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

Ghafouri-Fard, Soudeh; Safarzadeh, Arash; Taheri, Mohammad; Jamali, Elena

doi:10.1038/s41598-023-40953-5

Cited by 5 publications

(2 citation statements)

References 32 publications

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“…There are several TFs in their models across these digestive system tissues, but the most highly weighted TFs are RNA Polymerase I Subunit A (POLR1E) and genes from the Signal Transducer And Activator Of Transcription family STAT2, STAT3 and STAT4. Indeed, POLR1E is part of enriched signaling pathways in colorectal cancer [ 26 , 27 ] while these member of the STAT family are contributing to promotion of colorectal tumorigenesis, silencing them inhibits cell proliferation and invasion of colorectal cancer cells, and considered as targets for therapy [ 27 – 34 ].…”

Section: Resultsmentioning

confidence: 99%

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

Dagostino,

Gottlieb

2024

BMC Genomics

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Background Deciphering gene regulation is essential for understanding the underlying mechanisms of healthy and disease states. While the regulatory networks formed by transcription factors (TFs) and their target genes has been mostly studied with relation to cis effects such as in TF binding sites, we focused on trans effects of TFs on the expression of their transcribed genes and their potential mechanisms. Results We provide a comprehensive tissue-specific atlas, spanning 49 tissues of TF variations affecting gene expression through computational models considering two potential mechanisms, including combinatorial regulation by the expression of the TFs, and by genetic variants within the TF. We demonstrate that similarity between tissues based on our discovered genes corresponds to other types of tissue similarity. The genes affected by complex TF regulation, and their modelled TFs, were highly enriched for pharmacogenomic functions, while the TFs themselves were also enriched in several cancer and metabolic pathways. Additionally, genes that appear in multiple clusters are enriched for regulation of immune system while tissue clusters include cluster-specific genes that are enriched for biological functions and diseases previously associated with the tissues forming the cluster. Finally, our atlas exposes multilevel regulation across multiple tissues, where TFs regulate other TFs through the two tested mechanisms. Conclusions Our tissue-specific atlas provides hierarchical tissue-specific trans genetic regulations that can be further studied for association with human phenotypes.

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Section: Resultsmentioning

confidence: 99%

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

Dagostino,

Gottlieb

2024

BMC Genomics

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“…The degree of nodes in the PPI network is determined by the number of edges to which they are connected. Hub genes are identified as nodes with high degree values ( Ghafouri-Fard et al, 2023 ). We mapped the hub genes to examine their PPI details.…”

Section: Methodsmentioning

confidence: 99%

System biology approach to identify the novel biomarkers in glioblastoma multiforme tumors by using computational analysis

Alqahtani,

Altharawi,

Alabbas

et al. 2024

Front. Pharmacol.

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Introduction: The most common primary brain tumor in adults is glioblastoma multiforme (GBM), accounting for 45.2% of all cases. The characteristics of GBM, a highly aggressive brain tumor, include rapid cell division and a propensity for necrosis. Regretfully, the prognosis is extremely poor, with only 5.5% of patients surviving after diagnosis.Methodology: To eradicate these kinds of complicated diseases, significant focus is placed on developing more effective drugs and pinpointing precise pharmacological targets. Finding appropriate biomarkers for drug discovery entails considering a variety of factors, including illness states, gene expression levels, and interactions between proteins. Using statistical techniques like p-values and false discovery rates, we identified differentially expressed genes (DEGs) as the first step in our research for identifying promising biomarkers in GBM. Of the 132 genes, 13 showed upregulation, and only 29 showed unique downregulation. No statistically significant changes in the expression of the remaining genes were observed.Results: Matrix metallopeptidase 9 (MMP9) had the greatest degree in the hub biomarker gene identification, followed by (periostin (POSTN) at 11 and Hes family BHLH transcription factor 5 (HES5) at 9. The significance of the identification of each hub biomarker gene in the initiation and advancement of glioblastoma multiforme was brought to light by the survival analysis. Many of these genes participate in signaling networks and function in extracellular areas, as demonstrated by the enrichment analysis.We also identified the transcription factors and kinases that control proteins in the proteinprotein interactions (PPIs) of the DEGs.Discussion: We discovered drugs connected to every hub biomarker. It is an appealing therapeutic target for inhibiting MMP9 involved in GBM. Molecular docking investigations indicated that the chosen complexes (carmustine, lomustine, marimastat, and temozolomide) had high binding affinities of −6.3, −7.4, −7.7, and −8.7 kcal/mol, respectively, the mean root-mean-square deviation (RMSD) value for the carmustine complex and marimastat complex was 4.2 Å and 4.9 Å, respectively, and the lomustine and temozolomide complex system showed an average RMSD of 1.2 Å and 1.6 Å, respectively. Additionally, high stability in root-mean-square fluctuation (RMSF) analysis was observed with no structural conformational changes among the atomic molecules. Thus, these in silico investigations develop a new way for experimentalists to target lethal diseases in future.

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Revealing the role of serum exosomal novel long non-coding RNA NAMPT-AS as a promising diagnostic/prognostic biomarker in colorectal cancer patients

Rizk,

Kassem,

Abulsoud

et al. 2024

Life Sciences

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

Cited by 5 publications

References 32 publications

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

Tissue-specific atlas of trans-models for gene regulation elucidates complex regulation patterns

System biology approach to identify the novel biomarkers in glioblastoma multiforme tumors by using computational analysis

Revealing the role of serum exosomal novel long non-coding RNA NAMPT-AS as a promising diagnostic/prognostic biomarker in colorectal cancer patients

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