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APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication

Overview of attention for article published in Genome Research, January 2016
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  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (98th percentile)
  • High Attention Score compared to outputs of the same age and source (85th percentile)

Mentioned by

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13 news outlets
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14 X users
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2 Facebook pages

Citations

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154 Dimensions

Readers on

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196 Mendeley
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5 CiteULike
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Title
APOBEC-induced mutations in human cancers are strongly enriched on the lagging DNA strand during replication
Published in
Genome Research, January 2016
DOI 10.1101/gr.197046.115
Pubmed ID
Authors

Vladimir B. Seplyarskiy, Ruslan A. Soldatov, Konstantin Y. Popadin, Stylianos E. Antonarakis, Georgii A. Bazykin, Sergey I. Nikolaev

Abstract

APOBEC3A and APOBEC3B, cytidine deaminases of the APOBEC family, are among the main factors causing mutations in human cancers. APOBEC deaminates cytosines in single-stranded DNA (ssDNA). A fraction of the APOBEC-induced mutations occur as clusters ("kataegis") in single-stranded DNA produced during repair of double-stranded breaks (DSBs). However, the properties of the remaining 87% of nonclustered APOBEC-induced mutations, the source and the genomic distribution of the ssDNA where they occur, are largely unknown. By analyzing genomic and exomic cancer databases, we show that >33% of dispersed APOBEC-induced mutations occur on the lagging strand during DNA replication, thus unraveling the major source of ssDNA targeted by APOBEC in cancer. Although methylated cytosine is generally more mutation-prone than nonmethylated cytosine, we report that methylation reduces the rate of APOBEC-induced mutations by a factor of roughly two. Finally, we show that in cancers with extensive APOBEC-induced mutagenesis, there is almost no increase in mutation rates in late replicating regions (contrary to other cancers). Because late-replicating regions are depleted in exons, this results in a 1.3-fold higher fraction of mutations residing within exons in such cancers. This study provides novel insight into the APOBEC-induced mutagenesis and describes the peculiarity of the mutational processes in cancers with the signature of APOBEC-induced mutations.

X Demographics

X Demographics

The data shown below were collected from the profiles of 14 X users who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 196 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 <1%
Russia 1 <1%
Poland 1 <1%
Unknown 193 98%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 42 21%
Researcher 39 20%
Student > Master 21 11%
Student > Bachelor 19 10%
Professor > Associate Professor 8 4%
Other 23 12%
Unknown 44 22%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 61 31%
Agricultural and Biological Sciences 37 19%
Medicine and Dentistry 21 11%
Computer Science 6 3%
Immunology and Microbiology 5 3%
Other 17 9%
Unknown 49 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 113. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 05 October 2022.
All research outputs
#352,254
of 24,570,543 outputs
Outputs from Genome Research
#74
of 4,366 outputs
Outputs of similar age
#6,318
of 405,181 outputs
Outputs of similar age from Genome Research
#6
of 35 outputs
Altmetric has tracked 24,570,543 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 98th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,366 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 17.3. This one has done particularly well, scoring higher than 98% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 405,181 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 98% of its contemporaries.
We're also able to compare this research output to 35 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 85% of its contemporaries.