Rapid Whole Genome Sequencing for Diagnosis of Single Locus Genetic Diseases in Critically Ill Children
Methods Mol Biol. 2023;2621:217-239. doi: 10.1007/978-1-0716-2950-5_12. ABSTRACT Upon admission to intensive care units (ICU), the differential diagnosis of almost all infants with diseases of unclear etiology includes single locus genetic diseases. Rapid whole genome sequencing (rWGS), including sample preparation, short-read sequencing-by-synthesis, informatics pipelining, and semiautomated interpretation, can now identify nucleotide and structural variants associated with […]
Automated prioritization of sick newborns for whole genome sequencing using clinical natural language processing and machine learning
Genome Med. 2023 Mar 16;15(1):18. doi: 10.1186/s13073-023-01166-7. ABSTRACT BACKGROUND: Rapidly and efficiently identifying critically ill infants for whole genome sequencing (WGS) is a costly and challenging task currently performed by scarce, highly trained experts and is a major bottleneck for application of WGS in the NICU. There is a dire need for automated means to […]
Genomic sequencing has a high diagnostic yield in children with congenital anomalies of the heart and urinary system
Front Pediatr. 2023 Mar 14;11:1157630. doi: 10.3389/fped.2023.1157630. eCollection 2023. ABSTRACT BACKGROUND: Congenital heart defects (CHD) and congenital anomalies of the kidney and urinary tract (CAKUT) account for significant morbidity and mortality in childhood. Dozens of monogenic causes of anomalies in each organ system have been identified. However, even though 30% of CHD patients also have […]
Artificial Intelligence in the Genetic Diagnosis of Rare Disease
Clin Lab Med. 2023 Mar;43(1):127-143. doi: 10.1016/j.cll.2022.09.023. Part of special issue: Artificial Intelligence in the Clinical Laboratory: Current Practice and Emerging Opportunities PMID:36764805 DOI:10.1016/j.cll.2022.09.023
Scalable, high quality, whole genome sequencing from archived, newborn, dried blood spots
NPJ Genom Med. 2023 Feb 14;8(1):5. doi: 10.1038/s41525-023-00349-w. ABSTRACT Universal newborn screening (NBS) is a highly successful public health intervention. Archived dried bloodspots (DBS) collected for NBS represent a rich resource for population genomic studies. To fully harness this resource in such studies, DBS must yield high-quality genomic DNA (gDNA) for whole genome sequencing (WGS). […]
25: A Multicenter Cohort Analysis of Rapid Genome Sequencing in the PICU
Critical Care Medicine 51(1):p 13, January 2023. Genetic disorders contribute significantly to morbidity and mortality in pediatric critical care. Diagnostic rapid whole genome sequencing (rWGS) has dramatically impacted care in neonatal intensive care units (ICU). There remains a population of undiagnosed patients with rare genetic diseases who present critically ill to the pediatric ICU (PICU) […]
Insights into the perinatal phenotype of Kabuki syndrome in infants identified by genome-wide sequencing
Am J Med Genet A. 2023 Jan 18. doi: 10.1002/ajmg.a.63097. Online ahead of print. ABSTRACT Increasing use of unbiased genomic sequencing in critically ill infants can expand understanding of rare diseases such as Kabuki syndrome (KS). Infants diagnosed with KS through genome-wide sequencing performed during the initial hospitalization underwent retrospective review of medical records. Human […]
Breaking Barriers to Rapid Whole Genome Sequencing in Pediatrics: Michigan’s Project Baby Deer
Children. 2023; 10(1):106. https://doi.org/10.3390/children10010106 ABSTRACT The integration of precision medicine in the care of hospitalized children is ever evolving. However, access to new genomic diagnostics such as rapid whole genome sequencing (rWGS) is hindered by barriers in implementation. Michigan’s Project Baby Deer (PBD) is a multi-center collaborative effort that sought to break down barriers to […]
Rapid Whole Genome Sequencing in Critically Ill Neonates Enables Precision Medicine Pipeline
J Pers Med. 2022 Nov 18;12(11):1924. doi: 10.3390/jpm12111924. ABSTRACT Rapid genome sequencing in critically ill infants is increasingly identified as a crucial test for providing targeted and informed patient care. We report the outcomes of a pilot study wherein eight critically ill neonates received rapid whole genome sequencing with parental samples in an effort to […]
An automated 13.5 hour system for scalable diagnosis and acute management guidance for genetic diseases
Nat Commun. 2022 Jul 26;13(1):4057. doi: 10.1038/s41467-022-31446-6. While many genetic diseases have effective treatments, they frequently progress rapidly to severe morbidity or mortality if those treatments are not implemented immediately. Since front-line physicians frequently lack familiarity with these diseases, timely molecular diagnosis may not improve outcomes. Herein we describe Genome-to-Treatment, an automated, virtual system for […]