Discovering Gene Co-Expression Modules Using Fuzzified Adjusted Rand Index
Taiwo Adigun,
Angela Makolo
Issue:
Volume 7, Issue 2, December 2019
Pages:
11-21
Received:
20 May 2019
Accepted:
24 June 2019
Published:
6 August 2019
Abstract: Understanding the interrelationship among genes in a cellular system is fundamental to the investigation of cellular activities, because the interrelated genes are either functionally related, controlled by the same transcriptional regulatory process or generally take part in a common biological process, and most importantly are known to be co-expressed genes. Most latent Mtb genes have been discovered but their functions, interrelationship and correlations that will help to develop protocol (s) to tame the menace of tuberculosis disease at latency have not been fully uncovered. We have developed a computational technique called Fuzzified Adjusted Rand Index (FARI) to effectively discover the co-expressed genes from identified latent Mtb genes and perform functional analysis of the gene sets using an annotation database. FARI, a modification of Adjusted Rand index used to compare clustering results, is designed to analyze, establish and quantify the expression trend of two genes with different sample points. Rank matrix of all the genes in consideration is produced after each gene has been analyzed with others, and the rank matrix serves as the basis of the co-expression discovery. A synthetic gene expression dataset, the biological benchmark dataset (E. coli), and different set of genes containing latent Mtb genes from an experiment result were fed into the computational tool, and different gene sets (modules) representing co-expressed genes were discovered. The discovered gene modules from latent Mtb genes are used to uncover the hub genes and their molecular functions. We have been able to identify different co-expression network from this analysis and assign biological functional meanings to some of the important Mtb genes that emerge from the experiment. Also, discovering gene co-expression module births gene co-expression network, which is a preliminary step towards gene regulatory network discovery.
Abstract: Understanding the interrelationship among genes in a cellular system is fundamental to the investigation of cellular activities, because the interrelated genes are either functionally related, controlled by the same transcriptional regulatory process or generally take part in a common biological process, and most importantly are known to be co-expr...
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Identification of a Novel Gene, Slc39a8, Encoding Zinc Transporter Specific to Treg Cells by Integrative Bioinformatic Analysis and Its Functional Validation
Dong Woo Ko,
Jeesang Yoon,
Jung Jin Yang
Issue:
Volume 7, Issue 2, December 2019
Pages:
22-29
Received:
21 November 2019
Accepted:
9 December 2019
Published:
4 January 2020
Abstract: Regulatory T cell (Treg cell) is a subset of T cell expressing Foxp3 transcription factor and critical for maintaining the immunological homeostasis in autoimmune micro-environment. However, the absence of the surface marker specific to Treg cell is the major barrier for the development of therapeutic reagent targeting Treg cells. To identify a novel gene specific to Treg cells mRNA sequencing data about naïve T cell, activated T cells (Th0), TH1 and Treg cells were processed by integrative bioinformatic methods and 350 Differentially Expressed Genes (DEGs) specific to Treg cells were selected. Using the bioinformatic program to score the intracellular location and functional gene network analysis to measure the functional relationship to Foxp3 Slc39a8 gene encoding zinc transport on the surface of Treg cells was chosen as a final candidate. The protein expression of the Slc39a8 gene was highly specific to Treg cells among various T cell subsets, and its expression was induced by TGF-β. In a dose-dependent manner, which is the key immuno-suppressive cytokine. The immuno-suppressive capacity of CD4+/Slc39a8+ T cells toward the activated T cells was substantially higher than that of CD4+/CD25+ T cells in a contact-independent way. Taken these results together, Slc39a8 was identified as a novel Treg cell-specific marker encoding a zinc transporter on the surface, which is functionally important for Treg cells. Therefore, Slc39a8 will serve as a new target molecule to develop the therapeutics for the treatment of various autoimmune diseases and solid cancers.
Abstract: Regulatory T cell (Treg cell) is a subset of T cell expressing Foxp3 transcription factor and critical for maintaining the immunological homeostasis in autoimmune micro-environment. However, the absence of the surface marker specific to Treg cell is the major barrier for the development of therapeutic reagent targeting Treg cells. To identify a nov...
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