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Lessons learned from additional research analyses of unsolved clinical exome cases

Overview of attention for article published in Genome Medicine, March 2017
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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 (84th percentile)
  • Good Attention Score compared to outputs of the same age and source (66th percentile)

Mentioned by

twitter
21 tweeters
video
1 video uploader

Citations

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156 Dimensions

Readers on

mendeley
221 Mendeley
citeulike
3 CiteULike
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Title
Lessons learned from additional research analyses of unsolved clinical exome cases
Published in
Genome Medicine, March 2017
DOI 10.1186/s13073-017-0412-6
Pubmed ID
Authors

Mohammad K. Eldomery, Zeynep Coban-Akdemir, Tamar Harel, Jill A. Rosenfeld, Tomasz Gambin, Asbjørg Stray-Pedersen, Sébastien Küry, Sandra Mercier, Davor Lessel, Jonas Denecke, Wojciech Wiszniewski, Samantha Penney, Pengfei Liu, Weimin Bi, Seema R. Lalani, Christian P. Schaaf, Michael F. Wangler, Carlos A. Bacino, Richard Alan Lewis, Lorraine Potocki, Brett H. Graham, John W. Belmont, Fernando Scaglia, Jordan S. Orange, Shalini N. Jhangiani, Theodore Chiang, Harsha Doddapaneni, Jianhong Hu, Donna M. Muzny, Fan Xia, Arthur L. Beaudet, Eric Boerwinkle, Christine M. Eng, Sharon E. Plon, V. Reid Sutton, Richard A. Gibbs, Jennifer E. Posey, Yaping Yang, James R. Lupski

Abstract

Given the rarity of most single-gene Mendelian disorders, concerted efforts of data exchange between clinical and scientific communities are critical to optimize molecular diagnosis and novel disease gene discovery. We designed and implemented protocols for the study of cases for which a plausible molecular diagnosis was not achieved in a clinical genomics diagnostic laboratory (i.e. unsolved clinical exomes). Such cases were recruited to a research laboratory for further analyses, in order to potentially: (1) accelerate novel disease gene discovery; (2) increase the molecular diagnostic yield of whole exome sequencing (WES); and (3) gain insight into the genetic mechanisms of disease. Pilot project data included 74 families, consisting mostly of parent-offspring trios. Analyses performed on a research basis employed both WES from additional family members and complementary bioinformatics approaches and protocols. Analysis of all possible modes of Mendelian inheritance, focusing on both single nucleotide variants (SNV) and copy number variant (CNV) alleles, yielded a likely contributory variant in 36% (27/74) of cases. If one includes candidate genes with variants identified within a single family, a potential contributory variant was identified in a total of ~51% (38/74) of cases enrolled in this pilot study. The molecular diagnosis was achieved in 30/63 trios (47.6%). Besides this, the analysis workflow yielded evidence for pathogenic variants in disease-associated genes in 4/6 singleton cases (66.6%), 1/1 multiplex family involving three affected siblings, and 3/4 (75%) quartet families. Both the analytical pipeline and the collaborative efforts between the diagnostic and research laboratories provided insights that allowed recent disease gene discoveries (PURA, TANGO2, EMC1, GNB5, ATAD3A, and MIPEP) and increased the number of novel genes, defined in this study as genes identified in more than one family (DHX30 and EBF3). An efficient genomics pipeline in which clinical sequencing in a diagnostic laboratory is followed by the detailed reanalysis of unsolved cases in a research environment, supplemented with WES data from additional family members, and subject to adjuvant bioinformatics analyses including relaxed variant filtering parameters in informatics pipelines, can enhance the molecular diagnostic yield and provide mechanistic insights into Mendelian disorders. Implementing these approaches requires collaborative clinical molecular diagnostic and research efforts.

Twitter Demographics

The data shown below were collected from the profiles of 21 tweeters who shared this research output. Click here to find out more about how the information was compiled.

Mendeley readers

The data shown below were compiled from readership statistics for 221 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 221 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 56 25%
Student > Ph. D. Student 40 18%
Student > Master 23 10%
Other 16 7%
Student > Doctoral Student 15 7%
Other 44 20%
Unknown 27 12%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 84 38%
Medicine and Dentistry 38 17%
Agricultural and Biological Sciences 24 11%
Neuroscience 10 5%
Immunology and Microbiology 6 3%
Other 21 10%
Unknown 38 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 14. 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 28 February 2018.
All research outputs
#2,151,689
of 21,815,602 outputs
Outputs from Genome Medicine
#507
of 1,385 outputs
Outputs of similar age
#42,672
of 284,669 outputs
Outputs of similar age from Genome Medicine
#3
of 6 outputs
Altmetric has tracked 21,815,602 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 90th percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 1,385 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 25.4. This one has gotten more attention than average, scoring higher than 63% 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 284,669 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 84% of its contemporaries.
We're also able to compare this research output to 6 others from the same source and published within six weeks on either side of this one. This one has scored higher than 3 of them.