UICPC: Centrality-based clustering for scRNA-seq data analysis without user input.

scRNA-seq data analysis enables new possibilities for identification of novel cells, specific characterization of known cells and study of cell heterogeneity. The performance of most clustering methods especially developed for scRNA-seq is greatly influenced by user input. We propose a centrality-clustering method named UICPC and compare its performance with 9 state-of-the-art clustering methods on 11 real-world scRNA-seq datasets to demonstrate its effectiveness and usefulness in discovering cell groups. Our method does not require user input. However, it requires settings of threshold, which are benchmarked after performing extensive experiments. We observe that most compared approaches show poor performance due to high heterogeneity and large dataset dimensions. However, UICPC shows excellent performance in terms of NMI, Purity and ARI, respectively. UICPC is available as an R package and can be downloaded by clicking the link https://sites.google.com/view/hussinchowdhury/software.

Differential Expression Analysis of RNA-seq Reads: Overview, Taxonomy, and Tools.

Analysis of RNA-sequence (RNA-seq) data is widely used in transcriptomic studies and it has many applications. We review RNA-seq data analysis from RNA-seq reads to the results of differential expression analysis. In addition, we perform a descriptive comparison of tools used in each step of RNA-seq data analysis along with a discussion of important characteristics of these tools. A taxonomy of tools is also provided. A discussion of issues in quality control and visualization of RNA-seq data is also included along with useful tools. Finally, we provide some guidelines for the RNA-seq data analyst, along with research issues and challenges which should be addressed.

(Differential) Co-Expression Analysis of Gene Expression: A Survey of Best Practices.

Analysis of gene expression data is widely used in transcriptomic studies to understand functions of molecules inside a cell and interactions among molecules. Differential co-expression analysis studies diseases and phenotypic variations by finding modules of genes whose co-expression patterns vary across conditions. We review the best practices in gene expression data analysis in terms of analysis of (differential) co-expression, co-expression network, differential networking, and differential connectivity considering both microarray and RNA-seq data along with comparisons. We highlight hurdles in RNA-seq data analysis using methods developed for microarrays. We include discussion of necessary tools for gene expression analysis throughout the paper. In addition, we shed light on scRNA-seq data analysis by including preprocessing and scRNA-seq in co-expression analysis along with useful tools specific to scRNA-seq. To get insights, biological interpretation and functional profiling is included. Finally, we provide guidelines for the analyst, along with research issues and challenges which should be addressed.

Integrative network analysis identifies differential regulation of neuroimmune system in Schizophrenia and Bipolar disorder.

Background: Neuropsychiatric disorders such as Schizophrenia (SCZ) and Bipolar disorder (BPD) pose a broad range of problems with different symptoms mainly characterized by some combination of abnormal thoughts, emotions, behaviour, etc. However, in depth molecular and pathophysiological mechanisms among different neuropsychiatric disorders have not been clearly understood yet. We have used RNA-seq data to investigate unique and overlapping molecular signatures between SCZ and BPD using an integrative network biology approach. Methods: RNA-seq count data were collected from NCBI-GEO database generated on post-mortem brain tissues of controls (n = 24) and patients of BPD (n = 24) and SCZ (n = 24). Differentially expressed genes (DEGs) were identified using the consensus of DESeq2 and edgeR tools and used for downstream analysis. Weighted gene correlation networks were constructed to find non-preserved (NP) modules for SCZ, BPD and control conditions. Topological analysis and functional enrichment analysis were performed on NP modules to identify unique and overlapping expression signatures during SCZ and BPD conditions. Results: We have identified four NP modules from the DEGs of BPD and SCZ. Eleven overlapping genes have been identified between SCZ and BPD networks, and they were found to be highly enriched in inflammatory responses. Among these eleven genes, TNIP2, TNFRSF1A and AC005840.1 had higher sum of connectivity exclusively in BPD network. In addition, we observed that top five genes of NP module from SCZ network were downregulated which may be a key factor for SCZ disorder. Conclusions: Differential activation of the immune system components and pathways may drive the common and unique pathogenesis of the BPD and SCZ.