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

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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
BLOOD-CELLS, IONIZING-RADIATION, ARRAY DATA, EX-VIVO, IDENTIFICATION, PREDICTION, BIOMARKERS, RADIOTHERAPY PATIENTS, ACCIDENT MEDICAL-MANAGEMENT, GENE-EXPRESSION SIGNATURES

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Chicago
Macaeva, Ellina, Yvan Saeys, Kevin Tabury, Ann Janssen, Arlette Michaux, Mohammed A Benotmane, Winnok De Vos, Sarah Baatout, and Roel Quintens. 2016. “Radiation-induced Alternative Transcription and Splicing Events and Their Applicability to Practical Biodosimetry.” Scientific Reports 6.
APA
Macaeva, E., Saeys, Y., Tabury, K., Janssen, A., Michaux, A., Benotmane, M. A., De Vos, W., et al. (2016). Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry. SCIENTIFIC REPORTS, 6.
Vancouver
1.
Macaeva E, Saeys Y, Tabury K, Janssen A, Michaux A, Benotmane MA, et al. Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry. SCIENTIFIC REPORTS. 2016;6.
MLA
Macaeva, Ellina, Yvan Saeys, Kevin Tabury, et al. “Radiation-induced Alternative Transcription and Splicing Events and Their Applicability to Practical Biodosimetry.” SCIENTIFIC REPORTS 6 (2016): n. pag. Print.
@article{7073590,
  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.},
  articleno    = {19251},
  author       = {Macaeva, Ellina and Saeys, Yvan and Tabury, Kevin and Janssen, Ann and Michaux, Arlette and Benotmane, Mohammed A and De Vos, Winnok and Baatout, Sarah and Quintens, Roel},
  issn         = {2045-2322},
  journal      = {SCIENTIFIC REPORTS},
  language     = {eng},
  pages        = {13},
  title        = {Radiation-induced alternative transcription and splicing events and their applicability to practical biodosimetry},
  url          = {http://dx.doi.org/10.1038/srep19251},
  volume       = {6},
  year         = {2016},
}

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