Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review
NPJ Genom Med. 2024 Feb 27;9(1):17. doi: 10.1038/s41525-024-00404-0. ABSTRACT Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid genome sequencing (URGS), and rapid exome sequencing (RES) are diagnostic tests for genetic diseases for ICU patients. In 44 studies of […]
Evidence review and considerations for use of first line genome sequencing to diagnose rare genetic disorders
NPJ Genom Med. 2024 Feb 26;9(1):15. doi: 10.1038/s41525-024-00396-x. ABSTRACT Early use of genome sequencing (GS) in the diagnostic odyssey can reduce suffering and improve care, but questions remain about which patient populations are most amenable to GS as a first-line diagnostic test. To address this, the Medical Genome Initiative conducted a literature review to identify […]
Multi-center implementation of rapid whole genome sequencing provides additional evidence of its utility in the pediatric inpatient setting
Front Pediatr. 2024 Feb 19;12:1349519. doi: 10.3389/fped.2024.1349519. eCollection 2024. ABSTRACT OBJECTIVE: Multi-center implementation of rapid whole genome sequencing with assessment of the clinical utility of rapid whole genome sequencing (rWGS), including positive, negative and uncertain results, in admitted infants with a suspected genetic disease. STUDY DESIGN: rWGS tests were ordered at eight hospitals between November […]
Genome sequencing detects a wide range of clinically relevant copy number variants and other genomic alterations
Genet Med. 2023 Oct 20:101006. doi: 10.1016/j.gim.2023.101006. Online ahead of print. ABSTRACT PURPOSE: Copy number variants (CNVs) and other non-SNV/indel variant types contribute an important proportion of diagnoses in individuals with suspected genetic disease. This study describes the range of such variants detected by genome sequencing (GS). METHODS: For a pediatric cohort of 1032 participants […]
Rapid Whole-Genomic Sequencing and a Targeted Neonatal Gene Panel in Infants With a Suspected Genetic Disorder
JAMA. 2023 Jul 11;330(2):161-169. doi: 10.1001/jama.2023.9350. ABSTRACT IMPORTANCE: Genomic testing in infancy guides medical decisions and can improve health outcomes. However, it is unclear whether genomic sequencing or a targeted neonatal gene-sequencing test provides comparable molecular diagnostic yields and times to return of results. OBJECTIVE: To compare outcomes of genomic sequencing with those of a […]
Assessing Diversity in Newborn Genomic Sequencing Research Recruitment: Race/Ethnicity and Primary Spoken Language Variation in Eligibility, Enrollment, and Reasons for Declining
Clin Ther. 2023 Jul 8:S0149-2918(23)00220-5. doi: 10.1016/j.clinthera.2023.06.014. Online ahead of print. ABSTRACT PURPOSE: Diagnostic genomic research has the potential to directly benefit participants. This study sought to identify barriers to equitable enrollment of acutely ill newborns into a diagnostic genomic sequencing research study. METHODS: We reviewed the 16-month recruitment process of a diagnostic genomic research […]
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