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Negative selection maintains transcription factor binding motifs in human cancer

Overview of attention for article published in BMC Genomics, June 2016
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  • Good Attention Score compared to outputs of the same age (67th percentile)
  • Good Attention Score compared to outputs of the same age and source (65th percentile)

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Title
Negative selection maintains transcription factor binding motifs in human cancer
Published in
BMC Genomics, June 2016
DOI 10.1186/s12864-016-2728-9
Pubmed ID
Authors

Ilya E. Vorontsov, Grigory Khimulya, Elena N. Lukianova, Daria D. Nikolaeva, Irina A. Eliseeva, Ivan V. Kulakovskiy, Vsevolod J. Makeev

Abstract

Somatic mutations in cancer cells affect various genomic elements disrupting important cell functions. In particular, mutations in DNA binding sites recognized by transcription factors can alter regulator binding affinities and, consequently, expression of target genes. A number of promoter mutations have been linked with an increased risk of cancer. Cancer somatic mutations in binding sites of selected transcription factors have been found under positive selection. However, action and significance of negative selection in non-coding regions remain controversial. Here we present analysis of transcription factor binding motifs co-localized with non-coding variants. To avoid statistical bias we account for mutation signatures of different cancer types. For many transcription factors, including multiple members of FOX, HOX, and NR families, we show that human cancers accumulate fewer mutations than expected by chance that increase or decrease affinity of predicted binding sites. Such stability of binding motifs is even more exhibited in DNase accessible regions. Our data demonstrate negative selection against binding sites alterations and suggest that such selection pressure protects cancer cells from rewiring of regulatory circuits. Further analysis of transcription factors with conserved binding motifs can reveal cell regulatory pathways crucial for the survivability of various human cancers.

X Demographics

X Demographics

The data shown below were collected from the profiles of 6 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 49 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 1 2%
Italy 1 2%
Unknown 47 96%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 8 16%
Student > Bachelor 7 14%
Researcher 7 14%
Student > Master 6 12%
Student > Doctoral Student 3 6%
Other 9 18%
Unknown 9 18%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 14 29%
Agricultural and Biological Sciences 13 27%
Computer Science 7 14%
Medicine and Dentistry 2 4%
Engineering 2 4%
Other 1 2%
Unknown 10 20%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 4. 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 08 July 2016.
All research outputs
#6,919,194
of 22,879,161 outputs
Outputs from BMC Genomics
#3,182
of 10,666 outputs
Outputs of similar age
#113,693
of 352,801 outputs
Outputs of similar age from BMC Genomics
#59
of 174 outputs
Altmetric has tracked 22,879,161 research outputs across all sources so far. This one has received more attention than most of these and is in the 69th percentile.
So far Altmetric has tracked 10,666 research outputs from this source. They receive a mean Attention Score of 4.7. This one has gotten more attention than average, scoring higher than 69% 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 352,801 tracked outputs that were published within six weeks on either side of this one in any source. This one has gotten more attention than average, scoring higher than 67% of its contemporaries.
We're also able to compare this research output to 174 others from the same source and published within six weeks on either side of this one. This one has gotten more attention than average, scoring higher than 65% of its contemporaries.