2014
DOI: 10.3389/fgene.2014.00016
|View full text |Cite
|
Sign up to set email alerts
|

The struggle to find reliable results in exome sequencing data: filtering out Mendelian errors

Abstract: Next Generation Sequencing studies generate a large quantity of genetic data in a relatively cost and time efficient manner and provide an unprecedented opportunity to identify candidate causative variants that lead to disease phenotypes. A challenge to these studies is the generation of sequencing artifacts by current technologies. To identify and characterize the properties that distinguish false positive variants from true variants, we sequenced a child and both parents (one trio) using DNA isolated from th… Show more

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...
2

Citation Types

4
52
0

Year Published

2015
2015
2022
2022

Publication Types

Select...
5
2
1

Relationship

1
7

Authors

Journals

citations
Cited by 51 publications
(56 citation statements)
references
References 54 publications
4
52
0
Order By: Relevance
“…Quality control and data filtering were performed on VCF files in Golden Helix's SNP and Variation Suite. Non-synonymous coding variants were compared to three control databases, including NHLBI's ESP6500 exome data (20), the 1000 genomes project (21), and an internal CCHMC control cohort (22). The initial bioinformatics analysis identified 126,752 variants (Table 3).…”
Section: Homozygous Recessive Mutation In Copb2 Identified In Two Patmentioning
confidence: 99%
See 1 more Smart Citation
“…Quality control and data filtering were performed on VCF files in Golden Helix's SNP and Variation Suite. Non-synonymous coding variants were compared to three control databases, including NHLBI's ESP6500 exome data (20), the 1000 genomes project (21), and an internal CCHMC control cohort (22). The initial bioinformatics analysis identified 126,752 variants (Table 3).…”
Section: Homozygous Recessive Mutation In Copb2 Identified In Two Patmentioning
confidence: 99%
“…The initial bioinformatics analysis identified 126,752 variants (Table 3). After filtering for quality control using filters previously described (22), coding variants, non-synonymous variants, and minor allele frequencies, we identified one single mutation which followed a homozygous recessive inheritance pattern. The identified variant was compared to known disease genes in the OMIM and Human Gene Mutation (HGMD) (23) databases, and to reported variants in dbSNP (24) and the Exome Aggregation Consortium (ExAC; (25).…”
Section: Homozygous Recessive Mutation In Copb2 Identified In Two Patmentioning
confidence: 99%
“…A significant limitation of this approach is that some of the variants called by just one method may be correct and may provide valuable insights on how to improve variant calling, but these variants are excluded from further consideration by this approach. A third approach is to sequence parent-parent-child trios and test for Mendelian consistency (Boland et al 2013;Patel et al 2014). Although this approach can detect a subset of errors, it falls short of identifying genotyping errors that do not violate inheritance in a trio (Supplemental Tables S3, S4).…”
mentioning
confidence: 99%
“…The third group of papers Cronin et al, 2014;Namjou et al, 2014;Patel et al, 2014;Sun et al, 2014) in this special issue focused on more complex analyses of the genome including copy number variants (CNV), pleiotropy combined with phenome-wide association studies (PheWAS), and epistasis (gene-gene interactions). The first paper by Namjou et al (2014) describes the first PheWAS in a pediatric cohort based on 4268 samples and 2476 sSNPs selected from previously published GWAS studies.…”
mentioning
confidence: 99%
“…Finally, how CNVs might be evaluated and used with medical records is discussed. The fifth paper of this group is by Patel et al (2014) and describes quality control processes for whole exome sequencing data, specifically using Mendelian errors as a filtering strategy to minimize errors. The group developed the Cincinnati Analytical Suite for Sequencing Informatics (CASSI) to store sequencing files, metadata, and others.…”
mentioning
confidence: 99%