Dataset Information

Integrated multi-omics for rapid rare disease diagnosis on a national scale

ABSTRACT: The Australian Acute Care Genomics program provides ultra-rapid diagnostic testing to critically ill infants and children with suspected genetic conditions. Over two years, we performed whole genome sequencing (WGS) in 290 families, with average time to result of 2.9 days, and diagnostic yield of 47%. We performed additional bioinformatic analyses and transcriptome sequencing in all patients who remained undiagnosed. Long-read sequencing and functional assays, ranging from clinically accredited enzyme analysis to bespoke quantitative proteomics, were deployed in selected cases. This resulted in an additional 19 diagnoses, and an overall diagnostic yield of 54%. Diagnostic variants ranged from structural chromosomal abnormalities through to an intronic retrotransposon, disrupting splicing. Critical care management changed in 120 diagnosed patients (77%). Results informed precision treatments; surgical and transplant decisions; and palliation in 94 (60%). We propose that integration of multi-omic approaches into mainstream diagnostic practice is necessary to realise the full potential of genomic testing.

INSTRUMENT(S): Orbitrap Eclipse

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Primary Cell, Fibroblast

DISEASE(S): Developmental And Epileptic Encephalopathy 9

SUBMITTER: David Stroud

LAB HEAD: David Stroud

PROVIDER: PXD042001 | Pride | 2023-10-24

REPOSITORIES: Pride

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			Action	DRS
	220818_LS-4771_Control_1.raw	Raw
	220818_LS-4771_Control_2.raw	Raw
	220818_LS-4771_Control_3.raw	Raw
	220818_LS-4771_Control_4.raw	Raw
	220818_LS-4771_Control_5.raw	Raw

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Integrated multi-omics for rapid rare disease diagnosis on a national scale.

Lunke Sebastian S Bouffler Sophie E SE Patel Chirag V CV Sandaradura Sarah A SA Wilson Meredith M Pinner Jason J Hunter Matthew F MF Barnett Christopher P CP Wallis Mathew M Kamien Benjamin B Tan Tiong Y TY Freckmann Mary-Louise ML Chong Belinda B Phelan Dean D Francis David D Kassahn Karin S KS Ha Thuong T Gao Song S Arts Peer P Jackson Matilda R MR Scott Hamish S HS Eggers Stefanie S Rowley Simone S Boggs Kirsten K Rakonjac Ana A Brett Gemma R GR de Silva Michelle G MG Springer Amanda A Ward Michelle M Stallard Kirsty K Simons Cas C Conway Thomas T Halman Andreas A Van Bergen Nicole J NJ Sikora Tim T Semcesen Liana N LN Stroud David A DA Compton Alison G AG Thorburn David R DR Bell Katrina M KM Sadedin Simon S North Kathryn N KN Christodoulou John J Stark Zornitza Z

Nature medicine 20230608 7

Critically ill infants and children with rare diseases need equitable access to rapid and accurate diagnosis to direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing to 290 families whose critically ill infants and children were admitted to hospitals throughout Australia with suspected genetic conditions. The average time to result was 2.9 d and diagnostic yield was 47%. We performed additional bioinformatic analyses and transcriptome sequenci ...[more]

PMID: 37291213

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