Identification of diagnostic biomarkers via weighted correlation network analysis in colorectal cancer using a system biology approach

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Abstract

Colorectal cancer (CRC) is the third most frequent cancer to be diagnosed in both females and males necessitating identification of effective biomarkers. An in-silico system biology approach called weighted gene co-expression network analysis (WGCNA) can be used to examine gene expression in a complicated network of regulatory genes. In the current study, the co-expression network of DEGs connected to CRC and their target genes was built using the WGCNA algorithm. GO and KEGG pathway analysis were carried out to learn more about the biological role of the DEmRNAs. These findings revealed that the genes were mostly enriched in the biological processes that were involved in the regulation of hormone levels, extracellular matrix organization, and extracellular structure organization. The intersection of genes between hub genes and DEmRNAs showed that DKC1, PA2G4, LYAR and NOLC1 were the clinically final hub genes of CRC.

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limma powers differential expression analyses for RNA-sequencing and microarray studies

Matthew E. Ritchie, Belinda Phipson, Di Wu … (2015)

limma is an R/Bioconductor software package that provides an integrated solution for analysing data from gene expression experiments. It contains rich features for handling complex experimental designs and for information borrowing to overcome the problem of small sample sizes. Over the past decade, limma has been a popular choice for gene discovery through differential expression analyses of microarray and high-throughput PCR data. The package contains particularly strong facilities for reading, normalizing and exploring such data. Recently, the capabilities of limma have been significantly expanded in two important directions. First, the package can now perform both differential expression and differential splicing analyses of RNA sequencing (RNA-seq) data. All the downstream analysis tools previously restricted to microarray data are now available for RNA-seq as well. These capabilities allow users to analyse both RNA-seq and microarray data with very similar pipelines. Second, the package is now able to go past the traditional gene-wise expression analyses in a variety of ways, analysing expression profiles in terms of co-regulated sets of genes or in terms of higher-order expression signatures. This provides enhanced possibilities for biological interpretation of gene expression differences. This article reviews the philosophy and design of the limma package, summarizing both new and historical features, with an emphasis on recent enhancements and features that have not been previously described.

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KEGG: kyoto encyclopedia of genes and genomes.

M Kanehisa (2000)

KEGG (Kyoto Encyclopedia of Genes and Genomes) is a knowledge base for systematic analysis of gene functions, linking genomic information with higher order functional information. The genomic information is stored in the GENES database, which is a collection of gene catalogs for all the completely sequenced genomes and some partial genomes with up-to-date annotation of gene functions. The higher order functional information is stored in the PATHWAY database, which contains graphical representations of cellular processes, such as metabolism, membrane transport, signal transduction and cell cycle. The PATHWAY database is supplemented by a set of ortholog group tables for the information about conserved subpathways (pathway motifs), which are often encoded by positionally coupled genes on the chromosome and which are especially useful in predicting gene functions. A third database in KEGG is LIGAND for the information about chemical compounds, enzyme molecules and enzymatic reactions. KEGG provides Java graphics tools for browsing genome maps, comparing two genome maps and manipulating expression maps, as well as computational tools for sequence comparison, graph comparison and path computation. The KEGG databases are daily updated and made freely available (http://www. genome.ad.jp/kegg/).

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WGCNA: an R package for weighted correlation network analysis

Peter Langfelder, Steve Horvath (2008)

Background Correlation networks are increasingly being used in bioinformatics applications. For example, weighted gene co-expression network analysis is a systems biology method for describing the correlation patterns among genes across microarray samples. Weighted correlation network analysis (WGCNA) can be used for finding clusters (modules) of highly correlated genes, for summarizing such clusters using the module eigengene or an intramodular hub gene, for relating modules to one another and to external sample traits (using eigengene network methodology), and for calculating module membership measures. Correlation networks facilitate network based gene screening methods that can be used to identify candidate biomarkers or therapeutic targets. These methods have been successfully applied in various biological contexts, e.g. cancer, mouse genetics, yeast genetics, and analysis of brain imaging data. While parts of the correlation network methodology have been described in separate publications, there is a need to provide a user-friendly, comprehensive, and consistent software implementation and an accompanying tutorial. Results The WGCNA R software package is a comprehensive collection of R functions for performing various aspects of weighted correlation network analysis. The package includes functions for network construction, module detection, gene selection, calculations of topological properties, data simulation, visualization, and interfacing with external software. Along with the R package we also present R software tutorials. While the methods development was motivated by gene expression data, the underlying data mining approach can be applied to a variety of different settings. Conclusion The WGCNA package provides R functions for weighted correlation network analysis, e.g. co-expression network analysis of gene expression data. The R package along with its source code and additional material are freely available at .

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Author and article information

Contributors

Mohammad Taheri: Mohammad.taheri@uni-jena.de

Elena Jamali: elena.jamali@yahoo.com

Journal

Journal ID (nlm-ta): Sci Rep

Journal ID (iso-abbrev): Sci Rep

Title: Scientific Reports

Publisher: Nature Publishing Group UK (London )

ISSN (Electronic): 2045-2322

Publication date (Electronic): 21 August 2023

Publication date PMC-release: 21 August 2023

Publication date Collection: 2023

Volume: 13

Electronic Location Identifier: 13637

Affiliations

[1 ]GRID grid.411600.2, Men’s Health and Reproductive Health Research Center, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran

[2 ]GRID grid.411600.2, Department of Medical Genetics, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran

[3 ]GRID grid.275559.9, ISNI 0000 0000 8517 6224, Institute of Human Genetics, , Jena University Hospital, ; Jena, Germany

[4 ]GRID grid.411600.2, Urology and Nephrology Research Center, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran

[5 ]GRID grid.411600.2, Department of Pathology, Loghman Hakim Hospital, , Shahid Beheshti University of Medical Sciences, ; Tehran, Iran

Article

Publisher ID: 40953

DOI: 10.1038/s41598-023-40953-5

PMC ID: 10442394

PubMed ID: 37604903

SO-VID: 0844900a-b7a2-47be-bbce-998761c05987

License:

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

History

Date received : 11 April 2023

Date accepted : 18 August 2023

Funding

Funded by: Universitätsklinikum Jena (8979)

Open Access :

Open Access funding enabled and organized by Projekt DEAL.

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ScienceOpen disciplines: Uncategorized

Keywords: cancer,genetics,molecular biology

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ScienceOpen disciplines: Uncategorized

Keywords: cancer, genetics, molecular biology

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Identification of diagnostic biomarkers via weighted correlation network analysis in colorectal cancer using a system biology approach

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Most cited references 34

limma powers differential expression analyses for RNA-sequencing and microarray studies

KEGG: kyoto encyclopedia of genes and genomes.

WGCNA: an R package for weighted correlation network analysis

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