Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)

Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnosti...

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Main Authors: Constantinos Yeles, Efstathios-Iason Vlachavas, Olga Papadodima, Eleftherios Pilalis, Constantinos E. Vorgias, Alexandros G. Georgakilas, Aristotelis Chatziioannou
Format: Article
Language:English
Published: MDPI AG 2017-11-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/9/12/160
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author Constantinos Yeles
Efstathios-Iason Vlachavas
Olga Papadodima
Eleftherios Pilalis
Constantinos E. Vorgias
Alexandros G. Georgakilas
Aristotelis Chatziioannou
author_facet Constantinos Yeles
Efstathios-Iason Vlachavas
Olga Papadodima
Eleftherios Pilalis
Constantinos E. Vorgias
Alexandros G. Georgakilas
Aristotelis Chatziioannou
author_sort Constantinos Yeles
collection DOAJ
description Ionizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.
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spelling doaj.art-df83f6da1f324adbbd476164138f4fd42023-09-02T17:48:33ZengMDPI AGCancers2072-66942017-11-0191216010.3390/cancers9120160cancers9120160Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)Constantinos Yeles0Efstathios-Iason Vlachavas1Olga Papadodima2Eleftherios Pilalis3Constantinos E. Vorgias4Alexandros G. Georgakilas5Aristotelis Chatziioannou6Department of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Zografou Campus, 15701 Athens, GreeceMetabolic Engineering and Bioinformatics Research Team, Institute of Biology Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 11635 Athens, GreeceMetabolic Engineering and Bioinformatics Research Team, Institute of Biology Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 11635 Athens, GreeceEnios Applications Private Limited Company, A17671 Athens, GreeceDepartment of Biochemistry and Molecular Biology, Faculty of Biology, National and Kapodistrian University of Athens, Zografou Campus, 15701 Athens, GreecePhysics Department, School of Applied Mathematical and Physical Sciences, National Technical University of Athens (NTUA), Zografou, 15780 Athens, GreeceMetabolic Engineering and Bioinformatics Research Team, Institute of Biology Medicinal Chemistry & Biotechnology, National Hellenic Research Foundation, 11635 Athens, GreeceIonizing radiation-induced bystander effects (RIBE) encompass a number of effects with potential for a plethora of damages in adjacent non-irradiated tissue. The cascade of molecular events is initiated in response to the exposure to ionizing radiation (IR), something that may occur during diagnostic or therapeutic medical applications. In order to better investigate these complex response mechanisms, we employed a unified framework integrating statistical microarray analysis, signal normalization, and translational bioinformatics functional analysis techniques. This approach was applied to several microarray datasets from Gene Expression Omnibus (GEO) related to RIBE. The analysis produced lists of differentially expressed genes, contrasting bystander and irradiated samples versus sham-irradiated controls. Furthermore, comparative molecular analysis through BioInfoMiner, which integrates advanced statistical enrichment and prioritization methodologies, revealed discrete biological processes, at the cellular level. For example, the negative regulation of growth, cellular response to Zn2+-Cd2+, and Wnt and NIK/NF-kappaB signaling, thus refining the description of the phenotypic landscape of RIBE. Our results provide a more solid understanding of RIBE cell-specific response patterns, especially in the case of high-LET radiations, like α-particles and carbon-ions.https://www.mdpi.com/2072-6694/9/12/160bioinformaticsionizing radiationmicroarraysradiation-induced bystander effectstranscriptomics
spellingShingle Constantinos Yeles
Efstathios-Iason Vlachavas
Olga Papadodima
Eleftherios Pilalis
Constantinos E. Vorgias
Alexandros G. Georgakilas
Aristotelis Chatziioannou
Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
Cancers
bioinformatics
ionizing radiation
microarrays
radiation-induced bystander effects
transcriptomics
title Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
title_full Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
title_fullStr Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
title_full_unstemmed Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
title_short Integrative Bioinformatic Analysis of Transcriptomic Data Identifies Conserved Molecular Pathways Underlying Ionizing Radiation-Induced Bystander Effects (RIBE)
title_sort integrative bioinformatic analysis of transcriptomic data identifies conserved molecular pathways underlying ionizing radiation induced bystander effects ribe
topic bioinformatics
ionizing radiation
microarrays
radiation-induced bystander effects
transcriptomics
url https://www.mdpi.com/2072-6694/9/12/160
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