Identifying the hub genes for Duchenne muscular dystrophy and Becker muscular dystrophy by weighted correlation network analysis

Background The goal of this study is to identify the hub genes for Duchenne muscular dystrophy (DMD) and Becker muscular dystrophy (BMD) via weighted correlation network analysis (WGCNA). Methods The gene expression profile of vastus lateralis biopsy samples obtained in 17 patients with DMD, 11 patients with BMD and 6 healthy individuals was downloaded from the Gene Expression Omnibus (GEO) database (GSE109178). After obtaining different expressed genes (DEGs) via GEO2R, WGCNA was conducted using R package, modules and genes that highly associated with DMD, BMD, and their age or pathology were screened. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) enrichment analysis and protein–protein interaction (PPI) network analysis were also conducted. Hub genes and highly correlated clustered genes were identified using Search Tool for the Retrieval of Interacting Genes (STRING) and Cystoscape software. Results One thousand four hundred seventy DEGs were identified between DMD and control, with 1281 upregulated and 189 downregulated DEGs. Four hundred and twenty DEGs were found between BMD and control, with 157 upregulated and 263 upregulated DEGs. Fourteen modules with different colors were identified for DMD vs control, and 7 modules with different colors were identified for BMD vs control. Ten hub genes were summarized for DMD and BMD respectively, 5 hub genes were summarized for BMD age, 5 and 3 highly correlated clustered genes were summarized for DMD age and BMD pathology, respectively. In addition, 20 GO enrichments were found to be involved in DMD, 3 GO enrichments were found to be involved in BMD, 3 GO enrichments were found to be involved in BMD age. Conclusion In DMD, several hub genes were identified: C3AR1, TLR7, IRF8, FYB and CD33(immune and inflammation associated genes), TYROBP, PLEK, AIF1(actin reorganization associated genes), LAPTM5 and NT5E(cell death and arterial calcification associated genes, respectively). In BMD, a number of hub genes were identified: LOX, ELN, PLEK, IKZF1, CTSK, THBS2, ADAMTS2, COL5A1(extracellular matrix associated genes), BCL2L1 and CDK2(cell cycle associated genes).

Metabolome and Transcriptome Reveal Novel Formation Mechanism of Early Mature Trait in Kiwifruit (Actinidia eriantha)

Kiwifruit (Actinidia eriantha) is a peculiar berry resource in China, and the maturation period is generally late. Fortunately, we found an early mature A. eriantha germplasm. In order to explore the formation mechanism of its early mature trait, we determined the main carbohydrate and endogenous hormone content of the fruit, and used off-target metabolomics and transcriptomics to identify key regulatory metabolites and genes. We found that early mature germplasm had faster starch conversion rate and higher sucrose, glucose, and fructose content when harvested, while with lower auxin (IAA), abscisic acid (ABA), and zeatin (ZR) content. Through the non-targeted metabolome, 19 and 20 metabolites closely related to fruit maturity and early maturity were identified, respectively. At the same time, weighted correlation network analysis (WGCNA) showed that these metabolites were regulated by 73 and 99 genes, respectively, especially genes related to sugar metabolism were mostly. Based on above, the formation of early mature trait of A. eriantha was mainly due to the sucrose decomposition rate was reduced and the soluble solid content (SSC) accumulated at low levels of endogenous hormones, so as to reach the harvest standard earlier than the late mature germplasm. Finally, ten single nucleotide polymorphism (SNP) loci were developed which can be used for the identification of early mature trait of A. eriantha.

Identification of Key Ischemic Stroke Genes by Computational Systems Biology

Stroke is one of the leading causes of death in humans. Even if patients survive from stroke, they may suffer sequelae such as disability. Treatment for strokes remains unsatisfactory due to an incomplete understanding of its mechanisms. This study investigates Ischemic Stroke (IS), a primary subtype of stroke, through analyses based on microarray data. Limma (in R)derives differentially expressed genes, and the protein-protein interaction (PPI) network is mapped from the database. Gene co-expression patterns are obtained for clustering gene modules by the Weighted Correlation Network Analysis (WGCNA), and genes with high connectivity in the significantly co-expressed modules are selected as key regulators. Common hubs are identified as Cdkn1a, Nes and Anxa2. Based on our analyses, we hypothesize that these hubs might play a key role in the onset and progression of IS. Result suggests the potential of identifying unexplored key regulators by the systemic method used in this work. Further analyses aim at expanding candidate genes for screening biomarkers for IS, and experimental validation is required on identified potential hubs.

Immune classification and identification of prognostic genes for uveal melanoma based on six immune cell signatures

Cutaneous melanoma could be treated by immunotherapy, which only has limited efficacy on uveal melanoma (UM). UM immunotyping for predicting immunotherapeutic responses and guiding immunotherapy should be better understood. This study identified molecular subtypes and key genetic markers associated with immunotherapy through immunosignature analysis. We screened a 6-immune cell signature simultaneously correlated with UM prognosis. Three immune subtypes (IS) were determined based on the 6-immune cell signature. Overall survival (OS) of IS3 was the longest. Significant differences of linear discriminant analysis (LDA) score were detected among the three IS types. IS3 with the highest LDA score showed a low immunosuppression. IS1 with the lowest LDA score was more immunosuppressive. LDA score was significantly negatively correlated with most immune checkpoint-related genes, and could reflect UM patients’ response to anti-PD1 immunotherapy. Weighted correlation network analysis (WGCNA) identified that salmon, purple, yellow modules were related to IS and screened 6 prognostic genes. Patients with high-expressed NME1 and TMEM255A developed poor prognosis, while those with high-expressed BEX5 and ROPN1 had better prognosis. There was no notable difference in OS between patients with high-expressed LRRN1 and ST13 and those with low-expressed LRRN1 and ST13. NME1, TMEM255A, Bex5 and ROPN1 showed potential prognostic significance in UM.

Identification of Key Ischemic Stroke Genes by Computational Systems Biology

Stroke is one of the leading causes of death in humans. Even if patients survive from stroke, they may suffer sequelae such as disability. Treatment for strokes remains unsatisfactory due to an incomplete understanding of its mechanisms. This study investigates Ischemic Stroke (IS), a primary subtype of stroke, through analyses based on microarray data. Limma (in R)derives differentially expressed genes, and the protein-protein interaction (PPI) network is mapped from the database. Gene co-expression patterns are obtained for clustering gene modules by the Weighted Correlation Network Analysis (WGCNA), and genes with high connectivity in the significantly co-expressed modules are selected as key regulators. Common hubs are identified as Cdkn1a, Nes and Anxa2. Based on our analyses, we hypothesize that these hubs might play a key role in the onset and progression of IS. Result suggests the potential of identifying unexplored key regulators by the systemic method used in this work. Further analyses aim at expanding candidate genes for screening biomarkers for IS, and experimental validation is required on identified potential hubs.

Environmental characteristics and changes of bacterial communities in the meltwater runoff of glacier in Ny-Alesund, Arctic

The present study assessed the diversity and composition of bacterial communities in glacial runoff and glacial soils in the Midre Lovénbreen glacier region of Svalbard. A total of 6,593 operational taxonomic units were identified by high-throughput sequencing. The results showed differences in bacterial community composition between the upper and lower reaches of glacial runoff. The abundance of Actinobacteria, Firmicutes, Betaproteobacteria and Gammaproteobacteria in the upper reaches of glacial runoff was higher than that in the lower reaches. In contrast, the the abundance of Cyanobacteria and Alphaproteobacteria in the downstream of glacial runoff was higher than that in the upstream. In addition, we compared bacterial diversity and composition between glacial runoff areas and soils. The chart analysis showed that bacterial diversity in glacial soil was higher than that in the glacial runoff. Some typical bacteria in the soil, such as Actinobacteria, entered glacial runoff through contact between them. The abundance of Acidobacteria, Sphingobacterium and Flavobacterium was higher in glacial soil. Weighted correlation network analysis showed that the core bacteria in glacial runoff and glacial soil were typical bacteria in different habitats. Distance-based redundancy analysis revealed that NO 2 - -N was the most significant factor affecting the distribution of soil bacterial community, while NO 3 - -N was the most significant factor affecting the distribution of glacial runoff bacterial community.

Correlation coefficients of credibility interval-valued neutrosophic sets and their group decision-making method in single- and interval-valued hybrid neutrosophic multi-valued environment

Although a single-valued neutrosophic multi-valued set (SVNMVS) can reasonably and perfectly express group evaluation information and make up for the flaw of multi-valued/hesitant neutrosophic sets in group decision-making problems, its information expression and group decision-making methods still lack the ability to express and process single- and interval-valued hybrid neutrosophic multi-valued information. To overcome the drawbacks, this study needs to propose single- and interval-valued hybrid neutrosophic multi-valued sets (SIVHNMVSs), correlation coefficients of consistency interval-valued neutrosophic sets (CIVNSs), and their multi-attribute group decision-making (MAGDM) method in the setting of SIVHNMVSs. First, we propose SIVHNMVSs and a transformation method for converting SIVHNMVSs into CIVNSs based on the mean and consistency degree (the complement of standard deviation) of truth, falsity and indeterminacy sequences. Then, we present two correlation coefficients between CIVNSs based on the multiplication of both the correlation coefficient of interval-valued neutrosophic sets and the correlation coefficient of neutrosophic consistency sets and two weighted correlation coefficients of CIVNSs. Next, a MAGDM method is developed based on the proposed two weighted correlation coefficients of CIVNSs for performing MAGDM problems under the environment of SIVHNMVSs. At last, a selection case of landslide treatment schemes demonstrates the application of the proposed MAGDM method under the environment of SIVHNMVSs. By comparative analysis, our new method not only overcomes the drawbacks of the existing method, but also is more extensive and more useful than the existing method when tackling MAGDM problems in the setting of SIVHNMVSs.

Investigation of Local Weighting Filtering on Randomization Technique Estimates in a Data Assimilation System

Mainstream numerical weather prediction (NWP) centers usually estimate the standard deviations of background error by using a randomization technique to calibrate specific parameters of the background error covariance model in variational data assimilation (VAR) systems. However, the sampling size of the randomization technique is typically several orders of magnitude smaller than that of model state variables, and using finite-sized estimates as a proxy for the truth can lead to sampling noise, which may contaminate the estimation of the standard deviation. The sampling noise is firstly investigated in an atmospheric model to show that the sampling noise has a symmetrical structure oscillating around the truth on a small scale. To alleviate the sampling noise, a heterogeneous local weighting filtering is proposed based on distance-weighted correlation and similarity-weighted correlation. Local weighting filtering is easy to implement in the VAR operational systems and has a low computational cost in the post-processing of reducing the sampling noise. The validity and performance of local weighting filtering method are examined in a realistic model framework to show that the proposed filtering is able to eliminate most of the sampling noise dramatically, the details of the filtered results are more visible, and the accuracy of the filtered results is almost the same as that estimated from the larger sample. The signal-to-noise ratio of the optimal filtered field is improved by nearly 20%. A comparison with the widely used spectral filtering approach in the operational system is considered, showing that the proposed filtering method is more efficient to implement in the filtering procedure and exhibits very good performance in terms of preserving the local anisotropic features of the estimates. These attractive results show the potential efficiency of the local weighting filtering method for solving the noise issue in the randomization technique.