Miao Chen

Background: Clinically, behavior, cognitive, and mental functions are affected during the neurodegenerative disease progression. To date, the molecular pathogenesis of these complex disease is still unclear. With the rapid development of sequencing technologies, it is possible to delicately decode the molecular mechanisms corresponding to different clinical phenotypes at the genome-wide transcriptomic level using computational methods. Our previous studies have shown that it is difficult to distinguish disease genes from non-disease genes. Therefore, to precisely explore the molecular pathogenesis under complex clinical phenotypes, it is better to identify biomarkers corresponding to different disease stages or clinical phenotypes. So, in this study, we designed a label propagation-based semi-supervised feature selection approach (LPFS) to prioritize disease-associated genes corresponding to different disease stages or clinical phenotypes.Methods: In this study, we pioneering put label propagation clustering and feature selection into one framework and proposed label propagation-based semi-supervised feature selection approach. LPFS prioritizes disease genes related to different disease stages or phenotypes through the alternative iteration of label propagation clustering based on sample network and feature selection with gene expression profiles. Then the GO and KEGG pathway enrichment analysis were carried as well as the gene functional analysis to explore molecular mechanisms of specific disease phenotypes, thus to decode the changes in individual behavioral and mental characteristics during neurodegenerative disease progression.Results: Large amounts of experiments were conducted to verify the performance of LPFS with Huntington’s gene expression data. Experimental results shown that LPFS performs better in comparison with the-state-of-art methods. GO and KEGG enrichment analysis of key gene sets shown that TGF-beta signaling pathway, cytokine-cytokine receptor interaction, immune response, and inflammatory response were gradually affected during the Huntington’s disease progression. In addition, we found that the expression of SLC4A11, ZFP474, AMBP, TOP2A, PBK, CCDC33, APSL, DLGAP5, and Al662270 changed seriously by the development of the disease.Conclusions: In this study, we designed a label propagation-based semi-supervised feature selection model to precisely selected key genes of different disease phenotypes. We conducted experiments using the model with Huntington’s disease mice gene expression data to decode the mechanisms of it. We found many cell types, including astrocyte, microglia, and GABAergic neuron, could be involved in the pathological process.

Background: Huntington’s disease is a kind of chronic progressive neurodegenerative disease with complex pathogenic mechanisms. To data, the pathogenesis of Huntington’s disease is still not fully understood, and there has been no effective treatment. The rapid development of high-throughput sequencing technologies makes it possible to explore the molecular mechanisms at the transcriptome level. Our previous studies on Huntington’s disease have shown that it is difficult to distinguish disease-associated genes from non-disease genes. Meanwhile, recent progress in bio-medicine shows that the molecular origin of chronic complex diseases may not exist in the diseased tissue, and differentially expressed genes between different tissues may be helpful to reveal the molecular origin of chronic diseases. Therefore, developing integrative analysis computational methods for the multi-tissues gene expression data, exploring the relationship between differentially expressed genes in different tissues and the disease, can greatly accelerate the molecular discovery process.Methods: For analysis of the intra- and inter- tissues’ differentially expressed genes, we designed an integrative enrichment analysis method based on an artificial neuron (IEAAN). Firstly, we calculated the differential expression scores of genes which are seen as features of the corresponding gene, using fold-change approach with intra- and inter- tissues’ gene expression data. Then, we weighted sum all the differential expression scores through a sigmoid function to get differential expression enrichment score. Finally, we ranked the genes according to the enrichment score. Top ranking genes are supposed to be the potential disease-associated genes.Results: In this study, we conducted large amounts of experiments to analyze the differentially expressed genes of intra- and inter- tissues. Experimental results showed that genes differentially expressed between different tissues are more likely to be Huntington’s disease-associated genes. Five disease-associated genes were selected out in this study, two of which have been reported to be implicated in Huntington’s disease.Conclusions: We proposed a novel integrative enrichment analysis method based on artificial neuron (IEAAN), which displays better prediction precision of disease-associated genes in comparison with the state-of-the-art statistical-based methods. Our comprehensive evaluation suggests that genes differentially expressed between striatum and liver tissues of health individuals are more likely to be Huntington’s disease-associated genes.

Schizophrenia (SCZ) is a severe chronic psychiatric illness with heterogeneous symptoms. However, the pathogenesis of SCZ is unclear, and the number of well-defined SCZ risk factors is limited. We hypothesized that an abnormal behavior (AB) gene set verified by mouse model experiments can be used to better understand SCZ risks. In this work, we carried out an integrative bioinformatics analysis to study two types of risk genes that are either differentially expressed (DEGs) in the case-control study data or carry reported SCZ genetic variants (MUTs). Next, we used RNA-Seq expression data from the hippocampus (HIPPO) and dorsolateral prefrontal cortex (DLPFC) to define the key genes affected by different types (DEGs and MUTs) in different brain regions (DLPFC and HIPPO): DLPFC-kDEG, DLPFC-kMUT, HIPPO-kDEG, and HIPPO-kMUT. The four hub genes (SHANK1, SHANK2, DLG4, and NLGN3) of the biological functionally enriched terms were strongly linked to SCZ via gene co-expression network analysis. Then, we observed that specific spatial expressions of DLPFC-kMUT and HIPPO-kMUT were convergent in the early stages and divergent in the later stages of development. In addition, all four types of key genes showed significantly larger average protein–protein interaction degrees than the background. Comparing the different cell types, the expression of four types of key genes showed specificity in different dimensions. Together, our results offer new insights into potential risk factors and help us understand the complexity and regional heterogeneity of SCZ.

Objective. The aim of this study was to identify the candidate genes in type 2 diabetes mellitus (T2DM) and explore their potential mechanisms. Methods. The gene expression profile GSE26168 was downloaded from the Gene Expression Omnibus (GEO) database. The online tool GEO2R was used to obtain differentially expressed genes (DEGs). Gene Ontology (GO) term enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis were performed by using Metascape for annotation, visualization, and comprehensive discovery. The protein-protein interaction (PPI) network of DEGs was constructed by using Cytoscape software to find the candidate genes and key pathways. Results. A total of 981 DEGs were found in T2DM, including 301 upregulated genes and 680 downregulated genes. GO analyses from Metascape revealed that DEGs were significantly enriched in cell differentiation, cell adhesion, intracellular signal transduction, and regulation of protein kinase activity. KEGG pathway analysis revealed that DEGs were mainly enriched in the cAMP signaling pathway, Rap1 signaling pathway, regulation of lipolysis in adipocytes, PI3K-Akt signaling pathway, MAPK signaling pathway, and so on. On the basis of the PPI network of the DEGs, the following 6 candidate genes were identified: PIK3R1, RAC1, GNG3, GNAI1, CDC42, and ITGB1. Conclusion. Our data provide a comprehensive bioinformatics analysis of genes, functions, and pathways, which may be related to the pathogenesis of T2DM.

Comprehensive bioinformatics analysis of the characterization and determination underlying mechanisms of over-expression and co-expression of genes residing on 20q in colorectal cancer Comprehensive bioinformatics analysis of the characterization and determination underlying mechanisms of over-expression and co-expression of genes residing on 20q in colorectal cancer