Ultrarapid Nanopore Genome Sequencing in a Critical Care Setting

Gorzynski, John E.; Goenka, Sneha D.; Shafin, Kishwar; Jensen, Tanner D.; Fisk, Dianna G.; Grove, Megan E.; Spiteri, Elizabeth; Pesout, Trevor; Monlong, Jean; Baid, Gunjan; Bernstein, Jonathan A.; Ceresnak, Scott R.; Chang, Pi-Chuan; Christle, Jeffrey W.; Chubb, Henry; Dalton, Karen; Dunn, Kyla; Garalde, Daniel R.; Guillory, Joseph; Knowles, Joshua W.; Kolesnikov, Alexey; Ma, Michael; Moscarello, Tia; Nattestad, Maria; Pérez, Marco; Ruzhnikov, Maura R.Z.; Samadi, Mehrzad; Setia, Ankit; Wright, Chris; Wusthoff, Courtney J.; Xiong, Katherine; Zhu, Tong; Jain, Miten; Sedlazeck, Fritz J.; Carroll, Andrew; Paten, Benedict; Ashley, Euan A.

doi:10.1056/nejmc2112090

Cited by 136 publications

(119 citation statements)

References 4 publications

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“…DRAGEN implements FPGA (Field Programmable Gate Array) technology, an alternative to conventional CPU-based systems to expedite the execution of genome pipelines. Recently, some groups have demonstrated record-breaking fast implementation of GS using optimized SR/LR sequencing, DRAGEN/multiple cloud computing machines, and semi-automated downstream analysis to diagnose children with suspected Mendelian disorder, who were critically ill and admitted to ICU (fastest, 7 h, 18 min) [292,293].…”

Section: Automated Re-analysismentioning

confidence: 99%

A guide for the diagnosis of rare and undiagnosed disease: beyond the exome

2022

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Rare diseases affect 30 million people in the USA and more than 300–400 million worldwide, often causing chronic illness, disability, and premature death. Traditional diagnostic techniques rely heavily on heuristic approaches, coupling clinical experience from prior rare disease presentations with the medical literature. A large number of rare disease patients remain undiagnosed for years and many even die without an accurate diagnosis. In recent years, gene panels, microarrays, and exome sequencing have helped to identify the molecular cause of such rare and undiagnosed diseases. These technologies have allowed diagnoses for a sizable proportion (25–35%) of undiagnosed patients, often with actionable findings. However, a large proportion of these patients remain undiagnosed. In this review, we focus on technologies that can be adopted if exome sequencing is unrevealing. We discuss the benefits of sequencing the whole genome and the additional benefit that may be offered by long-read technology, pan-genome reference, transcriptomics, metabolomics, proteomics, and methyl profiling. We highlight computational methods to help identify regionally distant patients with similar phenotypes or similar genetic mutations. Finally, we describe approaches to automate and accelerate genomic analysis. The strategies discussed here are intended to serve as a guide for clinicians and researchers in the next steps when encountering patients with non-diagnostic exomes.

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Section: Automated Re-analysismentioning

confidence: 99%

A guide for the diagnosis of rare and undiagnosed disease: beyond the exome

2022

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“…Author details 1 Department of Computer Science and Engineering, University of Michigan, Ann Arbor, USA. 2 NVIDIA Corporation, Santa Clara, USA.…”

Section: Competing Interestsmentioning

confidence: 99%

“…This helps applications like denovo assembly and structural variant calling [1, 3]. A recent study used long read sequencing to showcase the world’s fastest blood to variants workflow for genetic diagnosis at the point-of-care [2]. This further underlines the emerging significance of long read sequencing.…”

Section: Introductionmentioning

confidence: 99%

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Accelerating Minimap2 for accurate long read alignment on GPUs

Sadasivan

Maric

Dawson

et al. 2022

Preprint

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BACKGROUND: Long read sequencing technology is becoming increasingly popular for Precision Medicine applications like variant calling from Whole Genome Sequencing (WGS) and for metagenomics applications like microbial abundance estimation. Minimap2 is the state-of-the-art aligner and mapper used by the leading long read sequencing technologies, today. However, Minimap2 is very slow for long noisy reads. 60-70% of the run-time on a CPU comes from the highly sequential chaining step in Minimap2. Most Point-of-Care computational workflows in long read sequencing use Graphics Processing Units (GPUs). We present minimap2-accelerated (mm2-ax), a heterogeneous design for sequence mapping and alignment where the compute intensive chaining step of minimap2 is sped up on the GPU and demonstrate its time and cost benefits. RESULTS: We extract better intra-read parallelism from chaining without loosing mapping accuracy by forward transforming Minimap2's chaining algorithm . Further, we utilize the high memory available on modern cloud instances for better performance on the GPU by converting a sparse vector which defines the chaining workload to a dense one in order to optimize for better arithmetic intensity (more operations per byte of data fetched from high-latency global memory) on the GPU. We also optimize for better workload balancing, data locality and minimal branch divergence on the GPU. We show mm2-ax on an NVIDIA A100 GPU improves the chaining step with 12.6-5X Speedup and 9.44-3.77X Speedup:Costup over the fastest version of Minimap2, mm2-fast, benchmarked on a single Google Cloud Platform instance of 30 SIMD cores (Intel Cascade Lake with AVX-512).

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“…How often does the plan to await some test results roll over from one ward round to the next? A team at Stanford University collaborating with Google shows that it doesn’t have to be that way, even if you’re awaiting genetic sequencing that usually takes weeks 3. Twelve patients in critical care with a clinical presentation consistent with a genetic disease were selected to pilot ultrarapid nanopore genome sequencing.…”

Section: Gene Geniementioning

confidence: 99%

Tom Nolan's research reviews—20 January 2022

Nolan¹

2022

BMJ

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Ultrarapid Nanopore Genome Sequencing in a Critical Care Setting

Cited by 136 publications

References 4 publications

A guide for the diagnosis of rare and undiagnosed disease: beyond the exome

A guide for the diagnosis of rare and undiagnosed disease: beyond the exome

Accelerating Minimap2 for accurate long read alignment on GPUs

Tom Nolan's research reviews—20 January 2022

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