NDLI: Test development, optimization and validation of a WGS pipeline for genetic disorders

Content Provider	Springer Nature : BioMed Central
Author	Yang, Ziying Yang, Xu Sun, Yan Wang, Yaoshen Song, Lijie Qiao, Zhihong Fang, Zhonghai Wang, Zhonghua Liu, Lipei Chen, Yunmei Yan, Saiying Guo, Xueqin Zhang, Junqing Fan, Chunna Liu, Fengxia Peng, Zhiyu Peng, Huanhuan Sun, Jun Chen, Wei
Abstract	Background With advances in massive parallel sequencing (MPS) technology, whole-genome sequencing (WGS) has gradually evolved into the first-tier diagnostic test for genetic disorders. However, deployment practice and pipeline testing for clinical WGS are lacking. Methods In this study, we introduced a whole WGS pipeline for genetic disorders, which included the entire process from obtaining a sample to clinical reporting. All samples that underwent WGS were constructed using polymerase chain reaction (PCR)-free library preparation protocols and sequenced on the MGISEQ-2000 platform. Bioinformatics pipelines were developed for the simultaneous detection of various types of variants, including single nucleotide variants (SNVs), insertions and deletions (indels), copy number variants (CNVs) and balanced rearrangements, mitochondrial (MT) variants, and other complex variants such as repeat expansion, pseudogenes and absence of heterozygosity (AOH). A semiautomatic pipeline was developed for the interpretation of potential SNVs and CNVs. Forty-five samples (including 14 positive commercially available samples, 23 laboratory-held positive cell lines and 8 clinical cases) with known variants were used to validate the whole pipeline. Results In this study, a whole WGS pipeline for genetic disorders was developed and optimized. Forty-five samples with known variants (6 with SNVs and Indels, 3 with MT variants, 5 with aneuploidies, 1 with triploidy, 23 with CNVs, 5 with balanced rearrangements, 2 with repeat expansions, 1 with AOHs, and 1 with exon 7–8 deletion of SMN1 gene) validated the effectiveness of our pipeline. Conclusions This study has been piloted in test development, optimization, and validation of the WGS pipeline for genetic disorders. A set of best practices were recommended using our pipeline, along with a dataset of positive samples for benchmarking.
Related Links	https://bmcmedgenomics.biomedcentral.com/counter/pdf/10.1186/s12920-023-01495-x.pdf
Ending Page	11
Page Count	11
Starting Page	1
File Format	HTM / HTML
ISSN	17558794
DOI	10.1186/s12920-023-01495-x
Journal	BMC Medical Genomics
Issue Number	1
Volume Number	16
Language	English
Publisher	BioMed Central
Publisher Date	2023-04-05
Access Restriction	Open
Subject Keyword	Human Genetics Microarrays Gene Expression Whole genome sequencing Genetic disorders Clinical diagnosis Bioinformatics pipelines
Content Type	Text
Resource Type	Article
Subject	Genetics (clinical) Genetics
Journal Impact Factor	2.1/2023
5-Year Journal Impact Factor	2.5/2023

Sl.	Authority	Responsibilities	Communication Details
1	Ministry of Education (GoI), Department of Higher Education	Sanctioning Authority	https://www.education.gov.in/ict-initiatives
2	Indian Institute of Technology Kharagpur	Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project	https://www.iitkgp.ac.in
3	National Digital Library of India Office, Indian Institute of Technology Kharagpur	The administrative and infrastructural headquarters of the project	Dr. B. Sutradhar bsutra@ndl.gov.in
4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
5	Website/Portal (Helpdesk)	Queries regarding NDLI and its services	support@ndl.gov.in
6	Contents and Copyright Issues	Queries related to content curation and copyright issues	content@ndl.gov.in
7	National Digital Library of India Club (NDLI Club)	Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach	clubsupport@ndl.gov.in
8	Digital Preservation Centre (DPC)	Assistance with digitizing and archiving copyright-free printed books	dpc@ndl.gov.in
9	IDR Setup or Support	Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops	idr@ndl.gov.in

Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders

Whole-exome sequencing enables rapid and prenatal diagnosis of inherited skin disorders

Whole genome sequencing in clinical practice

Validation of whole genome sequencing from dried blood spots

Whole genome sequencing in the diagnosis of primary ciliary dyskinesia

Establishment and genetically characterization of patient-derived xenograft models of cervical cancer

A clinically validated whole genome pipeline for structural variant detection and analysis

Whole-genome sequencing, as a powerful diagnostic tool in hearing loss, reveals novel variants in PTPRQ missed by whole-exome sequencing

Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data

Test development, optimization and validation of a WGS pipeline for genetic disorders

Similar Documents

Characterizing sensitivity and coverage of clinical WGS as a diagnostic test for genetic disorders

Whole-exome sequencing enables rapid and prenatal diagnosis of inherited skin disorders

Whole genome sequencing in clinical practice

Validation of whole genome sequencing from dried blood spots

Whole genome sequencing in the diagnosis of primary ciliary dyskinesia

Establishment and genetically characterization of patient-derived xenograft models of cervical cancer

A clinically validated whole genome pipeline for structural variant detection and analysis

Whole-genome sequencing, as a powerful diagnostic tool in hearing loss, reveals novel variants in PTPRQ missed by whole-exome sequencing

Genotyping of human neutrophil antigens (HNA) from whole genome sequencing data

Test development, optimization and validation of a WGS pipeline for genetic disorders