Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry

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@article{e6143cdc7ecf4078b5639f75bb0f713b,
title = "Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry",
abstract = "Accurate assessment of the individual exposure dose based on easily accessible samples (e.g. blood) immediately following a radiological accident is crucial. We aimed at developing a robust transcription-based signature for biodosimetry from human peripheral blood mononuclear cells irradiated with different doses of X-rays (0.1 and 1.0 Gy) at a dose rate of 0.26 Gy/min. Genome-wide radiation-induced changes in mRNA expression were evaluated at both gene and exon level. Using exon-specific qRT-PCR, we confirmed that several biomarker genes are alternatively spliced or transcribed after irradiation and that different exons of these genes exhibit significantly different levels of induction. Moreover, a significant number of radiation-responsive genes were found to be genomic neighbors. Using three different classification models we found that gene and exon signatures performed equally well on dose prediction, as long as more than 10 features are included. Together, our results highlight the necessity of evaluating gene expression at the level of single exons for radiation biodosimetry in particular and transcriptional biomarker research in general. This approach is especially advisable for practical gene expression-based biodosimetry, for which primer- or probe-based techniques would be the method of choice.",
keywords = "ionizing radiation, biomarkers, alternative transcription/splicing, gene signatures, exon signatures",
author = "Ellina Macaeva and Yvan Saeys and Kevin Tabury and Ann Janssen and Arlette Michaux and Rafi Benotmane and {De Vos}, {Winnok H.} and Sarah Baatout and Roel Quintens",
note = "Score=10",
year = "2016",
month = "1",
day = "14",
doi = "10.1038/srep19251",
language = "English",
volume = "6",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",

}

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TY - JOUR

T1 - Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry

AU - Macaeva, Ellina

AU - Saeys, Yvan

AU - Tabury, Kevin

AU - Janssen, Ann

AU - Michaux, Arlette

AU - Benotmane, Rafi

AU - De Vos, Winnok H.

AU - Baatout, Sarah

AU - Quintens, Roel

N1 - Score=10

PY - 2016/1/14

Y1 - 2016/1/14

N2 - Accurate assessment of the individual exposure dose based on easily accessible samples (e.g. blood) immediately following a radiological accident is crucial. We aimed at developing a robust transcription-based signature for biodosimetry from human peripheral blood mononuclear cells irradiated with different doses of X-rays (0.1 and 1.0 Gy) at a dose rate of 0.26 Gy/min. Genome-wide radiation-induced changes in mRNA expression were evaluated at both gene and exon level. Using exon-specific qRT-PCR, we confirmed that several biomarker genes are alternatively spliced or transcribed after irradiation and that different exons of these genes exhibit significantly different levels of induction. Moreover, a significant number of radiation-responsive genes were found to be genomic neighbors. Using three different classification models we found that gene and exon signatures performed equally well on dose prediction, as long as more than 10 features are included. Together, our results highlight the necessity of evaluating gene expression at the level of single exons for radiation biodosimetry in particular and transcriptional biomarker research in general. This approach is especially advisable for practical gene expression-based biodosimetry, for which primer- or probe-based techniques would be the method of choice.

AB - Accurate assessment of the individual exposure dose based on easily accessible samples (e.g. blood) immediately following a radiological accident is crucial. We aimed at developing a robust transcription-based signature for biodosimetry from human peripheral blood mononuclear cells irradiated with different doses of X-rays (0.1 and 1.0 Gy) at a dose rate of 0.26 Gy/min. Genome-wide radiation-induced changes in mRNA expression were evaluated at both gene and exon level. Using exon-specific qRT-PCR, we confirmed that several biomarker genes are alternatively spliced or transcribed after irradiation and that different exons of these genes exhibit significantly different levels of induction. Moreover, a significant number of radiation-responsive genes were found to be genomic neighbors. Using three different classification models we found that gene and exon signatures performed equally well on dose prediction, as long as more than 10 features are included. Together, our results highlight the necessity of evaluating gene expression at the level of single exons for radiation biodosimetry in particular and transcriptional biomarker research in general. This approach is especially advisable for practical gene expression-based biodosimetry, for which primer- or probe-based techniques would be the method of choice.

KW - ionizing radiation

KW - biomarkers

KW - alternative transcription/splicing

KW - gene signatures

KW - exon signatures

UR - http://www.nature.com/articles/srep19251

UR - http://ecm.sckcen.be/OTCS/llisapi.dll?func=ll&objaction=overview&objid=12804183

U2 - 10.1038/srep19251

DO - 10.1038/srep19251

M3 - Article

VL - 6

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

M1 - 19251

ER -

ID: 609192