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Partially automated whole-genome sequencing reanalysis of previously undiagnosed pediatric patients can efficiently yield new diagnoses.

ABSTRACT: 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.

SUBMITTER: James KN

PROVIDER: S-EPMC7419288 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Partially automated whole-genome sequencing reanalysis of previously undiagnosed pediatric patients can efficiently yield new diagnoses.

James Kiely N KN Clark Michelle M MM Camp Brandon B Kint Cyrielle C Schols Peter P Batalov Sergey S Briggs Benjamin B Veeraraghavan Narayanan N Chowdhury Shimul S Kingsmore Stephen F SF

NPJ genomic medicine 20200811

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 vari ...[more]

PMID: 32821428

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Project description:Because osteoporosis is under-recognized in patients with vertebral fractures, we evaluated characteristics associated with osteoporosis identification. Most patients with vertebral fractures did not receive evaluation or treatment for osteoporosis. Black, younger, and male participants were particularly unlikely to have had recognized osteoporosis, which could increase their risk of negative outcomes.IntroductionVertebral fractures may be identified on imaging but fail to prompt evaluation for osteoporosis. Our objective was to evaluate characteristics associated with clinical osteoporosis recognition in patients who had vertebral fractures detected on their thoracolumbar spine imaging reports.MethodsWe prospectively identified individuals who received imaging of the lower spine at primary care clinics in 4 large healthcare systems who were eligible for osteoporosis screening and lacked indications of osteoporosis diagnoses or treatments in the prior year. We evaluated characteristics of participants with identified vertebral fractures that were associated with recognition of osteoporosis (diagnosis code in the health record; receipt of bone mineral density scans; and/or prescriptions for anti-osteoporotic medications). We used mixed models to estimate adjusted odds ratios (ORs) and 95% confidence intervals (95% CIs).ResultsA total of 114,005 participants (47% female; mean age 65 (interquartile range: 57-72) years) were evaluated. Of the 8579 (7%) participants with vertebral fractures identified, 3784 (44%) had recognition of osteoporosis within the subsequent year. In adjusted regressions, Black participants (OR (95% CI): 0.74 (0.57, 0.97)), younger participants (age 50-60: 0.48 (0.42, 0.54); age 61-64: 0.70 (0.60, 0.81)), and males (0.39 (0.35, 0.43)) were less likely to have recognized osteoporosis compared to white participants, adults aged 65 + years, or females.ConclusionIndividuals with identified vertebral fractures commonly did not have recognition of osteoporosis within a year, particularly those who were younger, Black, or male. Providers and healthcare systems should consider efforts to improve evaluation of osteoporosis in patients with vertebral fractures.

Dataset Information

Partially automated whole-genome sequencing reanalysis of previously undiagnosed pediatric patients can efficiently yield new diagnoses.

Publications

Partially automated whole-genome sequencing reanalysis of previously undiagnosed pediatric patients can efficiently yield new diagnoses.

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