Abstract
BackgroundThe growing use of imaging procedures in medicine has raised concerns about exposure to low-dose ionising radiation (LDIR). While the disastrous effects of high dose ionising radiation (HDIR) is well documented, the detrimental effects of LDIR is not well understood and has been a topic of much debate. Since little is known about the effects of LDIR, various kinds of wet-lab and computational analyses are required to advance knowledge in this domain. In this paper we carry out an “upside-down pyramid” form of systems biology analysis of microarray data. We characterised the global genomic response following 10 cGy (low dose) and 100 cGy (high dose) doses of X-ray ionising radiation at four time points by analysing the topology of gene coexpression networks. This study includes a rich experimental design and state-of-the-art computational systems biology methods of analysis to study the differences in the transcriptional response of skin cells exposed to low and high doses of radiation.ResultsUsing this method we found important genes that have been linked to immune response, cell survival and apoptosis. Furthermore, we also were able to identify genes such as BRCA1, ABCA1, TNFRSF1B, MLLT11 that have been associated with various types of cancers. We were also able to detect many genes known to be associated with various medical conditions.ConclusionsOur method of applying network topological differences can aid in identifying the differences among similar (eg: radiation effect) yet very different biological conditions (eg: different dose and time) to generate testable hypotheses. This is the first study where a network level analysis was performed across two different radiation doses at various time points, thereby illustrating changes in the cellular response over time.
Highlights
The growing use of imaging procedures in medicine has raised concerns about exposure to lowdose ionising radiation (LDIR)
We aimed to identify the differences between low dose and high dose ionising radiation contributed to by the genes common to both conditions by studying the gene coexpression network topology
Most studies have analysed the effects of high dose radiation such as atomic bomb survivors in Japan, people exposed during the Chernobyl nuclear accident, patients undergoing radiation therapy, uranium miners, etc
Summary
The growing use of imaging procedures in medicine has raised concerns about exposure to lowdose ionising radiation (LDIR). While the disastrous effects of high dose ionising radiation (HDIR) is well documented, the detrimental effects of LDIR is not well understood and has been a topic of much debate. This study includes a rich experimental design and state-of-the-art computational systems biology methods of analysis to study the differences in the transcriptional response of skin cells exposed to low and high doses of radiation. While occupational related exposure involves low doses of radiation (< 0.5 Gy), therapeutic doses of radiation can be moderate to high (> 1 Gy) Medical procedures, such as diagnostic X-rays, nuclear medicine, and radiation therapy are the most significant source of manmade radiation exposure to the general population. The growing use of imaging procedures has raised concerns about exposure to low-dose ionising radiation (LDIR). With the advancement of high-throughput genomic technologies, global gene (mRNA) expression profiling is one of the latest approaches used to obtain information about the global cellular response to radiation
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