Title |
Mutational signature distribution varies with DNA replication timing and strand asymmetry
|
---|---|
Published in |
Genome Biology, September 2018
|
DOI | 10.1186/s13059-018-1509-y |
Pubmed ID | |
Authors |
Marketa Tomkova, Jakub Tomek, Skirmantas Kriaucionis, Benjamin Schuster-Böckler |
Abstract |
DNA replication plays an important role in mutagenesis, yet little is known about how it interacts with other mutagenic processes. Here, we use somatic mutation signatures-each representing a mutagenic process-derived from 3056 patients spanning 19 cancer types to quantify the strand asymmetry of mutational signatures around replication origins and between early and late replicating regions. We observe that most of the detected mutational signatures are significantly correlated with the timing or direction of DNA replication. The properties of these associations are distinct for different signatures and shed new light on several mutagenic processes. For example, our results suggest that oxidative damage to the nucleotide pool substantially contributes to the mutational landscape of esophageal adenocarcinoma. Together, our results indicate an interaction between DNA replication, the associated damage repair, and most mutagenic processes. |
X Demographics
Geographical breakdown
Country | Count | As % |
---|---|---|
United States | 11 | 29% |
United Kingdom | 11 | 29% |
China | 1 | 3% |
Singapore | 1 | 3% |
Australia | 1 | 3% |
Italy | 1 | 3% |
Israel | 1 | 3% |
Netherlands | 1 | 3% |
Brazil | 1 | 3% |
Other | 0 | 0% |
Unknown | 9 | 24% |
Demographic breakdown
Type | Count | As % |
---|---|---|
Scientists | 19 | 50% |
Members of the public | 17 | 45% |
Science communicators (journalists, bloggers, editors) | 2 | 5% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 136 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 34 | 25% |
Researcher | 24 | 18% |
Student > Bachelor | 17 | 13% |
Student > Master | 12 | 9% |
Other | 7 | 5% |
Other | 14 | 10% |
Unknown | 28 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Biochemistry, Genetics and Molecular Biology | 59 | 43% |
Agricultural and Biological Sciences | 13 | 10% |
Medicine and Dentistry | 10 | 7% |
Computer Science | 6 | 4% |
Mathematics | 3 | 2% |
Other | 14 | 10% |
Unknown | 31 | 23% |