“Ultra-Rapid Nanopore Genome Sequencing in a Critical Care Setting”, John E. Gorzynski, Sneha D. Goenka, Kishwar Shafin, Tanner D. Jensen, Dianna G. Fisk, Megan E. Grove, Elizabeth Spiteri, Trevor Pesout, Jean Monlong, Gunjan Baid, Jonathan A. Bernstein, Scott Ceresnak, Pi-Chuan Chang, Jeffrey W. Christle, Henry Chubb, Karen P. Dalton, Kyla Dunn, Daniel R. Garalde, Joseph Guillory, Joshua W. Knowles, Alexey Kolesnikov, Michael Ma, Tia Moscarello, Maria Nattestad, Marco Perez, Maura R. Z. Ruzhnikov, Mehrzad Samadi, Ankit Setia, Chris Wright, Courtney J. Wusthoff, Katherine Xiong, Tong Zhu, Miten Jain, Fritz J. Sedlazeck, Andrew Carroll, Benedict Paten, Euan A. Ashley2022-01-12 (rare mutations, genome sequencing; similar)⁠:

[Using long read whole genome sequencing, we have broken the record for making the fastest genetic diagnosis—multiple times. Our fastest: 7hrs18min.

The new method published today has the potential to revolutionize diagnosing critically ill patients.

Our team…aimed to make fast/accurate genetic diagnoses using nanopore WGS optimized sample prep and loading 48 Oxford PomethION flow cells; created a pipeline to transfer data to the cloud, base call, and align in real time; optimized PEPPER-Margin-DeepVariant to quickly call variants; and the rest of the curation team customized a variant filtration schema that was not only fast, but reduced the list of variants for manual curation substantially, while still maintaining sensitivity…In some cases our average sequencing rate exceeded 1.8gb/min—a 1× genome in 1min45sec—unprecedented speed! One case was sequenced so fast that we set a Guinness World Record for the fastest DNA sequencing technique.

We then recruited 12 critically ill patients and sequenced their genomes to ~50×. The patients ranged in age from 3 months to 57 years and had clinical presentations including neurological/seizure disorders, sudden cardiac arrests, and severe heart failure. In 5 cases we identified genetics variants (SNPs and INDELs) in gene such as RYR2, TNNT2, PCDH19, and CSNK2B that explained the patient’s clinical signs. These findings led to definitive genetic diagnosis.

As a result, these patients received precision care weeks earlier than had they had standard genetic testing. Treatments included surgical interventions, a heart transplant, changes to their medicines, and family screening.]

[Google blogpost]

See Also:

• “Rapid Sequencing-Based Diagnosis of Thiamine Metabolism Dysfunction Syndrome”

• “Whole-genome sequencing of rare disease patients in a national healthcare system”

• “Whole-exome imputation within UK Biobank powers rare coding variant association and fine-mapping analyses”

• “Medical consequences of pathogenic CNVs in adults: analysis of the UK Biobank”

• “Quantifying the impact of rare and ultra-rare coding variation across the phenotypic spectrum”

• “Prevalence and architecture of de novo mutations in developmental disorders”

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