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

S Lunke; SE Bouffler; CV Patel; SA Sandaradura; M Wilson; J Pinner; MF Hunter; CP Barnett; M Wallis; B Kamien; TY Tan; ML Freckmann; B Chong; D Phelan; D Francis; KS Kassahn; T Ha; S Gao; P Arts; MR Jackson; HS Scott; S Eggers; S Rowley; K Boggs; A Rakonjac; GR Brett; MG de Silva; A Springer; M Ward; K Stallard; C Simons; T Conway; A Halman; NJ Van Bergen; T Sikora; LN Semcesen; DA Stroud; AG Compton; DR Thorburn; KM Bell; S Sadedin; KN North; J Christodoulou; Z Stark

Journal article

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

S Lunke, SE Bouffler, CV Patel, SA Sandaradura, M Wilson, J Pinner, MF Hunter, CP Barnett, M Wallis, B Kamien, TY Tan, ML Freckmann, B Chong, D Phelan, D Francis, KS Kassahn, T Ha, S Gao, P Arts, MR Jackson Show all

Nature Medicine | NATURE PORTFOLIO | Published : 2023

DOI: 10.1038/s41591-023-02401-9

Abstract

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 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 selecte..

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University of Melbourne Researchers

Sebastian Lunke Author

Tiong Yang Tan Author

Andreas Halman Author

Nicole van Bergen Author

Grants

Awarded by State Government of Victoria

Funding Acknowledgements

We thank all the families who participated in this study and the clinical teams involved in their care. The Acute Care Genomics program was funded by the Medical Research Futures Fund, Genomics Health Futures Mission (GHFM76747; to Z.S.), Royal Children's Hospital Foundation grant (2020-1259; to Z.S.) and Queensland Genomics (to C.P.). In-kind support was provided by Australian Genomics (National Health and Medical Research Council grants GNT1113531 and GNT2000001; to K.N.N.) and the Sydney Children's Hospital Network (to M.W.). This research was supported by grants and fellowships from the Australian National Health and Medical Research Council (GNT2009732 and GNT1164479). We acknowledge the Mito Foundation and Bio21 Mass Spectrometry and Proteomics Facility for the provision of instrumentation, training and technical support. L.S. is supported by a Melbourne International Research Scholarship and the Mito Foundation PhD Top-up Scholarship. The research conducted at the Murdoch Children's Research Institute was supported by the Victorian Government's Operational Infrastructure Support Program. The Chair in Genomic Medicine awarded to J.C. is generously supported by The Royal Children's Hospital Foundation. The map used in Fig. 2a was sourced under a Pro Content license from canva.com. Icons used in Fig. 2b were sourced under a royalty-free license from thenounproject.com.