Feasibility of Ultra-Rapid Exome Sequencing in Critically Ill Infants and Children With Suspected Monogenic Conditions in the Australian Public Health Care System
Open accessAbstract
Importance: Widespread adoption of rapid genomic testing in pediatric critical care requires robust clinical and laboratory pathways that provide equitable and consistent service across health care systems. Objective: To prospectively evaluate the performance of a multicenter network for ultra-rapid genomic diagnosis in a public health care system. Design, Setting, and Participants: Descriptive feasibility study of critically ill pediatric patients with suspected monogenic conditions treated at 12 Australian hospitals between March 2018 and February 2019, with data collected to May 2019. A formal implementation strategy emphasizing communication and feedback, standardized processes, coordination, distributed leadership, and collective learning was used to facilitate adoption. Exposures: Ultra-rapid exome sequencing. Main Outcomes and Measures: The primary outcome was time from sample receipt to ultra-rapid exome sequencing report. The secondary outcomes were the molecular diagnostic yield, the change in clinical management after the ultra-rapid exome sequencing report, the time from hospital admission to the laboratory report, and the proportion of laboratory reports returned prior to death or hospital discharge. Results: The study population included 108 patients with a median age of 28 days (range, 0 days to 17 years); 34% were female; and 57% were from neonatal intensive care units, 33% were from pediatric intensive care units, and 9% were from other hospital wards. The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days) and the median time was 3 days (range, 2-7 days). The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days) and 93 reports (86%) were issued prior to death or hospital discharge. A molecular diagnosis was established in 55 patients (51%). Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis. In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management. Targeted treatments were initiated in 12 patients (11%), treatment was redirected toward palliative care in 14 patients (13%), and surveillance for specific complications was initiated in 19 patients (18%). Conclusions and Relevance: This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system. However, further research is needed to understand the clinical value of such testing, and the generalizability of the findings to other health care settings.
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- Findingown data
The study enrolled 108 patients.
“The study population included 108 patients”
Quote in the paperNot a substantial claim - Findingown data
Surveillance for specific complications was started in 19 patients (18%).
“surveillance for specific complications was initiated in 19 patients (18%)”
- Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
“including targeted surveillance to identify complications of the condition in 19 patients (18%)”
Quote in the paperNot a substantial claim - Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
- Findingown data
One patient with pontocerebellar hypoplasia had an unbalanced translocation found on concurrent chromosomal microarray and was excluded from the ultra-rapid exome sequencing diagnostic yield.
“One patient with pontocerebellar hypoplasia was found to have an unbalanced translocation on concurrent chromosomal microarray, and was not included in the ultra-rapid exome sequencing diagnostic”
Quote in the paperNot a substantial claim - Findingown data
Among the 53 patients without a molecular diagnosis, 6 (11%) had their clinical management considered influenced by the ultra-rapid exome sequencing result.
“In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management.”
- Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
“Among the 53 patients who did not receive a molecular diagnosis through ultra-rapid exome sequencing, 6 (11%) were considered as having had a change in clinical management”
Quote in the paperSubstantial claim - Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
- Findingown data
Ninety-three reports (86%) were issued before death or hospital discharge.
“93 reports (86%) were issued prior to death or hospital discharge”
Quote in the paperSubstantial claim
- Findingown data
Treatment was redirected toward palliative care in 14 patients (13%).
“treatment was redirected toward palliative care in 14 patients (13%)”
Quote in the paperNot a substantial claim - Findingown data
Among 3 of the 10 patients from other hospital wards, the molecular diagnostic yield was 30% (95% CI, 0%-50%).
“Among 3 of the 10 patients enrolled from other hospi- tal wards, the molecular diagnostic yield was 30% (95% CI, 0%-50%).”
Quote in the paperNot a substantial claim - Findingown data
Among the 55 patients with a molecular diagnosis, 42 (76%) had their clinical management considered influenced by the ultra-rapid exome sequencing result.
“In 42 of 55 patients (76%) with a molecular diagnosis and 6 of 53 patients (11%) without a molecular diagnosis, the ultra-rapid exome sequencing result was considered as having influenced clinical management.”
- Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
“Among the 55 patients receiving a molecular diagnosis, 42 (76%) were considered as having had a subsequent change in clinical management”
Quote in the paperSubstantial claim - Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
- Findingown data
Among 17 of the 36 PICU patients, the molecular diagnostic yield was 47.0% (95% CI, 27.8%-66.1%).
“Among 17 of the 36 patients enrolled from the PICU, the molecular diagnostic yield was 47.0% (95% CI, 27.8%-66.1%).”
Quote in the paperSubstantial claim - Findingown data
Eleven molecular diagnoses (20% of all diagnoses) came from extended approaches beyond standard exome analysis, including mitochondrial genome sequencing, exome-based copy number analysis, international database matching for novel gene-disease associations, additional phenotyping, and RNA analysis.
“Eleven diagnoses (20%) resulted from using the following approaches to augment standard exome sequencing analysis: mitochondrial genome sequencing analysis, exome sequencing-based copy number analysis, use of international databases to identify novel gene-disease associations, and additional phenotyping and RNA analysis.”
- Also stated in: § Discussion · plain
“Twenty percent of the molecular diagnoses were made using approaches that extend usual clinical exome sequencing diagnostic practice, including mitochondrial genome sequencing, identification of single-gene copy number variants from exome sequencing data, real-time use of international databases to establish novel gene-disease associations, RNA studies, and additional phenotyping.”
Quote in the paperSubstantial claim - Also stated in: § Discussion · plain
- Findingown data
The mean time from hospital admission to the ultra-rapid exome sequencing report was 17.5 days, with a 95% CI of 14.6 to 21.1 days.
“The mean time from hospital admission to ultra-rapid exome sequencing report was 17.5 days (95% CI, 14.6-21.1 days)”
Quote in the paperSubstantial claim - Findingown data
Targeted treatments were started in 12 patients (11%).
“Targeted treatments were initiated in 12 patients (11%)”
- Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
“The molecular diagnosis was considered to have contributed to targeted treatment in 12 patients (11%).”
Quote in the paperSubstantial claim - Also stated in: § Changes in Clinical Management After the Ultra-Rapid Exome Sequencing Report and Perceived Utility · plain
- Findingcitation
Two diagnoses of Pearson syndrome caused by mitochondrial deletions were obtained through concurrent mitochondrial genome sequencing.
“Two molecular diagnoses of Pearson syndrome due to mitochondrial deletions were achieved through concurrent mitochondrial genome sequencing.17”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [17] Akesson, 2019, Early diagnosis of Pearson syndrome in neonatal intensive care following rapid mitochondrial genome sequencing in tandem with exome sequencing., Eur J Hum Genet source
Not checked in the free run.
- Findingown data
The mean time from sample receipt to the ultra-rapid exome sequencing report was 3.3 days, with a 95% CI of 3.2 to 3.5 days.
“The mean time from sample receipt to ultra-rapid exome sequencing report was 3.3 days (95% CI, 3.2-3.5 days)”
Quote in the paperSubstantial claim - Findingown data
One hundred and two reports (94%) were issued within the 5-calendar-day performance target.
“One hundred and two reports (94%) were issued within the performance target of 5 calendar days.”
Quote in the paperSubstantial claim - Findingown data
The longest component was the time from hospital admission to clinical genetics referral, with a mean of 8.1 days (95% CI, 6.0-10.8 days).
“The longest component was time from hospital admission to clinical genetics referral, which had a mean time of 8.1 days (95% CI, 6.0-10.8days).”
Quote in the paperSubstantial claim - Findingcitation
Four diagnoses were initially reported as variants of uncertain significance but were upgraded with additional data, including publication of another novel gene, IREB2, 6 months later.
“Four diagno-ses were initially reported as variants of uncertain significance but upgraded with additional data, including publication of another novel gene, IREB2, 6 months later.20,21”
Quote in the paperNot a substantial claim0 of 2 sources checked - Findingown data
Among 35 of the 62 NICU patients, the molecular diagnostic yield was 56.0% (95% CI, 41.9%-66.1%).
“Among 35 of the 62 patients enrolled from the NICU, the molecular diagnostic yield was 56.0% (95% CI, 41.9%-66.1%).”
Quote in the paperSubstantial claim - Findingcitation
The study found a 3-fold reduction in the mean time from hospital admission to molecular diagnosis compared with the prior Australian rapid exome sequencing study conducted in 2016-2017 at 2 centers.
“with a 3-fold reduction in the mean time from hospital admission to molecular diagnosis compared with the prior Australian rapid exome sequencing study 8 conducted in 2016-2017 at 2 centers.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Stark, 2018, Meeting the challenges of implementing rapid genomic testing in acute pediatric care., Genet Med source
Not checked in the free run.
- Findingreasoning
Recruitment rates varied markedly between sites.
“However, there was marked variation in the rates of recruitment between sites”
Quote in the paperNot a substantial claim - Findingown data
The duration of each diagnostic step varied little, suggesting a high level of consistency.
“there was little variability in the duration of each step of the diagnostic pathway, indicative of a high degree of consistency.”
Quote in the paperNot a substantial claim - Findingown data
After the ultra-rapid exome sequencing report, clinicians identified changes in clinical management for 48 of 108 patients (44%).
“After the ultra-rapid exome sequencing report, changes in clinical management were identified by clinicians for 48 of 108 patients (44%).”
Quote in the paperSubstantial claim - Findingown data
Changes in clinical management were considered to have occurred in 35 of 62 NICU patients (56%).
“Changes in clinical management were considered as having occurred in 35 of 62 patients (56%) from the NICU”
Quote in the paperSubstantial claim - Findingown data
Among 51 of the 93 patients approved by all expert panel members, the molecular diagnostic yield was 57.0% (95% CI, 43.0%-63.4%).
“Among 51 of the 93 patients approved by all the expert panel members, the molecular diagnostic yield was 57.0% (95% CI, 43.0%-63.4%).”
Quote in the paperSubstantial claim - Findingown data
Among 4 of the 15 patients with expert panel disagreement, the molecular diagnostic yield was 27.0% (95% CI, 6.7%-46.7%).
“Among 4 of the 15 patients about whom there was disagreement among the expert panel members, the molecular diagnostic yield was 27.0% (95% CI, 6.7%-46.7%).”
Quote in the paperNot a substantial claim - Findingown data
The program markedly shortened the average time to molecular diagnosis.
“the substantial reduction in the mean time to molecular diagnosis achieved by the program”
Quote in the paperSubstantial claim - Findingown data
Changes in clinical management were considered to have occurred in 17 of 36 PICU patients (47%).
“and in 17 of 36 patients (47%) from the PICU.”
Quote in the paperSubstantial claim - Findingown data
The longest step in the diagnostic process was the interval between hospital admission and starting the test.
“The longest component of the diagnostic pathway remained time from hospital admission to test initiation”
Quote in the paperSubstantial claim - Interpretationown data
The study indicates that ultra-rapid genomic testing is feasible for critically ill pediatric patients with suspected monogenic conditions within the Australian public health care system.
“This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system.”
- Also stated in: § Discussion · boosted
“This prospective study of 108 critically ill infants and children from multiple sites across Australia demonstrates the feasibility of a national, highly coordinated clinical and laboratory ultra-rapid genomic diagnosis program in a public health care system”
Quote in the paperSubstantial claim - Also stated in: § Discussion · boosted
- Interpretationreasoning
Custom procedures for identifying, shipping, and tracking samples were crucial for preventing delays.
“specifically designed procedures for sample identification, shipping, and tracking were invaluable in preventing delays.”
Quote in the paperSubstantial claim - Interpretationreasoning
Results such as molecular diagnostic yield might not apply to different health care systems or service delivery models.
“outcomes such as molecular diagnostic yield may not be generalizable to other health care systems or service delivery models.”
Quote in the paperNot a substantial claim - Study design and conductcitation
All participating services reported strong readiness for implementation before the study started.
“expressed high levels of implementation readiness prior to study commencement.”
Quote in the paperNot a substantial claim - Interpretationown data
The ultra-rapid exome sequencing report was perceived as contributing to clinical management regardless of whether a molecular diagnosis was made.
“The ultra-rapid exome sequencing report was perceived as contributing to the clinical management of the patients regardless of whether a molecular diagnosis was made.”
Quote in the paperSubstantial claim - Interpretationown data
Running an ultra-rapid diagnostic program across several clinical and laboratory sites involved major logistical difficulties.
“The logistical challenges in coordinating an ultra-rapid diagnosis program involving multiple clinical and laboratory sites were considerable”
Quote in the paperNot a substantial claim - Study design and conductcitation
All participating hospitals had clinical genetics services on site.
“all participating hospitals had clinical genetics services on site”
Quote in the paperSubstantial claim - Interpretationown data
Ultra-rapid genomic testing appears feasible for critically ill children with suspected monogenic conditions within the Australian public health system.
“This study suggests feasibility of ultra-rapid genomic testing in critically ill pediatric patients with suspected monogenic conditions in the Australian public health care system.”
Quote in the paperSubstantial claim - Premisecitation
A blinded randomized trial comparing rapid genome sequencing with standard care ended early due to loss of equipoise.
“a blinded randomized clinical trial 9 of rapid genome sequencing vs standard care was terminated prematurely due to loss of equipoise.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [9] Petrikin, 2018, The NSIGHT1-randomized controlled trial: rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants., NPJ Genom Med source
Not checked in the free run.
- Study design and conductreasoning
The descriptive approach used here and elsewhere may bias outcome reporting, especially when linking ultra-rapid exome results causally to later changes in clinical management.
“acknowledging this has the potential for biased reporting of outcomes, in particular in drawing a causal link between ultra-rapid exome sequencing results and subsequent changes in clinical management.”
Quote in the paperNot a substantial claim - Study design and conductreasoning
The study lacked the design and statistical power to detect differences in major clinical outcomes such as morbidity and mortality compared with standard care.
“this study was not designed or powered to measure differences in major clinical outcomes like morbidity and mortality against those that result from standard care of critically ill pediatric patients.”
Quote in the paperSubstantial claim
- Classified as probably not a substantial claim. 14
- May combine two claims. 18
Probably not a substantial claim: may not pass S3 (load-bearing).
Findingown dataThirty-four percent of participants were female.
“34% were female”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe median age of participants was 28 days, with a range from 0 days to 17 years.
“The median age of participants was 28 days (range, 0 days-17 years)”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe median time from sample receipt to the ultra-rapid exome sequencing report was 3 days, with a range of 2 to 7 days.
“the median time was 3 days (range, 2-7 days)”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataLaboratory 1 performed 94 tests, and laboratory 2 performed 14 tests.
“Laboratory 1 performed 94 tests and laboratory 2 performed 14 tests.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataRoutine trio ultra-rapid exome sequencing produced 45 molecular diagnoses, and extended approaches added 11 more.
“Routine ultra-rapid exome sequencing trio analyses resulted in 45 molecular diagnoses, with an additional 11 molecular diagnoses made through”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataThe mean sample transportation time was 1.6 days (95% CI, 1.4-1.9 days), even though the furthest hospital was 1600 km from the laboratory.
“The mean sample transportation time was 1.6 days (95% CI, 1.4-1.9days) despite the furthest hospital being 1600 km away from the laboratory site.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataTwo additional diagnoses were made by submitting novel gene candidates to GeneMatcher and matching them to multiple other cases in real time, which established novel gene-disease associations and enabled diagnostic reporting.
“Two further molecular diagnoses were made by submitting novel gene candidates to GeneMatcher 18 (an international data sharing platform) and matching to multiple other cases in real time, enabling establishment of novel genedisease associations and diagnostic reporting.19”
Quote in the paperSubstantial claim0 of 2 sources checked- cites [18] Sobreira, 2015, GeneMatcher: a matching tool for connecting investigators with an interest in the same gene., Hum Mutat source
Not checked in the free run.
- cites [19] Rehman, 2019, Biallelic loss of function variants in PPP1R21 cause a neurodevelopmental syndrome with impaired endocytic function., Hum Mutat source
Not checked in the free run.
May combine two claims.
Findingown dataOf the 11 extended diagnoses, 7 came from the original analysis, including 3 found by hypothesis-driven identification of single-gene copy number variants from exome data.
“Of these 11 molecular diagnoses, 7 were made as part of the original analysis, including 3 through hypothesis-driven identification of copy number variants affecting single genes from the exome sequencing data”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataA molecular diagnosis was made in 55 patients (51%), with 56 molecular diagnoses in total.
“A molecular diagnosis was established in 55 patients (51%).”
- Also stated in: § Molecular Diagnostic Yield · plain
“A total of 56 molecular diagnoses were made for 55 patients (51%)”
Quote in the paperSubstantial claim- Also stated in: § Molecular Diagnostic Yield · plain
May combine two claims.
FindingcitationRapid RNA studies confirmed the pathogenicity of a homozygous splice-site ASNS variant within 10 days, and 2 other variants of uncertain significance were reclassified as likely pathogenic after further phenotyping over 6 months.
“Rapid RNA studies confirmed the pathogenicity of a homozygous splicesite ASNS variant in 10 days, and 2 other variants of uncertain significance were reclassified as likely pathogenic after further phenotyping during a period of 6 months.22”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [22] Richmond, 2020, Rapid identification of biallelic SPTB mutation in a neonate with severe congenital hemolytic anemia and liver failiure., Mol Syndromol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown dataThe ward distribution was 57% NICU, 33% PICU, and 9% other hospital wards.
“62 patients (57%) were admitted to NICUs, 36 patients (33%) were admitted to PICUs, and 10 patients (9%) were from other hospital wards.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown dataThe two-laboratory model delivered reliable service according to clinical need, and 94% of tests were reported within the 5-day target.
“The 2 laboratories together were able to provide consistent service based on clinical demand, with 94% of tests reported before the target time of 5 calendar days.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown dataA greater proportion of reports were returned before hospital discharge or death, and the reports contributed to palliative care decisions in a greater proportion of patients who died.
“A greater proportion of reports were returned prior to hospital discharge or death and the reports formed part of the palliative care decisions in a greater proportion of the patients who died.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [8] Stark, 2018, Meeting the challenges of implementing rapid genomic testing in acute pediatric care., Genet Med source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductnone givenNo participants were lost to follow-up, and all data collection was finished.
“No patients were lost to follow-up and all data collection was complete.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing). May combine two claims.
PremisecitationScaling up innovations in health care systems is complex and requires both structure and local adaptability, aided by participatory culture, distributed leadership, transparent outcome assessment, collective learning, and adaptation.
“the successful spread and scaling up of innovations in health care systems is complex, and necessitates both structure and adaptability to the local context, benefitting from a participatory culture, distributed leadership, transparent assessment of outcomes, collective learning, and adaptation.10”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10] Greenhalgh, 2019, Spreading and scaling up innovation and improvement., BMJ source
Not checked in the free run.
Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).
PremisecitationPurposeful implementation strategies that account for change being iterative, nonlinear, and multicomponent can help streamline scaling up rapid diagnostic programs across health care systems and avoid costly trial and error at multiple sites.
“Developing purposeful implementation strategies that recognize the iterative, nonlinear, and multicomponent nature of change has the potential to streamline the process of scaling up rapid diagnostic programs across health care systems, preventing costly trial and error at multiple sites.11”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [11] Braithwaite, 2018, When complexity science meets implementation science: a theoretical and empirical analysis of systems change., BMC Med source
Not checked in the free run.
Classified as probably not a substantial claim.
Study design and conductcitationVariants relevant to the patient's phenotype were classified according to ACMG standards.
“Variants relevant to patient phenotype were classified based on the standards of the American College of Medical Genetics and Genomics. 16”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [16] Richards, 2015, Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology., Genet Med source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRapid genomic testing studies have mostly focused on NICU infants, but some have also included other critically ill children, such as those in PICUs.
“Although studies of rapid genomic testing have primarily included infants in neonatal intensive care units (NICUs), 1,[3][4][5]9 a minority of studies have included other critically ill children such as those in pediatric intensive care units (PICUs).2,[6][7][8]”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites 1,[3][4][5]9
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- cites 2,[6][7][8]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningUneven population distribution and the transfer of complex cases to specialist pediatric hospitals may partly account for the differences in recruitment rates.
“which may be partly explained by the uneven distribution of the Australian population and the transfer of complex patients to specialist pediatric hospitals.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductnone givenAll clinical and laboratory services participated voluntarily.
“all clinical and laboratory services participated on a voluntary basis”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
InterpretationreasoningDifferences in clinician engagement, prior experience, and perceived usefulness across sites may also partly explain the variation in recruitment.
“It may also partly represent different levels of clinician engagement, prior experience, and perceptions of utility at different sites.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
PremisecitationRapid genomic testing places demands on all stages of the clinical and laboratory process, calling for timely patient identification, skilled evaluation, appropriate counseling, and robust communication and coordination.
“rapid genomic testing challenges all the components of the clinical and laboratory pathway, necessitating timely patient identification, skilled assessment, appropriate counseling, and a high degree of communication and coordination in emotionally charged and rapidly evolving clinical situations.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [8] Stark, 2018, Meeting the challenges of implementing rapid genomic testing in acute pediatric care., Genet Med source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductcitationThe clinical genetics service led the service delivery model, following the preferences of each participating center.
“the service delivery model implemented was led by the clinical genetics service as per participating center preferences.”
Quote in the paperNot a substantial claimMay combine two claims.
PremisecitationInadequate funding, insufficient pediatric workforce preparation, and the high resource demands of rapid testing are substantial barriers to wide adoption.
“The lack of health care funding, the underpreparedness of the pediatric workforce, and the resource-intensive nature of rapid testing represent significant barriers to widespread adoption.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [8] Stark, 2018, Meeting the challenges of implementing rapid genomic testing in acute pediatric care., Genet Med source
Not checked in the free run.
- cites [14] Stark, 2019, Attitudes of Australian health professionals towards rapid genomic testing in neonatal and paediatric intensive care., Eur J Hum Genet source
Not checked in the free run.
- cites [23] Clark, 2019, Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation., Sci Transl Med source
Not checked in the free run.
May combine two claims.
PremisecitationNo agreement exists on how to assess rapid testing programs or what level of evidence should guide health care system funding.
“there is no consensus on how to evaluate rapid testing programs or what evidentiary threshold should be used for health care system funding.”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [25] Friedman, 2019, Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application?, Genet Med source
Not checked in the free run.
- cites [26] Grosse, 2019, Genomic sequencing in acutely ill infants: what will it take to demonstrate clinical value?, Genet Med source
Not checked in the free run.
The paper relies on this without support.
In critical care, genomic test results must be delivered quickly to be clinically useful.
“In the critical care setting, genomic testing results need to be delivered rapidly to be useful”
The paper relies on this without support.
Mean turnaround times for early rapid testing programs have been between 7 and 23 days.
“the mean turnaround times achieved by nascent rapid testing programs have ranged from 7 to 23 days.”
The paper relies on this without support.
Moving academic single-center rapid genomic testing into health care system implementation requires robust clinical and laboratory pathways for reliable and consistent delivery.
“Translating the experience of academic single-center studies into implementation across health care systems requires the development of robust clinical and laboratory pathways to deliver rapid genomic testing reliably and consistently.”
The paper relies on this without support.
Health care is a complex adaptive system.
“Health care is a complex adaptive system”
The paper relies on this without support.
Successful adoption of rapid genomic testing depends on multidisciplinary teams changing practices across multiple sites, not only on laboratory scalability.
“the successful adoption of innovations such as rapid genomic testing relies not only on the scalability of the laboratory testing, but on the multidisciplinary teams of intensive care physicians, medical subspecialists, clinical geneticists, genetic counselors, laboratory scientists, and bioinformaticians simultaneously changing practices across multiple sites to provide consistent service.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
From diagnosis, families experience considerable grief and need intense support as the disease evolves.
“From diagnosis, families experience considerable grief and need intense support as the disease evolves 160,161 .”
From Developmental and epileptic encephalopathies (2024) · cites this paper as [161]
The Discussion (page not available) says rapid genomic testing requires appropriate counseling in emotionally charged, rapidly evolving clinical situations, and Participant Demographics reports that genetic counselors saw 88% of families. These passages support a need for counseling around diagnosis, but they do not establish that families experience considerable grief from diagnosis or need intense support as the disease evolves. (LLM, conf=0.76)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Ward-specific management changes exceed the reported total
MajorThe NICU and PICU groups are distinct, so their reported management changes alone total 52 patients. That exceeds the stated total of 48, even before patients from other wards are considered.
“After the ultra-rapid exome sequencing report, changes in clinical management were identified by clinicians for 48 of 108 patients (44%).”
“Changes in clinical management were considered as having occurred in 35 of 62 patients (56%) from the NICU and in 17 of 36 patients (47%) from the PICU.”
Unanimously approved subgroup yield is overstated
MinorA diagnosis in 51 of 93 unanimously approved patients gives a yield of 54.8%, not 57.0%.
Reported 57 · recomputed 54.83871
“Among 51 of the 93 patients approved by all the expert panel members, the molecular diagnostic yield was 57.0% (95% CI, 43.0%-63.4%).”
Cites
Harris, P. A., Taylor, R., Thielke, R., Payne, J., Gonzalez, N., & Conde, J. G. (2009) · Journal of Biomedical Informatics · doi:10.1016/j.jbi.2008.08.010 · Cited by 51,384 · see citing works
Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W. W., Hegde, M., Lyon, E., Spector, E., et al. (2015) · Genetics in Medicine · doi:10.1038/gim.2015.30 · Cited by 32,594 · see citing works
Damschroder, L. J., Aron, D. C., Keith, R. E., Kirsh, S. R., Alexander, J. A., & Lowery, J. C. (2009) · Implementation Science · doi:10.1186/1748-5908-4-50 · Cited by 14,496 · see citing works
Curran, G. M., Bauer, M., Mittman, B., Pyne, J. M., & Stetler, C. (2012) · Medical Care · doi:10.1097/mlr.0b013e3182408812 · Cited by 4,058 · see citing works
GeneMatcher: a matching tool for connecting investigators with an interest in the same gene.
Sobreira, N., Schiettecatte, F., Valle, D., & Hamosh, A. (2015) · Human Mutation · doi:10.1002/humu.22844 · Cited by 1,529 · see citing works
Braithwaite, J., Churruca, K., Long, J. C., Ellis, L. A., & Herkes, J. (2018) · BMC Medicine · doi:10.1186/s12916-018-1057-z · Cited by 845 · see citing works
Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization
Farnaes, L., Hildreth, A., Sweeney, N. M., Clark, M. M., Chowdhury, S., Nahas, S., Cakici, J. A., Benson, W., Kaplan, R. H., Kronick, R., et al. (2018) · npj Genomic Medicine · doi:10.1038/s41525-018-0049-4 · Cited by 445 · see citing works
Use of Exome Sequencing for Infants in Intensive Care Units
Meng, L., Pammi, M., Saronwala, A., Magoulas, P. L., Ghazi, A. R., Vetrini, F., Zhang, J., He, W., Dharmadhikari, A. V., Qu, C., et al. (2017) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2017.3438 · Cited by 429 · see citing works
Spreading and scaling up innovation and improvement
Greenhalgh, T., & Papoutsi, C. (2019) · BMJ · doi:10.1136/bmj.l2068 · Cited by 382 · see citing works
Kingsmore, S. F., Cakici, J. A., Clark, M. M., Gaughran, M., Feddock, M., Batalov, S., Bainbridge, M. N., Carroll, J. M., Caylor, S. A., Clarke, C., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.08.009 · Cited by 354 · see citing works
Self-citationClark, M. M., Hildreth, A., Batalov, S., Ding, Y., Chowdhury, S., Watkins, K., Ellsworth, K., Camp, B., Kint, C. I., Yacoubian, C., et al. (2019) · Science Translational Medicine · doi:10.1126/scitranslmed.aat6177 · Cited by 300 · see citing works
Self-citationWhole genome sequencing reveals that genetic conditions are frequent in intensively ill children
Disease, N. B., French, C. E., Next Generation Children Project, Delon, I., Dolling, H., Sanchis‐Juan, A., Shamardina, O., Mégy, K., Abbs, S. J., Austin, T., et al. (2019) · Intensive Care Medicine · doi:10.1007/s00134-019-05552-x · Cited by 253 · see citing works
Petrikin, J. E., Cakici, J. A., Clark, M. M., Willig, L. K., Sweeney, N. M., Farrow, E. G., Saunders, C. J., Thiffault, I., Miller, N. A., Zellmer, L., et al. (2018) · npj Genomic Medicine · doi:10.1038/s41525-018-0045-8 · Cited by 229 · see citing works
Meeting the challenges of implementing rapid genomic testing in acute pediatric care.
Stark, Z., Lunke, S., Brett, G. R., Tan, N. B., Stapleton, R., Kumble, S., Yeung, A., Phelan, D. G., Chong, B., Fanjul-Fernandez, M., et al. (2018) · Genetics in Medicine · doi:10.1038/gim.2018.37 · Cited by 159 · see citing works
Self-citationRapid whole genome sequencing has clinical utility in children in the PICU
Sanford, E. F., Clark, M. M., Farnaes, L., Williams, M. R., Perry, J. C., Ingulli, E. G., Sweeney, N. M., Doshi, A., Gold, J. J., Briggs, B., et al. (2019) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000002056 · Cited by 150 · see citing works
Mestek, L., Clement, E. M., Jones, W. D., Drury, S., Ocaka, L., Gagunashvili, A. N., Stabej, P. L. Q., Bacchelli, C., Jani, N., Rahman, S., et al. (2018) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2018-105396 · Cited by 128 · see citing works
Australian Genomics: A Federated Model for Integrating Genomics into Healthcare
Stark, Z., Boughtwood, T. F., Phillips, P. M., Christodoulou, J., Hansen, D. P., Braithwaite, J., Newson, A. J., Gaff, C., Sinclair, A. H., & North, K. N. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.06.003 · Cited by 125 · see citing works
Self-citationGubbels, C. S., VanNoy, G. E., Madden, J. A., Copenheaver, D., Yang, S., Wojcik, M. H., Gold, N. B., Genetti, C. A., Stoler, J. M., Parad, R. B., et al. (2019) · Genetics in Medicine · doi:10.1038/s41436-019-0708-6 · Cited by 120 · see citing works
Absence of iron-responsive element-binding protein 2 causes a novel neurodegenerative syndrome.
Costain, G., Ghosh, M. C., Maio, N., Carnevale, A., Si, Y. C., Rouault, T. A., & Yoon, G. (2019) · Brain · doi:10.1093/brain/awz072 · Cited by 55 · see citing works
Genome-wide sequencing in acutely ill infants: genomic medicine’s critical application?
Friedman, J. M., Bombard, Y., Cornel, M. C., Fernandez, C. V., Junker, A. K., Plon, S. E., Stark, Z., & Knoppers, B. M. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0055-z · Cited by 44 · see citing works
Self-citationStark, Z., Nisselle, A., McClaren, B., Lynch, F., Best, S., Long, J. C., Martyn, M., Patel, C., Schlapbach, L. J., Barnett, C., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0429-y · Cited by 43 · see citing works
Self-citationIREB2-associated neurodegeneration.
Cooper, M. S., Stark, Z., Lunke, S., Zhao, T., & Amor, D. J. (2019) · Brain · doi:10.1093/brain/awz183 · Cited by 28 · see citing works
Self-citationAkesson, L. S., Eggers, S., Love, C. J., Chong, B., Krzesinski, E. I., Brown, N. J., Tan, T. Y., Richmond, C. M., Thorburn, D. R., Christodoulou, J., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0477-3 · Cited by 28 · see citing works
Self-citationRehman, A. U., Najafi, M., Kambouris, M., Al‐Gazali, L., Makrythanasis, P., Rad, A., Maroofian, R., Rajab, A., Stark, Z., Hunter, J. V., et al. (2018) · Human Mutation · doi:10.1002/humu.23694 · Cited by 22 · see citing works
Self-citationGenomic sequencing in acutely ill infants: what will it take to demonstrate clinical value?
Grosse, S. D., & Farnaes, L. (2019) · Genetics in Medicine · doi:10.1038/s41436-018-0124-3 · Cited by 19 · see citing works
Richmond, C. M., Campbell, S., Foo, H. W., Lunke, S., Stark, Z., Moody, A., Bannister, E., Greenway, A., & Brown, N. (2020) · Molecular Syndromology · doi:10.1159/000505886 · Cited by 12 · see citing works
Self-citationRehman (2019) · Human Mutation · doi:10.1002/humu.2019.40.issue-3 · Cited by 1 · see citing works
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Dimmock, D., Caylor, S. A., Waldman, B. M., Benson, W., Ashburner, C., Carmichael, J., Carroll, J. M., Cham, E. M., Chowdhury, S., Cleary, J. P., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.05.008 · Cited by 259 · see citing works
Genomic newborn screening for rare diseases
Stark, Z., & Scott, R. H. (2023) · Nature Reviews Genetics · doi:10.1038/s41576-023-00621-w · Cited by 230 · see citing works
Self-citationThe NICUSeq Study Group, Krantz, I. D., Medne, L., Weatherly, J., Wild, K. T., Biswas, S., Devkota, B., Hartman, T. R., Brunelli, L., Fishler, K. P., et al. (2021) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2021.3496 · Cited by 175 · see citing works
Integrated multi-omics for rapid rare disease diagnosis on a national scale
Lunke, S., Bouffler, S. E., Patel, C., Sandaradura, S. A., Wilson, M., Pinner, J. R., Hunter, M. F., Barnett, C., Wallis, M., Kamien, B., et al. (2023) · Nature Medicine · doi:10.1038/s41591-023-02401-9 · Cited by 155 · see citing works
Self-citationKnowles, J. K., Helbig, I., Metcalf, C. S., Lubbers, L. S., Isom, L. L., Demarest, S., Goldberg, E. M., George, A. L., Lerche, H., Weckhuysen, S., et al. (2022) · Epilepsia · doi:10.1111/epi.17332 · Cited by 149 · see citing works
Beyond the exome: What’s next in diagnostic testing for Mendelian conditions
Wojcik, M. H., Reuter, C. M., Marwaha, S., Mahmoud, M., Duyzend, M., Barseghyan, H., Yuan, B., Boone, P. M., Groopman, E., Délot, E. C., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.06.009 · Cited by 134 · see citing works
Self-citationDevelopmental and epileptic encephalopathies
Scheffer, I. E., Zuberi, S., Mefford, H. C., Guerrini, R., & McTague, A. (2024) · Nature Reviews Disease Primers · doi:10.1038/s41572-024-00546-6 · Cited by 128 · see citing works
Accelerated identification of disease-causing variants with ultra-rapid nanopore genome sequencing
Goenka, S. D., Gorzynski, J. E., Shafin, K., Fisk, D. G., Pesout, T., Jensen, T. D., Monlong, J., Chang, P.-C., Baid, G., Bernstein, J. A., et al. (2022) · Nature Biotechnology · doi:10.1038/s41587-022-01221-5 · Cited by 107 · see citing works
Towards improved genetic diagnosis of human differences of sex development
Délot, E. C., & Vilain, E. J. N. (2021) · Nature Reviews Genetics · doi:10.1038/s41576-021-00365-5 · Cited by 100 · see citing works
Bournazos, A., Riley, L. G., Bommireddipalli, S., Adès, L. C., Akesson, L. S., Al-Shinnag, M., Alexander, S. I., Archibald, A. D., Balasubramaniam, S., Berman, Y. D., et al. (2021) · Genetics in Medicine · doi:10.1016/j.gim.2021.09.001 · Cited by 95 · see citing works
Self-citationThe Role of Genome Sequencing in Neonatal Intensive Care Units
Kingsmore, S. F., & Cole, F. S. (2022) · Annual Review of Genomics and Human Genetics · doi:10.1146/annurev-genom-120921-103442 · Cited by 95 · see citing works
Chung, C. C. Y., Hue, S. P. Y., Ng, N. Y. T., Doong, P. H. L., Chu, A. T.-W., & Chung, B. H. (2023) · Genetics in Medicine · doi:10.1016/j.gim.2023.100896 · Cited by 93 · see citing works
Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review
Kingsmore, S. F., Nofsinger, R. R., & Ellsworth, K. (2024) · npj Genomic Medicine · doi:10.1038/s41525-024-00404-0 · Cited by 89 · see citing works
Stark, Z., Boughtwood, T. F., Haas, M., Braithwaite, J., Gaff, C., Goranitis, I., Spurdle, A. B., Hansen, D. P., Hofmann, O., Laing, N. G., et al. (2023) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2023.01.018 · Cited by 79 · see citing works
Self-citationClinical implications of host genetic variation and susceptibility to severe or critical COVID-19
van der Made, C. I., Netea, M. G., van de Veerdonk, F. L., & Hoischen, A. (2022) · Genome Medicine · doi:10.1186/s13073-022-01100-3 · Cited by 78 · see citing works
Sweeney, N. M., Nahas, S., Chowdhury, S., Batalov, S., Clark, M. M., Caylor, S. A., Cakici, J. A., Nigro, J. J., Ding, Y., Veeraraghavan, N., et al. (2021) · npj Genomic Medicine · doi:10.1038/s41525-021-00192-x · Cited by 74 · see citing works
Rapid genomic testing for critically ill children: time to become standard of care?
Stark, Z., & Ellard, S. (2021) · European Journal of Human Genetics · doi:10.1038/s41431-021-00990-y · Cited by 72 · see citing works
Self-citationArtificial Intelligence in Cardiac Surgery: Transforming Outcomes and Shaping the Future
Leivaditis, V., Beltsios, E. T., Papatriantafyllou, A., Grapatsas, K., Mulita, F., Kontodimopoulos, N., Baikoussis, N. G., Tchabashvili, L., Tasios, K., Maroulis, I., et al. (2025) · Clinics and Practice · doi:10.3390/clinpract15010017 · Cited by 70 · see citing works
Genomic autopsy to identify underlying causes of pregnancy loss and perinatal death
Byrne, A. B., Arts, P., Ha, T., Kassahn, K. S., Pais, L. S., O’Donnell‐Luria, A., Aguet, F., Arachchi, H., Austin-Tse, C. A., Babb, L., et al. (2023) · Nature Medicine · doi:10.1038/s41591-022-02142-1 · Cited by 68 · see citing works
Self-citationRoberts, M. C., Fohner, A. E., Landry, L. G., Olstad, D. L., Smit, A. K., Turbitt, E., & Allen, C. G. (2021) · Genome Medicine · doi:10.1186/s13073-021-00911-0 · Cited by 64 · see citing works
Franck, L. S., Kriz, R. M., Rego, S., Garman, K., Hobbs, C., & Dimmock, D. (2021) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2021.05.045 · Cited by 59 · see citing works
The genetics of mitochondrial disease: dissecting mitochondrial pathology using multi‐omic pipelines
Alston, C. L., Stenton, S. L., Hudson, G., Prokisch, H., & Taylor, R. W. (2021) · The Journal of Pathology · doi:10.1002/path.5641 · Cited by 58 · see citing works
Lumaka, A. Z., Carstens, N., Devriendt, K., Krause, A., Kulohoma, B. W., Kumuthini, J., Mubungu, G. L., Mukisa, J., Nel, M., Olanrewaju, T. O., et al. (2022) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-022-02391-w · Cited by 54 · see citing works
Stolz, J. R., Foote, K. M., Veenstra‐Knol, H. E., Pfundt, R., ten Broeke, S. W., de Leeuw, N., Roht, L., Pajusalu, S., Part, R., Rebane, I., et al. (2021) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2021.07.007 · Cited by 53 · see citing works
Self-citationPandey, R., Brennan, N. F., Trachana, K., Katsandres, S. C., Bodamer, O. A., Belmont, J. W., Veenstra, D. L., & Peng, S. (2025) · Genetics in Medicine · doi:10.1016/j.gim.2025.101398 · Cited by 52 · see citing works
Cost-Effectiveness of Targeted Exome Analysis as a Diagnostic Test in Glomerular Diseases
Jayasinghe, K., Wu, Y., Stark, Z., Kerr, P. G., Mallett, A. J., Gaff, C., Martyn, M. M., Goranitis, I., & Quinlan, C. (2021) · Kidney International Reports · doi:10.1016/j.ekir.2021.08.028 · Cited by 49 · see citing works
Self-citationGenome sequencing as a generic diagnostic strategy for rare disease
Schobers, G., Derks, R. C., den Ouden, A., Swinkels, H. L., van Reeuwijk, J., Bosgoed, E., Lugtenberg, D., Sun, S. M., Corominas, J., Weiss, M. M., et al. (2024) · Genome Medicine · doi:10.1186/s13073-024-01301-y · Cited by 49 · see citing works
Goranitis, I., Wu, Y., Lunke, S., White, S. M., Tan, T. Y., Yeung, A., Hunter, M. F., Martyn, M. M., Gaff, C., & Stark, Z. (2022) · Genetics in Medicine · doi:10.1016/j.gim.2022.01.013 · Cited by 49 · see citing works
Self-citationParental experiences of ultrarapid genomic testing for their critically unwell infants and children
Brett, G. R., Martyn, M., Lynch, F., de Silva, M. G., Ayres, S., Gallacher, L., Boggs, K., Baxendale, A., Schenscher, S., King-Smith, S., et al. (2020) · Genetics in Medicine · doi:10.1038/s41436-020-0912-4 · Cited by 47 · see citing works
Self-citationLearning from scaling up ultra-rapid genomic testing for critically ill children to a national level
Best, S., Brown, H. L., Lunke, S., Patel, C., Pinner, J. R., Barnett, C., Wilson, M., Sandaradura, S. A., McClaren, B., Brett, G. R., et al. (2021) · npj Genomic Medicine · doi:10.1038/s41525-020-00168-3 · Cited by 47 · see citing works
Self-citationMulticenter Consensus Approach to Evaluation of Neonatal Hypotonia in the Genomic Era: A Review
Morton, S. U., Christodoulou, J., Costain, G., Francesco Muntoni, A., Wakeling, E. L., Wojcik, M. H., French, C. E., Szuto, A., Dowling, J. J., Cohn, R. D., et al. (2022) · JAMA Neurology · doi:10.1001/jamaneurol.2022.0067 · Cited by 45 · see citing works
Self-citationReclassification of the Etiology of Infant Mortality With Whole-Genome Sequencing
Owen, M. J., Wright, M. S., Batalov, S., Kwon, Y., Ding, Y., Chau, K. K., Chowdhury, S., Sweeney, N. M., Kiernan, E. A., Richardson, A. C., et al. (2023) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.54069 · Cited by 45 · see citing works
Integrating rapid exome sequencing into NICU clinical care after a pilot research study
D’Gama, A. M., del Rosario, M. C., Bresnahan, M., Yu, T. W., Wojcik, M. H., & Agrawal, P. B. (2022) · npj Genomic Medicine · doi:10.1038/s41525-022-00326-9 · Cited by 39 · see citing works
Regrow or Repair: An Update on Potential Regenerative Therapies for the Kidney
Little, M., & Humphreys, B. (2021) · Journal of the American Society of Nephrology · doi:10.1681/asn.2021081073 · Cited by 23 · see citing works
Measures of Utility Among Studies of Genomic Medicine for Critically Ill Infants
Callahan, K. P., Mueller, R., Flibotte, J. J., Largent, E. A., & Feudtner, C. (2022) · JAMA Network Open · doi:10.1001/jamanetworkopen.2022.25980 · Cited by 37 · see citing works
Scholz, T., Blohm, M. E. G., Kortüm, F., Bierhals, T., Lessel, D., van der Ven, A. T., Lisfeld, J., Herget, T., Kloth, K., Singer, D., et al. (2021) · Neonatology · doi:10.1159/000516890 · Cited by 35 · see citing works
Rapid genome sequencing for pediatrics
Jezkova, J., Shaw, S., Taverner, N. V., & Williams, H. J. (2022) · Human Mutation · doi:10.1002/humu.24466 · Cited by 32 · see citing works
Giorgio, A. D., Bartolini, E., Calvo, P. L., Cananzi, M., Cirillo, F., Corte, C. D., Dionisi‐Vici, C., Indolfi, G., Iorio, R. F., Maggiore, G., et al. (2021) · Digestive and Liver Disease · doi:10.1016/j.dld.2021.03.004 · Cited by 31 · see citing works
Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016–2023*
Rodriguez, K. M., Vaught, J., Salz, L., Foley, J., Boulil, Z., VanDongen-Trimmer, H., Whalen, D., Oluchukwu, O., Liu, K. C., Burton, J., et al. (2024) · Pediatric Critical Care Medicine · doi:10.1097/pcc.0000000000003522 · Cited by 30 · see citing works
Diagnosis and Care of the Newborn with Epidermolysis Bullosa
Lucky, A. W., Whalen, J., Rowe, S., Marathe, K. S., & Gorell, E. S. (2021) · NeoReviews · doi:10.1542/neo.22-7-e438 · Cited by 30 · see citing works
Suzuki, H., Nozaki, M., Yoshihashi, H., Imagawa, K., Kajikawa, D., Yamada, M., Yamaguchi, Y., Morisada, N., Eguchi, M., Ohashi, S., et al. (2022) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2022.01.033 · Cited by 30 · see citing works
Keizer, R. A. C. M. O., Marouane, A., Kerstjens‐Frederikse, W. S., Deden, A. C., Lichtenbelt, K. D., Jonckers, T., Vervoorn, M., Vreeburg, M., Henneman, L., de Vries, L. S., et al. (2023) · European Journal of Pediatrics · doi:10.1007/s00431-023-04909-1 · Cited by 30 · see citing works
Akesson, L. S., Eggers, S., Love, C. J., Chong, B., Krzesinski, E. I., Brown, N. J., Tan, T. Y., Richmond, C. M., Thorburn, D. R., Christodoulou, J., et al. (2019) · European Journal of Human Genetics · doi:10.1038/s41431-019-0477-3 · Cited by 28 · see citing works
Self-citationHock, D. H., Caruana, N. J., Semcesen, L. N., Lake, N. J., Formosa, L. E., Amarasekera, S. S. C., Stait, T. L., Tregoning, S., Frajman, L. E., Bournazos, A., et al. (2025) · Genome Medicine · doi:10.1186/s13073-025-01467-z · Cited by 28 · see citing works
Self-citationGoranitis, I., Best, S., Christodoulou, J., Boughtwood, T. F., & Stark, Z. (2021) · European Journal of Human Genetics · doi:10.1038/s41431-021-00874-1 · Cited by 28 · see citing works
Self-citationMergnac, J.-P., Wiedemann, A., Chéry, C., Ravel, J., Namour, F., Guéant, J., Feillet, F., & Oussalah, A. (2021) · Human Genetics · doi:10.1007/s00439-021-02358-0 · Cited by 28 · see citing works
Parents’ experiences of decision making for rapid genomic sequencing in intensive care
Lynch, F., Nisselle, A. E., Stark, Z., Gaff, C., & McClaren, B. (2021) · European Journal of Human Genetics · doi:10.1038/s41431-021-00950-6 · Cited by 26 · see citing works
Self-citationDenommé‐Pichon, A., Vitobello, A., Olaso, R., Ziegler, A. C., Jeanne, M., Mau‐Them, F. T., Couturier, V., Racine, C., Isidor, B., Pöe, C., et al. (2021) · European Journal of Human Genetics · doi:10.1038/s41431-021-00998-4 · Cited by 26 · see citing works
Bowman‐Smart, H., Vears, D. F., Brett, G. R., Martyn, M. M., Stark, Z., & Gyngell, C. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01140-8 · Cited by 26 · see citing works
Self-citationAre We Ready for Whole Population Genomic Sequencing of Asymptomatic Newborns?
Vears, D. F., Savulescu, J., Christodoulou, J., Wall, M., & Newson, A. J. (2023) · Pharmacogenomics and Personalized Medicine · doi:10.2147/pgpm.s376083 · Cited by 26 · see citing works
Self-citationMcDermott, H., Sherlaw‐Sturrock, C., Baptista, J., Hartles-Spencer, L., & Naik, S. (2022) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2022.104571 · Cited by 25 · see citing works
Lumaka, A. Z., Fasquelle, C., Debray, F., Alkan, S., Jacquinet, A., Harvengt, J., Boemer, F., Mulder, A., Vaessen, S., Viellevoye, R., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24044003 · Cited by 25 · see citing works
Ouyang, X., Zhang, Y., Zhang, L., Luo, J., Zhang, T., Hu, H., Liu, L., Zhong, L., Zeng, S., Xu, P., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.725259 · Cited by 25 · see citing works
SeqFirst: Building equity access to a precise genetic diagnosis in critically ill newborns
Wenger, T. L., Scott, A. A., Kruidenier, L., Sikes, M. C., Keefe, A., Buckingham, K. J., Marvin, C. T., Shively, K. M., Bacus, T. J., Sommerland, O. M., et al. (2025) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2025.02.003 · Cited by 24 · see citing works
Lymphatic anomalies during lifetime in patients with Noonan syndrome: Retrospective cohort study
Swarts, J. W., Kleimeier, L. E. R., Leenders, E. K. S. M., Rinne, T., Klein, W. M., & Draaisma, J. M. T. (2022) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62955 · Cited by 24 · see citing works
Amarasekera, S. S. C., Hock, D. H., Lake, N. J., Calvo, S. E., Grønborg, S. W., Krzesinski, E. I., Amor, D. J., Fahey, M. C., Simons, C., Wibrand, F., et al. (2023) · Human Molecular Genetics · doi:10.1093/hmg/ddad069 · Cited by 23 · see citing works
Self-citationZhu, T., Gong, X., Bei, F., Ma, L., Chen, Y., Zhang, Y., Wang, X., Sun, J., Wang, J., Qiu, G., et al. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.565078 · Cited by 22 · see citing works
The role of chromosomal microarray and exome sequencing in prenatal diagnosis
Chau, M. H. K., & Choy, K. W. (2021) · Current Opinion in Obstetrics & Gynecology · doi:10.1097/gco.0000000000000692 · Cited by 22 · see citing works
Teamwork in clinical genomics: A dynamic sociotechnical healthcare setting
Best, S., Brown, H. L., Stark, Z., Long, J. C., Ng, L., Braithwaite, J., & Taylor, N. J. (2021) · Journal of Evaluation in Clinical Practice · doi:10.1111/jep.13573 · Cited by 22 · see citing works
Self-citationAutomated reanalysis of genomic data for rare disease diagnostics at scale
Welland, M. J., Ahlquist, K. D., Fazio, P. D., Austin-Tse, C. A., Pais, L. S., Wedd, L., Bryen, S., Rius, R., Franklin, M., Morrison, C., et al. (2026) · Nature Medicine · doi:10.1038/s41591-026-04477-5 · Cited by 21 · see citing works
Self-citationUltra‐rapid emergency genomic diagnosis of Donahue syndrome in a preterm infant within 17 hours
Bamborschke, D., Özdemir, Ö., Kreutzer, M., Motameny, S., Thiele, H., Kribs, A., Dötsch, J., Altmüller, J., Nürnberg, P., & Çırak, S. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.61917 · Cited by 21 · see citing works
French, C. E., Dolling, H., Mégy, K., Sanchis‐Juan, A., Kumar, A. A., Delon, I., Wakeling, M. N., Mallin, L., Agrawal, S., Austin, T., et al. (2022) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2022.100113 · Cited by 20 · see citing works
How I treat thrombotic microangiopathy in the era of rapid genomics
Doreille, A., Rafat, C., Rondeau, É., & Mesnard, L. (2022) · Blood · doi:10.1182/blood.2022015583 · Cited by 20 · see citing works
Pezzoli, L., Pezzani, L., Bonanomi, E., Marrone, C., Scatigno, A., Cereda, A., Bedeschi, M. F., Selicorni, A., Gasperini, S., Bini, P., et al. (2021) · Journal of Cardiovascular Development and Disease · doi:10.3390/jcdd9010002 · Cited by 20 · see citing works
Fehlberg, Z., Stark, Z., Klaic, M., & Best, S. (2024) · Implementation Science Communications · doi:10.1186/s43058-024-00675-9 · Cited by 19 · see citing works
Self-citationAlix, T., Chéry, C., Josse, T., Bronowicki, J., Feillet, F., Guéant‐Rodriguez, R., Namour, F., Guéant, J., & Oussalah, A. (2023) · Human Genomics · doi:10.1186/s40246-023-00455-x · Cited by 19 · see citing works
Rapid acute care genomics: Challenges and opportunities for genetic counselors
Lynch, F., Nisselle, A. E., Gaff, C., & McClaren, B. (2020) · Journal of Genetic Counseling · doi:10.1002/jgc4.1362 · Cited by 19 · see citing works
Exome and Whole Genome Sequencing in the Neonatal Intensive Care Unit
Muriello, M. J. (2022) · Clinics in Perinatology · doi:10.1016/j.clp.2021.11.018 · Cited by 18 · see citing works
Determining the value of genomics in healthcare
Goranitis, I., Hayeems, R. Z., Smith, H. S., Buchanan, J. P., Weymann, D., Regier, D. A., Mackley, M. P., Scott, R. H., Hill, S. L., Chung, B. H., et al. (2025) · Nature Medicine · doi:10.1038/s41591-025-04061-3 · Cited by 17 · see citing works
Self-citationHirata, K., Okamoto, N., Ichikawa, C., Inoue, S., Nozaki, M., Banno, K., Takenouchi, T., Suzuki, H., & Kosaki, K. (2020) · American Journal of Medical Genetics Part A · doi:10.1002/ajmg.a.62012 · Cited by 17 · see citing works
Next generation sequencing in neonatology: what does it mean for the next generation?
Janvier, A., Barrington, K. J., & Lantos, J. D. (2022) · Human Genetics · doi:10.1007/s00439-022-02438-9 · Cited by 17 · see citing works
Xiao, F., Yan, K., Tang, M., Ji, X., Hu, L., Yang, L., & Zhou, W. (2022) · Expert Review of Molecular Diagnostics · doi:10.1080/14737159.2022.2123704 · Cited by 17 · see citing works
Challenges in the clinical understanding of genetic testing in birth defects and pediatric diseases
Findley, T. O., Parchem, J. G., Ramdaney, A., & Morton, S. U. (2023) · Translational Pediatrics · doi:10.21037/tp-23-54 · Cited by 16 · see citing works
Rosina, E., Pezzani, L., Apuril, E., Pezzoli, L., Marchetti, D., Bellini, M., Lucca, C., Meossi, C., Massimello, M., Mariani, M., et al. (2023) · Molecular Genetics & Genomic Medicine · doi:10.1002/mgg3.2316 · Cited by 16 · see citing works
Molecular Diagnostic Yield of Exome Sequencing and Chromosomal Microarray in Short Stature
Li, Q., Chen, Z., Wang, J., Xu, K., Fan, X., Gong, C., Wu, Z., Zhang, J., & Wu, N. (2023) · Archives of Pediatrics and Adolescent Medicine · doi:10.1001/jamapediatrics.2023.3566 · Cited by 15 · see citing works
Fatal Human Neurologic Infection Caused by Pigeon Avian Paramyxovirus-1, Australia
Hurley, S. M., Eden, J., Bingham, J., Rodriguez, M. J., Neave, M. J., Johnson, A., Howard‐Jones, A. R., Kok, J., Anazodo, A. C., McMullan, B. J., et al. (2023) · Emerging infectious diseases · doi:10.3201/eid2912.230250 · Cited by 15 · see citing works
The role of exome sequencing in childhood interstitial or diffuse lung disease
Temple, S. E. L., Ho, G., Bennetts, B., Boggs, K., Vidic, N., Mowat, D. R., Christodoulou, J., Schultz, A., Gayagay, T., Roscioli, T., et al. (2022) · Orphanet Journal of Rare Diseases · doi:10.1186/s13023-022-02508-1 · Cited by 15 · see citing works
Self-citationCo-design, implementation, and evaluation of plain language genomic test reports
Brett, G. R., Ward, A., Bouffler, S. E., Palmer, E. E., Boggs, K., Lynch, F., Springer, A., Nisselle, A. E., & Stark, Z. (2022) · npj Genomic Medicine · doi:10.1038/s41525-022-00332-x · Cited by 14 · see citing works
Self-citationBergen, N. J. V., Gunanayagam, K., Bournazos, A., Walvekar, A. S., Warmoes, M. O., Semcesen, L. N., Lunke, S., Bommireddipalli, S., Sikora, T., Patraskaki, M., et al. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24043582 · Cited by 14 · see citing works
Self-citationGenomic medicine in neonatal care: progress and challenges
D’Gama, A. M., & Agrawal, P. B. (2023) · European Journal of Human Genetics · doi:10.1038/s41431-023-01464-z · Cited by 14 · see citing works
Howell, K. B., White, S. M., McTague, A., D’Gama, A. M., Costain, G., Poduri, A., Scheffer, I. E., Chau, V., Smith, L., Stephenson, S. E. M., et al. (2025) · npj Genomic Medicine · doi:10.1038/s41525-025-00474-8 · Cited by 14 · see citing works
Self-citationWells, C. F., Boursier, G., Yauy, K., Pallarès-Ruiz, N., Méchin, D., Ruault, V., Tharreau, M., Blanchet, P., Pinson, L., Coubes, C., et al. (2022) · European Journal of Human Genetics · doi:10.1038/s41431-022-01133-7 · Cited by 14 · see citing works
Vears, D. F., Lynch, F., Nisselle, A. E., Ayres, S., & Stark, Z. (2023) · European Journal of Human Genetics · doi:10.1038/s41431-023-01477-8 · Cited by 14 · see citing works
Self-citationHospital-wide access to genomic data advanced pediatric rare disease research and clinical outcomes
French, C. E., Andrews, N. C., Beggs, A. H., Boone, P. M., Brownstein, C. A., Chopra, M., Chou, J. S., Chung, W. K., D’Gama, A. M., Doan, R. N., et al. (2024) · npj Genomic Medicine · doi:10.1038/s41525-024-00441-9 · Cited by 13 · see citing works
Clinical Application of Whole Exome Sequencing for Monogenic Disorders in PICU of China
Liu, Y., Hao, C., Li, K., Hu, X., Gao, H., Zeng, J., Guo, R., Liu, J., Guo, J. F., Li, Z., et al. (2021) · Frontiers in Genetics · doi:10.3389/fgene.2021.677699 · Cited by 13 · see citing works
Papandreou, A., Doykov, I., Śpiewak, J., Komarov, N., Habermann, S., Kurian, M. A., Mills, P. B., Mills, K. A., Gissen, P., & Heywood, W. (2022) · Developmental Medicine & Child Neurology · doi:10.1111/dmcn.15334 · Cited by 13 · see citing works
Bioinformatics, Sequencing Accuracy, and the Credibility of Clinical Genomics
Feero, W. G. (2020) · JAMA · doi:10.1001/jama.2020.19939 · Cited by 13 · see citing works
Owens, C. E., Tan, O., Kuroiwa‐Trzmielina, J., Shrestha, R. N., O'Brien, T. A., Tyrrell, V. J., & SCHOFIELD, D. J. (2024) · npj Precision Oncology · doi:10.1038/s41698-024-00711-w · Cited by 12 · see citing works
Opportunities and challenges for paediatricians requesting funded genomic tests for children
McClaren, B., Martyn, M. M., Ince, J., Jan, A., Brown, N. J., Fahey, M. C., Crellin, E., & Gaff, C. (2025) · European Journal of Human Genetics · doi:10.1038/s41431-025-01864-3 · Cited by 12 · see citing works
Self-citationNovel treatments in epilepsy guided by genetic diagnosis
Marini, C., & Giardino, M. (2021) · British Journal of Clinical Pharmacology · doi:10.1111/bcp.15139 · Cited by 12 · see citing works
Real world outcomes and implementation pathways of exome sequencing in an adult genetic department
Walsh, M., West, K., Taylor, J., Thompson, B. A., Hopkins, A., Sexton, A., Ragunathan, A., Verma, K. P., Panetta, J., Matotek, E., et al. (2022) · Genetics in Medicine · doi:10.1016/j.gim.2022.03.010 · Cited by 12 · see citing works
Self-citationUnderstanding the Clinical Utility of Genome Sequencing in Critically Ill Newborns
Lantos, J. D., Brunelli, L., & Hayeems, R. Z. (2023) · The Journal of Pediatrics · doi:10.1016/j.jpeds.2023.113438 · Cited by 12 · see citing works
Liu, J., Yu, Z., Huang, J., Zhu, D., Zang, P., Luo, Z., Yang, Y., Peng, Y., Xiao, Z., Zhu, Y., et al. (2021) · Human Mutation · doi:10.1002/humu.24266 · Cited by 11 · see citing works
Self-citationExome and Genome Sequencing to Diagnose the Genetic Basis of Neonatal Hypotonia
Morton, S. U., Costain, G., French, C. E., Wakeling, E. L., Szuto, A., Christodoulou, J., Cohn, R. D., Darras, B. T., Wojcik, M. H., D’Gama, A. M., et al. (2024) · Neurology · doi:10.1212/wnl.0000000000210106 · Cited by 11 · see citing works
Self-citationChad, L., Anderson, J., Cagliero, D., Hayeems, R. Z., Ly, L. G., & Szuto, A. (2022) · Hospital Pediatrics · doi:10.1542/hpeds.2022-006654 · Cited by 11 · see citing works
Zhu, W., Wang, C., Mullapudi, N., Cao, Y., Li, L., Lo, I. F. M., Tsui, S. K., Chen, X., Lei, Y., & Gu, S. (2022) · npj Genomic Medicine · doi:10.1038/s41525-022-00344-7 · Cited by 11 · see citing works
Bouffler, S. E., Lee, L., Lynch, F., Martyn, M. M., Lynch, E. L., Macciocca, I., Curnow, L., McCorkell, G., Lunke, S., Chong, B., et al. (2023) · BMJ Open · doi:10.1136/bmjopen-2023-072999 · Cited by 11 · see citing works
Self-citationEichinger, J., Zimmermann, B. M., Elger, B. S., McLennan, S., Filges, I., & Koné, I. (2023) · European Journal of Human Genetics · doi:10.1038/s41431-023-01468-9 · Cited by 11 · see citing works
Heinken, A., Kouche, S. E., Guéant‐Rodriguez, R., & Guéant, J. (2023) · Metabolism · doi:10.1016/j.metabol.2023.155738 · Cited by 11 · see citing works
- Authors
- Australian Genomics Health Alliance Acute Care Flagship, Lunke, S., Eggers, S., Wilson, M., Patel, C., Barnett, C. P., Pinner, J., Sandaradura, S. A., Buckley, M. F., Krzesinski, E. I., de Silva, M. G., Brett, G. R., Boggs, K., Mowat, D., Kirk, E. P., Adès, L. C., Akesson, L. S., Amor, D. J., Ayres, S., Baxendale, A., Borrie, S., Bray, A., Brown, N. J., Chan, C. Y., Chong, B., Cliffe, C., Delatycki, M. B., Edwards, M., Elakis, G., Fahey, M. C., Fennell, A., Fowles, L., Gallacher, L., Higgins, M., Howell, K. B., Hunt, L., Hunter, M. F., Jones, K. J., King, S., Kumble, S., Lang, S., Le Moing, M., Ma, A., Phelan, D., Quinn, M. C. J., Richards, A., Richmond, C. M., Riseley, J., Rodgers, J., Sachdev, R., Sadedin, S., Schlapbach, L. J., Smith, J., Springer, A., Tan, N. B., Tan, T. Y., Temple, S. L., Theda, C., Vasudevan, A., White, S. M., Yeung, A., Zhu, Y., Martyn, M., Best, S., Roscioli, T., Christodoulou, J., & Stark, Z.
- Affiliations
- The University of Melbourne (AU)
- The University of Sydney (AU)
- Royal Brisbane and Women's Hospital (AU)
- Women's and Children's Hospital (AU)
- Monash Health (AU)
- Australian Genomics Health Alliance, Parkville, Australia
- Children's Hospital at Westmead (AU)
- UNSW Sydney (AU)
- Royal Children's Hospital (AU)
- Victorian Clinical Genetics Services (AU)
- Hunter Genetics (AU)
- The University of Queensland (AU)
- South Australia Pathology (AU)
- Victorian Clinical Genetics Services, Murdoch Children’s Research Institute, Melbourne, Australia
- Royal Women's Hospital (AU)
- Murdoch Children's Research Institute (AU)
- Corresponding author
- Stark, Zornitza
- ORCID
- Lunke, Sebastian
- Wilson, Meredith
- Patel, Chirag
- Barnett, Christopher P.
- Pinner, Jason
- Sandaradura, Sarah A.
- Buckley, Michael F.
- Krzesinski, Emma I.
- Brett, Gemma R.
- Mowat, David
- Kirk, Edwin P.
- Akesson, Lauren S.
- Amor, David J.
- Ayres, Samantha
- Bray, Alessandra
- Brown, Natasha J.
- Chan, Cheng Yee
- Chong, Belinda
- Cliffe, Corrina
- Delatycki, Martin B.
- Edwards, Matthew
- Fahey, Michael C.
- Fennell, Andrew
- Fowles, Lindsay
- Gallacher, Lyndon
- Higgins, Megan
- Howell, Katherine B.
- Hunt, Lauren
- Hunter, Matthew F.
- Jones, Kristi J.
- King, Sarah
- Kumble, Smitha
- Ma, Alan
- Phelan, Dean
- Quinn, Michael C. J.
- Richmond, Christopher M.
- Rodgers, Jonathan
- Sachdev, Rani
- Sadedin, Simon
- Schlapbach, Luregn J.
- Smith, Janine
- Springer, Amanda
- Tan, Natalie B.
- Tan, Tiong Y.
- Theda, Christiane
- Vasudevan, Anand
- White, Susan M.
- Yeung, Alison
- Zhu, Ying
- Martyn, Melissa
- Best, Stephanie
- Roscioli, Tony
- Christodoulou, John
- Stark, Zornitza
- Venue
- JAMA
- Publisher
- American Medical Association (AMA)
- Published
- 2020-06-23
- Volume
- 323
- Issue
- 24
- Pages
- 2503
- ISSN
- 0002-9955 (ISSN-L)
- 0098-7484
- PMC
- PMC7312414
- OpenAlex
- W3035821413
- Cited by
- 239
- References
- 27
- Citations by year
- 2026: 19 · 2025: 33 · 2024: 37 · 2023: 44 · 2022: 58 · 2021: 38 · 2020: 9 · 2019: 1
- FWCI
- 21.82
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- JAMA (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Zurich Open Repository and Archive (University of Zurich) (acceptedVersion)
- Adelaide Research & Scholarship (AR&S) (University of Adelaide) (submittedVersion)
- Griffith Research Online (submittedVersion, other-oa)
- Zurich Open Repository and Archive (University of Zurich) (submittedVersion)
- Zurich Open Repository and Archive (University of Zurich)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Connective tissue disorders research
- Keywords
- pediatric intensive care, genomic diagnostics, diagnostic yield, turnaround time, implementation strategies, clinical management change, mitochondrial genome sequencing, copy number analysis, neonatal intensive care, public health care system
- MeSH terms
- Exome Sequencing, Australia, Child, Child, Preschool, Feasibility Studies, Female, Genetic Testing, Humans, Infant, Infant, Newborn, Male, National Health Programs, Prospective Studies, Time Factors, Critical Illness, Genetic Diseases, Inborn
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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