Abstract：Pediatric patients in the neonatal intensive care unit (NICU) and the pediatric intensive care unit (PICU) have a high incidence rate of genetic diseases, and early rapid etiological diagnosis and targeted interventions can help to reduce mortality or improve prognosis. Whole-genome sequencing covers more comprehensive information including point mutation, copy number, and structural and rearrangement variations in the intron region and has become one of the powerful diagnostic tools for genetic diseases. Sequencing data require highly professional judgment and interpretation and are returned for clinical application after several weeks, which cannot meet the need for the diagnosis and treatment of genetic diseases in children. This article introduces the clinical application of rapid whole-genome sequencing in the NICU/PICU and briefly describes related techniques of artificial intelligence-rapid whole-genome sequencing diagnostic system, a rapid high-throughput automated platform for the diagnosis of genetic diseases. The diagnostic system introduces artificial intelligence into the processing of data after whole-genome sequencing and can solve the problems of long time and professional interpretation required for routine genome sequencing and provide a rapid diagnostic regimen for critically ill children suspected of genetic diseases within 24 hours, and therefore, it holds promise for clinical application.
LUO Fang,LI Hao-Min. Application of the artificial intelligence-rapid whole-genome sequencing diagnostic system in the neonatal/pediatric intensive care unit[J]. CJCP, 2021, 23(5): 433-437.
OMIM. OMIM entry statistics:number of entries in OMIM[EB/OL].[2021-03-03]. https://www.omim.org/statistics/entry.
[2]
Chong JX, Buckingham KJ, Jhangiani SN, et al. The genetic basis of mendelian phenotypes:discoveries, challenges, and opportunities[J]. Am J Hum Genet, 2015, 97(2):199-215.
[3]
Khokha MK, Mitchell LE, Wallingford JB. White paper on the study of birth defects[J]. Birth Defects Res, 2017, 109(2):180-185.
[4]
Murphy SL, Xu JQ, Kochanek KD, et al. Mortality in the United States, 2017[J]. NCHS Data Brief, 2018(328):1-8.
[5]
Savage L, Adams SD, James K, et al. Rapid whole-genome sequencing identifies a homozygous novel variant, His540Arg, in HSD17B4 resulting in D-bifunctional protein deficiency disorder diagnosis[J]. Cold Spring Harb Mol Case Stud, 2020, 6(6):a005496.
[6]
Hildreth A, Wigby K, Chowdhury S, et al. Rapid whole-genome sequencing identifies a novel homozygous NPC1 variant associated with Niemann-Pick type C1 disease in a 7-week-old male with cholestasis[J]. Cold Spring Harb Mol Case Stud, 2017, 3(5):a001966.
[7]
Saunders CJ, Miller NA, Soden SE, et al. Rapid whole-genome sequencing for genetic disease diagnosis in neonatal intensive care units[J]. Sci Transl Med, 2012, 4(154):154ra135.
[8]
Miller NA, Farrow EG, Gibson M, et al. A 26-hour system of highly sensitive whole genome sequencing for emergency management of genetic diseases[J]. Genome Med, 2015, 7:100.
[9]
Clark MM, Hildreth A, Batalov S, et al. Diagnosis of genetic diseases in seriously ill children by rapid whole-genome sequencing and automated phenotyping and interpretation[J]. Sci Transl Med, 2019, 11(489):eaat6177.
[10]
Willig LK, Petrikin JE, Smith LD, et al. Whole-genome sequencing for identification of Mendelian disorders in critically ill infants:a retrospective analysis of diagnostic and clinical findings[J]. Lancet Respir Med, 2015, 3(5):377-387.
[11]
Petrikin JE, Cakici JA, Clark MM, et al. The NSIGHT1-randomized controlled trial:rapid whole-genome sequencing for accelerated etiologic diagnosis in critically ill infants[J]. NPJ Genom Med, 2018, 3:6.
[12]
Sanford EF, Clark MM, Farnaes L, et al. Rapid whole genome sequencing has clinical utility in children in the PICU[J]. Pediatr Crit Care Med, 2019, 20(11):1007-1020.
[13]
Mestek-Boukhibar L, Clement E, Jones WD, et al. Rapid Paediatric Sequencing (RaPS):comprehensive real-life workflow for rapid diagnosis of critically ill children[J]. J Med Genet, 2018, 55(11):721-728.
[14]
Kernan KF, Ghaloul-Gonzalez L, Vockley J, et al. Rapid whole genome sequencing and fulfilling the promise of precision pediatric critical care[J]. Pediatr Crit Care Med, 2019, 20(11):1085-1086.
[15]
Farnaes L, Hildreth A, Sweeney NM, et al. Rapid whole-genome sequencing decreases infant morbidity and cost of hospitalization[J]. NPJ Genom Med, 2018, 3:10.
[16]
Petrikin JE, Willig LK, Smith LD, et al. Rapid whole genome sequencing and precision neonatology[J]. Semin Perinatol, 2015, 39(8):623-631.
[17]
Son JH, Xie GC, Yuan C, et al. Deep phenotyping on electronic health records facilitates genetic diagnosis by clinical exomes[J]. Am J Hum Genet, 2018, 103(1):58-73.
[18]
Wei WQ, Denny JC. Extracting research-quality phenotypes from electronic health records to support precision medicine[J]. Genome Med, 2015, 7(1):41.
[19]
Dhombres F, Bodenreider O. Interoperability between phenotypes in research and healthcare terminologies-Investigating partial mappings between HPO and SNOMED CT[J]. J Biomed Semantics, 2016, 7:3.
[20]
Kingsmore SF, Cakici JA, Clark MM, et al. A randomized, controlled trial of the analytic and diagnostic performance of singleton and trio, rapid genome and exome sequencing in ill infants[J]. Am J Hum Genet, 2019, 105(4):719-733.
[21]
Bell SG. Ethical implications of rapid whole-genome sequencing in neonates[J]. Neonatal Netw, 2018, 37(1):42-44.
[22]
Cakici JA, Dimmock DP, Caylor SA, et al. A prospective study of parental perceptions of rapid whole-genome and -exome sequencing among seriously ill infants[J]. Am J Hum Genet, 2020, 107(5):953-962.
[23]
Dimmock DP, Clark MM, Gaughran M, et al. An RCT of rapid genomic sequencing among seriously ill infants results in high clinical utility, changes in management, and low perceived harm[J]. Am J Hum Genet, 2020, 107(5):942-952.
