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.
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.|Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Ellina
authors.initials: E
authors.lastname: Macaeva
authors.affiliation: Data Mining and Modelling for Biomedicine Group, VIB Inflammation Research Center, Zwijnaarde, Belgium.|Department of Respiratory Medicine, Ghent University, Ghent, Belgium.
authors.forename: Yvan
authors.initials: Y
authors.lastname: Saeys
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Kevin
authors.initials: K
authors.lastname: Tabury
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Ann
authors.initials: A
authors.lastname: Janssen
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Arlette
authors.initials: A
authors.lastname: Michaux
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Mohammed A
authors.initials: MA
authors.lastname: Benotmane
authors.affiliation: Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.|Department of Veterinary Sciences, University of Antwerp, Antwerp, Belgium.
authors.forename: Winnok H
authors.initials: WH
authors.lastname: De Vos
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.|Department of Molecular Biotechnology, Ghent University, Ghent, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Baatout
authors.affiliation: Radiobiology Unit, Belgian Nuclear Research Centre, SCK•CEN, Mol, Belgium.
authors.forename: Roel
authors.initials: R
authors.lastname: Quintens
mesh_terms: D000328:Adult; D015415:Biomarkers; D016000:Cluster Analysis; D004307:Dose-Response Relationship, Radiation; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000528:radiation effects; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000528:radiation effects; D008297:Male; D008875:Middle Aged; D012326:RNA Splicing / Q000528:radiation effects*; D011827:Radiation; D011874:Radiometry; D015203:Reproducibility of Results; D014158:Transcription, Genetic / Q000528:radiation effects*; D059467:Transcriptome; D014965:X-Rays; D055815:Young Adult
chemical_list: D015415:Biomarkers