PMID- 32821428
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210715
IS  - 2056-7944 (Electronic)
IS  - 2056-7944 (Linking)
VI  - 5
DP  - 2020
TI  - Partially automated whole-genome sequencing reanalysis of previously undiagnosed 
      pediatric patients can efficiently yield new diagnoses.
PG  - 33
LID - 10.1038/s41525-020-00140-1 [doi]
LID - 33
AB  - To investigate the diagnostic and clinical utility of a partially automated 
      reanalysis pipeline, forty-eight cases of seriously ill children with suspected 
      genetic disease who did not receive a diagnosis upon initial manual analysis of 
      whole-genome sequencing (WGS) were reanalyzed at least 1 year later. Clinical 
      natural language processing (CNLP) of medical records provided automated, updated 
      patient phenotypes, and an automated analysis system delivered limited lists of 
      possible diagnostic variants for each case. CNLP identified a median of 79 new 
      clinical features per patient at least 1 year later. Compared to a standard 
      manual reanalysis pipeline, the partially automated pipeline reduced the number 
      of variants to be analyzed by 90% (range: 74%-96%). In 2 cases, diagnoses were 
      made upon reinterpretation, representing an incremental diagnostic yield of 4.2% 
      (2/48, 95% CI: 0.5-14.3%). Four additional cases were flagged with a possible 
      diagnosis to be considered during subsequent reanalysis. Separately, copy number 
      analysis led to diagnoses in two cases. Ongoing discovery of new disease genes 
      and refined variant classification necessitate periodic reanalysis of negative 
      WGS cases. The clinical features of patients sequenced as infants evolve rapidly 
      with age. Partially automated reanalysis, including automated re-phenotyping 
      through CNLP, has the potential to identify molecular diagnoses with reduced 
      expert labor intensity.
CI  - (c) The Author(s) 2020.
FAU - James, Kiely N
AU  - James KN
AUID- ORCID: 0000-0001-8409-4363
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Clark, Michelle M
AU  - Clark MM
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Camp, Brandon
AU  - Camp B
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Kint, Cyrielle
AU  - Kint C
AD  - Diploid, Leuven, Belgium.
FAU - Schols, Peter
AU  - Schols P
AD  - Diploid, Leuven, Belgium.
FAU - Batalov, Sergey
AU  - Batalov S
AUID- ORCID: 0000-0002-0925-0554
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Briggs, Benjamin
AU  - Briggs B
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Veeraraghavan, Narayanan
AU  - Veeraraghavan N
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Chowdhury, Shimul
AU  - Chowdhury S
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
FAU - Kingsmore, Stephen F
AU  - Kingsmore SF
AD  - Rady Children's Institute for Genomic Medicine, San Diego, CA USA. GRID: 
      grid.286440.c. ISNI: 0000 0004 0383 2910
LA  - eng
GR  - U19 HD077693/HD/NICHD NIH HHS/United States
PT  - Journal Article
DEP - 20200811
PL  - England
TA  - NPJ Genom Med
JT  - NPJ genomic medicine
JID - 101685193
PMC - PMC7419288
OTO - NOTNLM
OT  - Genetic testing
OT  - Molecular medicine
COIS- Competing interestsC.K. and P.S. are employees of Diploid, acquired by Invitae 
      (San Francisco, CA) in 2020. K.N.J., M.M.C., B.C., S.B., B.B., N.V., S.C., and 
      S.F.K. declare that there are no competing interests.
EDAT- 2020/08/22 06:00
MHDA- 2020/08/22 06:01
PMCR- 2020/08/11
CRDT- 2020/08/22 06:00
PHST- 2020/02/13 00:00 [received]
PHST- 2020/07/14 00:00 [accepted]
PHST- 2020/08/22 06:00 [entrez]
PHST- 2020/08/22 06:00 [pubmed]
PHST- 2020/08/22 06:01 [medline]
PHST- 2020/08/11 00:00 [pmc-release]
AID - 140 [pii]
AID - 10.1038/s41525-020-00140-1 [doi]
PST - epublish
SO  - NPJ Genom Med. 2020 Aug 11;5:33. doi: 10.1038/s41525-020-00140-1. eCollection 
      2020.