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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 (85th percentile)
  • Above-average Attention Score compared to outputs of the same age and source (51st percentile)

Mentioned by

22 tweeters
1 video uploader


95 Dimensions

Readers on

175 Mendeley
3 CiteULike
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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

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


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 22 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 175 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Unknown 175 100%

Demographic breakdown

Readers by professional status Count As %
Researcher 45 26%
Student > Ph. D. Student 33 19%
Other 15 9%
Student > Master 15 9%
Student > Bachelor 14 8%
Other 36 21%
Unknown 17 10%
Readers by discipline Count As %
Biochemistry, Genetics and Molecular Biology 65 37%
Medicine and Dentistry 31 18%
Agricultural and Biological Sciences 22 13%
Computer Science 6 3%
Immunology and Microbiology 6 3%
Other 16 9%
Unknown 29 17%

Attention Score in Context

This research output has an Altmetric Attention Score of 13. 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
of 12,576,527 outputs
Outputs from Genome Medicine
of 913 outputs
Outputs of similar age
of 257,320 outputs
Outputs of similar age from Genome Medicine
of 27 outputs
Altmetric has tracked 12,576,527 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 91st percentile: it's in the top 10% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 913 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 22.7. This one has gotten more attention than average, scoring higher than 65% 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 257,320 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 85% of its contemporaries.
We're also able to compare this research output to 27 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 51% of its contemporaries.