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Biased estimates of clonal evolution and subclonal heterogeneity can arise from PCR duplicates in deep sequencing experiments

Overview of attention for article published in Genome Biology, August 2014
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About this Attention Score

  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (87th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (62nd percentile)

Mentioned by

blogs
1 blog
twitter
7 X users

Citations

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33 Dimensions

Readers on

mendeley
123 Mendeley
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3 CiteULike
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Title
Biased estimates of clonal evolution and subclonal heterogeneity can arise from PCR duplicates in deep sequencing experiments
Published in
Genome Biology, August 2014
DOI 10.1186/s13059-014-0420-4
Pubmed ID
Authors

Erin N Smith, Kristen Jepsen, Mahdieh Khosroheidari, Laura Z Rassenti, Matteo D’Antonio, Emanuela M Ghia, Dennis A Carson, Catriona HM Jamieson, Thomas J Kipps, Kelly A Frazer

Abstract

Accurate allele frequencies are important for measuring subclonal heterogeneity and clonal evolution. Deep-targeted sequencing data can contain PCR duplicates, inflating perceived read depth. Here we adapted the Illumina TruSeq Custom Amplicon kit to include single molecule tagging (SMT) and show that SMT-identified duplicates arise from PCR. We demonstrate that retention of PCR duplicate reads can imply clonal evolution when none exists, while their removal effectively controls the false positive rate. Additionally, PCR duplicates alter estimates of subclonal heterogeneity in tumor samples. Our method simplifies PCR duplicate identification and emphasizes their removal in studies of tumor heterogeneity and clonal evolution.

X Demographics

X Demographics

The data shown below were collected from the profiles of 7 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 123 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 4 3%
United States 4 3%
Sweden 1 <1%
Canada 1 <1%
Unknown 113 92%

Demographic breakdown

Readers by professional status Count As %
Student > Ph. D. Student 35 28%
Researcher 34 28%
Student > Master 8 7%
Student > Doctoral Student 6 5%
Student > Bachelor 6 5%
Other 20 16%
Unknown 14 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 53 43%
Biochemistry, Genetics and Molecular Biology 26 21%
Medicine and Dentistry 10 8%
Computer Science 9 7%
Neuroscience 2 2%
Other 7 6%
Unknown 16 13%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 12. 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 26 August 2014.
All research outputs
#3,001,931
of 25,373,627 outputs
Outputs from Genome Biology
#2,253
of 4,467 outputs
Outputs of similar age
#29,247
of 241,594 outputs
Outputs of similar age from Genome Biology
#33
of 87 outputs
Altmetric has tracked 25,373,627 research outputs across all sources so far. Compared to these this one has done well and is in the 88th percentile: it's in the top 25% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 4,467 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 27.6. This one is in the 49th percentile – i.e., 49% of its peers scored the same or lower than it.
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 241,594 tracked outputs that were published within six weeks on either side of this one in any source. This one has done well, scoring higher than 87% of its contemporaries.
We're also able to compare this research output to 87 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 62% of its contemporaries.