Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma

Background/aim: Multiple Myeloma (MM) is the second most common blood cancer, characterised by the accumulation of malignant plasma cells and the production of large amounts of a monoclonal immunoglobulin protein, in the bone marrow. The identification and progression/behaviour of molecular markers...

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Main Authors: Grigoris Georgiou, George Minadakis, Nestoras Karathanasis, Kyriaki Savva, Efi Athieniti, Marilena M. Bourdakou, George M. Spyrou
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Computational and Structural Biotechnology Journal
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Online Access:http://www.sciencedirect.com/science/article/pii/S2001037025002831
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author Grigoris Georgiou
George Minadakis
Nestoras Karathanasis
Kyriaki Savva
Efi Athieniti
Marilena M. Bourdakou
George M. Spyrou
author_facet Grigoris Georgiou
George Minadakis
Nestoras Karathanasis
Kyriaki Savva
Efi Athieniti
Marilena M. Bourdakou
George M. Spyrou
author_sort Grigoris Georgiou
collection DOAJ
description Background/aim: Multiple Myeloma (MM) is the second most common blood cancer, characterised by the accumulation of malignant plasma cells and the production of large amounts of a monoclonal immunoglobulin protein, in the bone marrow. The identification and progression/behaviour of molecular markers across stages remains a scientific challenge. This work aims to provide a holistic approach in the understanding of the disease progression through a computational approach, capable of characterising and distinguishing disease stages. Materials and methods: Stage-stratified MM transcriptomic datasets were used to mine stage-specific information and calculate key entities at the gene level by means of: (a) differentially expressed genes (DEGs), (b) monotonically expressed genes (MEGs), (c) ratios of MEG-related pairs of genes (RMEGs). The performance of the RMEGs across samples has been investigated regarding their ability to characterize and discriminate the MM stages. The genes participating in the top-ranked RMEGs were further used for pathway enrichment analysis to further enlighten the functional understanding per MM stage. Results: We show that the proposed computational methodology by means of RMEGs reveals short lists of key genes across stages, which in turn highlight significant groups of pathways associated with regulation and cell cycle. Conclusion: We integrate the traditional analysis of DEGs with the concepts of MEGs and RMEGs, creating a novel computational approach capable of identifying key genes and pathways that can serve as a highly-filtered pool of candidate MM stage identification markers for further experimental investigation.
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spelling doaj-art-6a3ebdffa3e145cb9e6f189dfd4fbdbf2025-08-20T03:27:58ZengElsevierComputational and Structural Biotechnology Journal2001-03702025-01-01273090309810.1016/j.csbj.2025.07.017Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple MyelomaGrigoris Georgiou0George Minadakis1Nestoras Karathanasis2Kyriaki Savva3Efi Athieniti4Marilena M. Bourdakou5George M. Spyrou6Corresponding authors.; Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusBioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusBioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusBioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusBioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusBioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusCorresponding authors.; Bioinformatics Department, The Cyprus Institute of Neurology & Genetics, 6 International Airport Avenue, 2370, P.O.Box 23462, Nicosia 1683, CyprusBackground/aim: Multiple Myeloma (MM) is the second most common blood cancer, characterised by the accumulation of malignant plasma cells and the production of large amounts of a monoclonal immunoglobulin protein, in the bone marrow. The identification and progression/behaviour of molecular markers across stages remains a scientific challenge. This work aims to provide a holistic approach in the understanding of the disease progression through a computational approach, capable of characterising and distinguishing disease stages. Materials and methods: Stage-stratified MM transcriptomic datasets were used to mine stage-specific information and calculate key entities at the gene level by means of: (a) differentially expressed genes (DEGs), (b) monotonically expressed genes (MEGs), (c) ratios of MEG-related pairs of genes (RMEGs). The performance of the RMEGs across samples has been investigated regarding their ability to characterize and discriminate the MM stages. The genes participating in the top-ranked RMEGs were further used for pathway enrichment analysis to further enlighten the functional understanding per MM stage. Results: We show that the proposed computational methodology by means of RMEGs reveals short lists of key genes across stages, which in turn highlight significant groups of pathways associated with regulation and cell cycle. Conclusion: We integrate the traditional analysis of DEGs with the concepts of MEGs and RMEGs, creating a novel computational approach capable of identifying key genes and pathways that can serve as a highly-filtered pool of candidate MM stage identification markers for further experimental investigation.http://www.sciencedirect.com/science/article/pii/S2001037025002831Multiple myelomaCancerPlasma cellsGammopathiesProgressionKey genes
spellingShingle Grigoris Georgiou
George Minadakis
Nestoras Karathanasis
Kyriaki Savva
Efi Athieniti
Marilena M. Bourdakou
George M. Spyrou
Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma
Computational and Structural Biotechnology Journal
Multiple myeloma
Cancer
Plasma cells
Gammopathies
Progression
Key genes
title Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma
title_full Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma
title_fullStr Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma
title_full_unstemmed Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma
title_short Stage-specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic Multiple Myeloma
title_sort stage specific gene pair ratios highlight genes and mechanisms related to presymptomatic and symptomatic multiple myeloma
topic Multiple myeloma
Cancer
Plasma cells
Gammopathies
Progression
Key genes
url http://www.sciencedirect.com/science/article/pii/S2001037025002831
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