Scientific discovery in the age of artificial intelligence

Nature, Год журнала: 2023, Номер 620(7972), С. 47 - 60

Опубликована: Авг. 2, 2023

Язык: Английский

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Detection of mosaic and population-level structural variants with Sniffles2

Nature Biotechnology, Год журнала: 2024, Номер 42(10), С. 1571 - 1580

Опубликована: Янв. 2, 2024

Abstract Calling structural variations (SVs) is technically challenging, but using long reads remains the most accurate way to identify complex genomic alterations. Here we present Sniffles2, which improves over current methods by implementing a repeat aware clustering coupled with fast consensus sequence and coverage-adaptive filtering. Sniffles2 11.8 times faster 29% more than state-of-the-art SV callers across different coverages (5–50×), sequencing technologies (ONT HiFi) types. Furthermore, solves problem of family-level population-level calling produce fully genotyped VCF files. Across 11 probands, accurately identified causative SVs around MECP2 , including highly alleles three overlapping SVs. also enables detection mosaic in bulk long-read data. As result, multiple brain tissue from patient system atrophy. The showed remarkable diversity within cingulate cortex, impacting both genes involved neuron function repetitive elements.

Язык: Английский

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Comprehensive Structural Variant Detection: From Mosaic to Population-Level

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown

Опубликована: Апрель 5, 2022

Abstract Long-read Structural Variation (SV) calling remains a challenging but highly accurate way to identify complex genomic alterations. Here, we present Sniffles2, which is faster and more than state-of-the-art SV caller across different coverages, sequencing technologies, types. Furthermore, Sniffles2 solves the problem of family- population-level produce fully genotyped VCF files by introducing gVCF file concept. Across 11 probands, accurately identified causative SVs around MECP2 , including alleles with three overlapping SVs. also enables detection mosaic in bulk long-read data. As result, successfully multiple system atrophy patient brain. The showed remarkable diversity within cingulate cortex, impacting both genes involved neuron function repetitive elements. In summary, demonstrate utility versatility from population levels.

Язык: Английский

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Genomics in the long-read sequencing era

Trends in Genetics, Год журнала: 2023, Номер 39(9), С. 649 - 671

Опубликована: Май 23, 2023

Язык: Английский

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

Nature Medicine, Год журнала: 2023, Номер 29(7), С. 1681 - 1691

Опубликована: Июнь 8, 2023

Critically ill infants and children with rare diseases need equitable access to rapid accurate diagnosis direct clinical management. Over 2 years, the Acute Care Genomics program provided whole-genome sequencing 290 families whose critically were admitted hospitals throughout Australia suspected genetic conditions. The average time result was 2.9 d diagnostic yield 47%. We performed additional bioinformatic analyses transcriptome in all patients who remained undiagnosed. Long-read functional assays, ranging from clinically accredited enzyme analysis bespoke quantitative proteomics, deployed selected cases. This resulted an 19 diagnoses overall of 54%. Diagnostic variants ranged structural chromosomal abnormalities through intronic retrotransposon, disrupting splicing. Critical care management changed 120 diagnosed (77%). included major impacts, such as informing precision treatments, surgical transplant decisions palliation, 94 (60%). Our results provide preliminary evidence utility integrating multi-omic approaches into mainstream practice fully realize potential disease genomic testing a timely manner.

Язык: Английский

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Utility of long-read sequencing for All of Us

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Янв. 29, 2024

The All of Us (AoU) initiative aims to sequence the genomes over one million Americans from diverse ethnic backgrounds improve personalized medical care. In a recent technical pilot, we compare performance traditional short-read sequencing with long-read in small cohort samples HapMap project and two AoU control representing eight datasets. Our analysis reveals substantial differences ability these technologies accurately complex medically relevant genes, particularly terms gene coverage pathogenic variant identification. We also consider advantages challenges using low increase sample numbers large analysis. results show that HiFi reads produce most accurate for both variants. Further, present cloud-based pipeline optimize SNV, indel SV calling at scale long-reads These lead widespread improvements across AoU.

Язык: Английский

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Real-time genomic surveillance for enhanced control of infectious diseases and antimicrobial resistance

Frontiers in Science, Год журнала: 2024, Номер 2

Опубликована: Апрель 25, 2024

This article advocates for mobilizing pathogen genomic surveillance to contain and mitigate health threats from infectious diseases antimicrobial resistance (AMR), building upon successes achieved by large-scale genome sequencing analysis of SARS-CoV-2 variants in guiding COVID-19 monitoring public responses adopting a One Health approach. Capabilities laboratory-based epidemic alert systems should be enhanced fostering (i) universal access real-time whole sequence (WGS) data pathogens inform clinical practice, infection control, policies, vaccine drug research development; (ii) integration diagnostic microbiology data, testing asymptomatic individuals, epidemiological into programs; (iii) stronger cross-sectorial collaborations between healthcare, health, animal environmental using approaches, toward understanding the ecology transmission pathways AMR across ecosystems; (iv) international collaboration interconnection networks, harmonization laboratory methods, standardization methods global reporting, including on variant or strain nomenclature; (v) responsible sharing databases, platforms according FAIR (findability, accessibility, interoperability, reusability) principles; (vi) system implementation its cost-effectiveness different settings. Regional policies governance initiatives foster concerted development efficient utilization protect humans, animals, environment.

Язык: Английский

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Rapid genomic sequencing for genetic disease diagnosis and therapy in intensive care units: a review

npj Genomic Medicine, Год журнала: 2024, Номер 9(1)

Опубликована: Фев. 27, 2024

Abstract Single locus (Mendelian) diseases are a leading cause of childhood hospitalization, intensive care unit (ICU) admission, mortality, and healthcare cost. Rapid genome sequencing (RGS), ultra-rapid (URGS), rapid exome (RES) diagnostic tests for genetic ICU patients. In 44 studies children in ICUs with unknown etiology, 37% received diagnosis, 26% had consequent changes management, net costs were reduced by $14,265 per child tested URGS, RGS, or RES. URGS outperformed RGS RES faster time to higher rate diagnosis clinical utility. Diagnostic outcomes will improve as methods evolve, decrease, testing is implemented within precision medicine delivery systems attuned needs. currently performed <5% the ~200,000 likely benefit annually due lack payor coverage, inadequate reimbursement, hospital policies, hospitalist unfamiliarity, under-recognition possible diseases, current formatting rather than system. The gap between actual optimal increasing since expanded use lags growth those through new therapies. There sufficient evidence conclude that should be considered all uncertain etiology at admission. Minimally, ordered early during admissions critically ill infants suspected diseases.

Язык: Английский

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The Current State of Nanopore Sequencing

Methods in molecular biology, Год журнала: 2023, Номер unknown, С. 3 - 14

Опубликована: Янв. 1, 2023

Язык: Английский

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The Application of Long-Read Sequencing to Cancer

Cancers, Год журнала: 2024, Номер 16(7), С. 1275 - 1275

Опубликована: Март 25, 2024

Cancer is a multifaceted disease arising from numerous genomic aberrations that have been identified as result of advancements in sequencing technologies. While next-generation (NGS), which uses short reads, has transformed cancer research and diagnostics, it limited by read length. Third-generation (TGS), led the Pacific Biosciences Oxford Nanopore Technologies platforms, employs long-read sequences, marked paradigm shift research. genomes often harbour complex events, TGS, with its ability to span large regions, facilitated their characterisation, providing better understanding how rearrangements affect initiation progression. TGS also characterised entire transcriptome various cancers, revealing cancer-associated isoforms could serve biomarkers or therapeutic targets. Furthermore, advanced improving genome assemblies, detecting variants, more complete picture transcriptomes epigenomes. This review focuses on growing role We investigate advantages limitations, rigorous scientific analysis use previously hidden missed NGS. promising technology holds immense potential for both clinical applications, far-reaching implications diagnosis treatment.

Язык: Английский

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