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Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry.
- Source :
-
Scientific reports [Sci Rep] 2016 Jan 14; Vol. 6, pp. 19251. Date of Electronic Publication: 2016 Jan 14. - Publication Year :
- 2016
-
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.
- Subjects :
- Adult
Biomarkers
Cluster Analysis
Dose-Response Relationship, Radiation
Female
Gene Expression Profiling
Gene Expression Regulation radiation effects
Humans
Leukocytes, Mononuclear metabolism
Leukocytes, Mononuclear radiation effects
Male
Middle Aged
Reproducibility of Results
Transcriptome
X-Rays
Young Adult
RNA Splicing radiation effects
Radiation
Radiometry
Transcription, Genetic radiation effects
Subjects
Details
- Language :
- English
- ISSN :
- 2045-2322
- Volume :
- 6
- Database :
- MEDLINE
- Journal :
- Scientific reports
- Publication Type :
- Academic Journal
- Accession number :
- 26763932
- Full Text :
- https://doi.org/10.1038/srep19251