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Achieving high-sensitivity for clinical applications using augmented exome sequencing

Overview of attention for article published in Genome Medicine, July 2015
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  • In the top 25% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (93rd percentile)
  • High Attention Score compared to outputs of the same age and source (87th percentile)

Mentioned by

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45 X users
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1 Redditor

Citations

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47 Dimensions

Readers on

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127 Mendeley
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1 CiteULike
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Title
Achieving high-sensitivity for clinical applications using augmented exome sequencing
Published in
Genome Medicine, July 2015
DOI 10.1186/s13073-015-0197-4
Pubmed ID
Authors

Anil Patwardhan, Jason Harris, Nan Leng, Gabor Bartha, Deanna M. Church, Shujun Luo, Christian Haudenschild, Mark Pratt, Justin Zook, Marc Salit, Jeanie Tirch, Massimo Morra, Stephen Chervitz, Ming Li, Michael Clark, Sarah Garcia, Gemma Chandratillake, Scott Kirk, Euan Ashley, Michael Snyder, Russ Altman, Carlos Bustamante, Atul J. Butte, John West, Richard Chen

Abstract

Whole exome sequencing is increasingly used for the clinical evaluation of genetic disease, yet the variation of coverage and sensitivity over medically relevant parts of the genome remains poorly understood. Several sequencing-based assays continue to provide coverage that is inadequate for clinical assessment. Using sequence data obtained from the NA12878 reference sample and pre-defined lists of medically-relevant protein-coding and noncoding sequences, we compared the breadth and depth of coverage obtained among four commercial exome capture platforms and whole genome sequencing. In addition, we evaluated the performance of an augmented exome strategy, ACE, that extends coverage in medically relevant regions and enhances coverage in areas that are challenging to sequence. Leveraging reference call-sets, we also examined the effects of improved coverage on variant detection sensitivity. We observed coverage shortfalls with each of the conventional exome-capture and whole-genome platforms across several medically interpretable genes. These gaps included areas of the genome required for reporting recently established secondary findings (ACMG) and known disease-associated loci. The augmented exome strategy recovered many of these gaps, resulting in improved coverage in these areas. At clinically-relevant coverage levels (100 % bases covered at ≥20×), ACE improved coverage among genes in the medically interpretable genome (>90 % covered relative to 10-78 % with other platforms), the set of ACMG secondary finding genes (91 % covered relative to 4-75 % with other platforms) and a subset of variants known to be associated with human disease (99 % covered relative to 52-95 % with other platforms). Improved coverage translated into improvements in sensitivity, with ACE variant detection sensitivities (>97.5 % SNVs, >92.5 % InDels) exceeding that observed with conventional whole-exome and whole-genome platforms. Clinicians should consider analytical performance when making clinical assessments, given that even a few missed variants can lead to reporting false negative results. An augmented exome strategy provides a level of coverage not achievable with other platforms, thus addressing concerns regarding the lack of sensitivity in clinically important regions. In clinical applications where comprehensive coverage of medically interpretable areas of the genome requires higher localized sequencing depth, an augmented exome approach offers both cost and performance advantages over other sequencing-based tests.

X Demographics

X Demographics

The data shown below were collected from the profiles of 45 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 127 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 2%
Italy 1 <1%
Brazil 1 <1%
Sweden 1 <1%
Netherlands 1 <1%
United Kingdom 1 <1%
South Africa 1 <1%
Spain 1 <1%
Canada 1 <1%
Other 0 0%
Unknown 117 92%

Demographic breakdown

Readers by professional status Count As %
Researcher 40 31%
Student > Ph. D. Student 25 20%
Other 19 15%
Professor 7 6%
Student > Master 7 6%
Other 15 12%
Unknown 14 11%
Readers by discipline Count As %
Agricultural and Biological Sciences 46 36%
Biochemistry, Genetics and Molecular Biology 34 27%
Medicine and Dentistry 12 9%
Computer Science 5 4%
Engineering 4 3%
Other 7 6%
Unknown 19 15%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 26. 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 16 March 2020.
All research outputs
#1,454,185
of 25,390,970 outputs
Outputs from Genome Medicine
#311
of 1,584 outputs
Outputs of similar age
#17,922
of 276,796 outputs
Outputs of similar age from Genome Medicine
#6
of 40 outputs
Altmetric has tracked 25,390,970 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 94th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,584 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 26.8. This one has done well, scoring higher than 80% 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 276,796 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 93% of its contemporaries.
We're also able to compare this research output to 40 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 87% of its contemporaries.