The Sequencing Quality Control 2 study: establishing community standards for sequencing in precision medicine

Mercer, Tim R.; Xu, Joshua; Mason, Christopher E.; Tong, Weida

doi:10.1186/s13059-021-02528-3

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…We benchmarked DRAGEN on publicly available datasets from four cancer cell lines with curated truth sets [16, 19]. We chose the NYGC and SEQCII datasets because they were created and curated by third parties, to ensure an impartial assessment.…”

Section: Somatic Wgs T/n Resultsmentioning

confidence: 99%

Somatic small-variant calling methods in Illumina DRAGEN™ Secondary Analysis

Scheffler

Catreux

O’Connell

et al. 2023

Preprint

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We present the DRAGEN™ somatic pipeline for calling small somatic variants from tumor samples, with or without paired normal samples. The DRAGEN somatic variant caller offers 1) a flexible architecture that can be used on a wide array of somatic use cases; 2) built-in noise models enabling robustness against various sources of noise artifacts (mapping, genome context, or sample specific); 3) performance of joint analysis of tumor and normal samples in the case of a tumor-normal workflow yielding improved accuracy; 4) benefits from FPGA acceleration for efficient run time. We demonstrate the speed and accuracy of the DRAGEN tumor-normal pipeline across a range of whole genome sequencing (WGS) datasets and compare against third party tools such as Mutect2/GATK4 [1] and Strelka2 [2]. DRAGEN secondary analysis outperforms all other tools with its ability to complete a 110x/40x T/N whole-genome analysis in less than two hours. It offers exceptional accuracy, with higher sensitivity and precision than third party tools. We also show that the DRAGEN T/N workflow supports analysis of liquid and late-stage solid tumors by tolerating tumor-in-normal (TiN) contamination.

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Section: Somatic Wgs T/n Resultsmentioning

confidence: 99%

Somatic small-variant calling methods in Illumina DRAGEN™ Secondary Analysis

Scheffler

Catreux

O’Connell

et al. 2023

Preprint

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“…SEQC2 is a genome-sequencing quality control project led by the FDA in the United States to evaluate the inter-platform reproducibility of NGS technology and to establish best-practice recommendation [ 97 ]. Nevertheless, the sequencing procedures and analysis algorithms for GS and ES have not been well standardized.…”

Section: Discussionmentioning

confidence: 99%

Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities—A Narrative Review

Chen

2023

Children

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Unexplained global developmental delay (GDD) and intellectual disabilities (ID) together affect nearly 2% of the pediatric population. Establishing an etiologic diagnosis is crucial for disease management, prognostic evaluation, and provision of physical and psychological support for both the patient and the family. Advancements in genome sequencing have allowed rapid accumulation of gene–disorder associations and have accelerated the search for an etiologic diagnosis for unexplained GDD/ID. We reviewed recent studies that utilized genome-wide analysis technologies, and we discussed their diagnostic yield, strengths, and limitations. Overall, exome sequencing (ES) and genome sequencing (GS) outperformed chromosomal microarrays and targeted panel sequencing. GS provides coverage for both ES and chromosomal microarray regions, providing the maximal diagnostic potential, and the cost of ES and reanalysis of ES-negative results is currently still lower than that of GS alone. Therefore, singleton or trio ES is the more cost-effective option for the initial investigation of individuals with GDD/ID in clinical practice compared to a staged approach or GS alone. Based on these updated evidence, we proposed an evaluation algorithm with ES as the first-tier evaluation for unexplained GDD/ID.

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“…However, there is still no established reference for somatic variant calling. While the 1+ Million Genomes initiative [ 23 ] and the Somatic Mutation Working Group of the Sequencing Quality Control Phase II Consortium [ 24 ] have begun to address this building a community standard truth set of somatic variants remains a challenging task. Instead, in-house data comprising hundreds of manually curated somatic mutations must be reanalysed each time a new modality is implemented.…”

Section: Bioinformaticsmentioning

confidence: 99%

Whole genome sequencing in clinical practice

Bagger,

Borgwardt,

Jespersen

et al. 2024

BMC Med Genomics

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Whole genome sequencing (WGS) is becoming the preferred method for molecular genetic diagnosis of rare and unknown diseases and for identification of actionable cancer drivers. Compared to other molecular genetic methods, WGS captures most genomic variation and eliminates the need for sequential genetic testing. Whereas, the laboratory requirements are similar to conventional molecular genetics, the amount of data is large and WGS requires a comprehensive computational and storage infrastructure in order to facilitate data processing within a clinically relevant timeframe. The output of a single WGS analyses is roughly 5 MIO variants and data interpretation involves specialized staff collaborating with the clinical specialists in order to provide standard of care reports. Although the field is continuously refining the standards for variant classification, there are still unresolved issues associated with the clinical application. The review provides an overview of WGS in clinical practice - describing the technology and current applications as well as challenges connected with data processing, interpretation and clinical reporting.

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The Sequencing Quality Control 2 study: establishing community standards for sequencing in precision medicine

Cited by 11 publications

References 17 publications

Somatic small-variant calling methods in Illumina DRAGEN™ Secondary Analysis

Somatic small-variant calling methods in Illumina DRAGEN™ Secondary Analysis

Genome-Wide Sequencing Modalities for Children with Unexplained Global Developmental Delay and Intellectual Disabilities—A Narrative Review

Whole genome sequencing in clinical practice

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