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. 2019 Jun 20;380(25):2478-2480.
doi: 10.1056/NEJMc1812033.

Reanalysis of Clinical Exome Sequencing Data

Pengfei Liu  1 , Linyan Meng  1 , Elizabeth A Normand  1 , Fan Xia  1 , Xiaofei Song  1 , Andrew Ghazi  1 , Jill Rosenfeld  1 , Pilar L Magoulas  1 , Alicia Braxton  1 , Patricia Ward  1 , Hongzheng Dai  1 , Bo Yuan  1 , Weimin Bi  1 , Rui Xiao  1 , Xia Wang  1 , Theodore Chiang  1 , Francesco Vetrini  2 , Weimin He  2 , Hanyin Cheng  2 , Jie Dong  2 , Charul Gijavanekar  2 , Paul J Benke  3 , Jonathan A Bernstein  4 , Tanya Eble  1 , Yasemen Eroglu  5 , Deanna Erwin  1 , Luis Escobar  6 , James B Gibson  7 , Karen Gripp  8 , Soledad Kleppe  9 , Mary K Koenig  10 , Andrea M Lewis  1 , Marvin Natowicz  11 , Pedro Mancias  10 , LaKeesha Minor  10 , Fernando Scaglia  1 , Christian P Schaaf  12 , Haley Streff  1 , Hilary Vernon  13 , Crescenda L Uhles  14 , Elaine H Zackai  15 , Nan Wu  16 , V Reid Sutton  1 , Arthur L Beaudet  1 , Donna Muzny  1 , Richard A Gibbs  1 , Jennifer E Posey  1 , Seema Lalani  1 , Chad Shaw  1 , Christine M Eng  1 , James R Lupski  1 , Yaping Yang  1
Affiliations

Reanalysis of Clinical Exome Sequencing Data

Pengfei Liu et al. N Engl J Med. .
No abstract available

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Figures

Figure 1.
Figure 1.. Systematic reanalysis increases diagnostic rates in two patient series referred to clinical exome sequencing.
The left (Cohort #1, N=250) and the right (Cohort #2, N=2000) panels depict the molecular diagnostic rate changes from the original rates, evidenced by respective publications,, and the reanalysis rates. The yield alteration originates from patients whose diagnostic molecular findings changed from zero to one or more (new diagnosis, highlighted in red in the reanalysis bar), from one to two or more (multilocus pathogenic variation; the white segment below the red segment in the reanalysis bar), and from one to zero (overturned molecular diagnosis, see Supplemental Appendix). The white segment above the red segment represents the proportion of patients who received a partial diagnosis from reanalysis (n=2 for Cohort #1, n=5 for Cohort #2), which is not counted towards the diagnostic rate. The Pareto charts to the right of the bar charts illustrate the breakdown of the interpretive reasons contributing to each new molecular diagnosis, with cumulative counts from each category shown in the bottom axis and the cumulative percentages shown in the top axis.
See this image and copyright information in PMC

References

    1. Wenger AM, Guturu H, Bernstein JA, Bejerano G. Systematic reanalysis of clinical exome data yields additional diagnoses: implications for providers. Genet Med 2017;19:209–14. - PubMed
    1. Eldomery MK, Coban-Akdemir Z, Harel T, et al. Lessons learned from additional research analyses of unsolved clinical exome cases. Genome Med 2017;9:26. - PMC - PubMed
    1. Yang Y, Muzny DM, Reid JG, et al. Clinical whole-exome sequencing for the diagnosis of mendelian disorders. N Engl J Med 2013;369:1502–11. - PMC - PubMed
    1. Yang Y, Muzny DM, Xia F, et al. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 2014;312:1870–9. - PMC - PubMed
    1. Posey JE, Harel T, Liu P, et al. Resolution of Disease Phenotypes Resulting from Multilocus Genomic Variation. N Engl J Med 2017;376:21–31. - PMC - PubMed