, our results should be interpreted with caution.