Abstract:
:Integrating single-cell RNA sequencing (scRNA-seq) data with genotypes obtained from DNA sequencing studies facilitates the detection of functional genetic variants underlying cell type-specific gene expression variation. Unfortunately, most existing scRNA-seq studies do not come with DNA sequencing data; thus, being able to call single nucleotide variants (SNVs) from scRNA-seq data alone can provide crucial and complementary information, detection of functional SNVs, maximizing the potential of existing scRNA-seq studies. Here, we perform extensive analyses to evaluate the utility of two SNV calling pipelines (GATK and Monovar), originally designed for SNV calling in either bulk or single-cell DNA sequencing data. In both pipelines, we examined various parameter settings to determine the accuracy of the final SNV call set and provide practical recommendations for applied analysts. We found that combining all reads from the single cells and following GATK Best Practices resulted in the highest number of SNVs identified with a high concordance. In individual single cells, Monovar resulted in better quality SNVs even though none of the pipelines analyzed is capable of calling a reasonable number of SNVs with high accuracy. In addition, we found that SNV calling quality varies across different functional genomic regions. Our results open doors for novel ways to leverage the use of scRNA-seq for the future investigation of SNV function.
journal_name
Hum Mol Genetjournal_title
Human molecular geneticsauthors
Schnepp PM,Chen M,Keller ET,Zhou Xdoi
10.1093/hmg/ddz207subject
Has Abstractpub_date
2019-11-01 00:00:00pages
3569-3583issue
21eissn
0964-6906issn
1460-2083pii
5553547journal_volume
28pub_type
杂志文章abstract::Senataxin, encoded by the SETX gene, contributes to multiple aspects of gene expression, including transcription and RNA processing. Mutations in SETX cause the recessive disorder ataxia with oculomotor apraxia type 2 (AOA2) and a dominant juvenile form of amyotrophic lateral sclerosis (ALS4). To assess the functional...
journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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更新日期:2005-08-15 00:00:00
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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doi:10.1093/hmg/ddg122
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddm225
更新日期:2007-11-15 00:00:00
abstract::F1Fo-ATP synthase is a key enzyme of mitochondrial energy provision producing most of cellular ATP. So far, mitochondrial diseases caused by isolated disorders of the ATP synthase have been shown to result from mutations in mtDNA genes for the subunits ATP6 and ATP8 or in nuclear genes encoding the biogenesis factors ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddq254
更新日期:2010-09-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/7.13.2045
更新日期:1998-12-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddp304
更新日期:2009-10-01 00:00:00
abstract::Single-nucleotide polymorphism (SNP) tagging is widely used as a way of saving genotyping costs in association studies. A number of different tagging methods have been developed to reduce the number of markers to be genotyped while maintaining power for detecting effects on non-assayed SNPs. How the different methods ...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi309
更新日期:2005-09-15 00:00:00
abstract::Alterations in mitochondrial DNA (mtDNA) and consequent loss of mitochondrial function underlie the mitochondrial theory of aging. In this study, we systematically analyzed the mtDNA control region somatic mutation pattern in 2864 single hematopoietic stem cells (HSCs) and progenitors, isolated by flow cytometry sorti...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddl457
更新日期:2007-02-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/9.13.2009
更新日期:2000-08-12 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr512
更新日期:2012-02-15 00:00:00
abstract::Presenilins 1 and 2 (PS1/2), causative molecules for familial Alzheimer's disease (FAD), are multipass transmembrane proteins localized predominantly in the endoplasmic reticulum (ER) and Golgi apparatus. Heteromeric protein complexes containing PS1/2 are thought to participate in several functions, including intramem...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddi195
更新日期:2005-07-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddr530
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:2012-04-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddh085
更新日期:2004-04-01 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/10.21.2329
更新日期:2001-10-01 00:00:00
abstract::An increased rate of de novo copy number variants (CNVs) has been found in schizophrenia (SZ), autism and developmental delay. An increased rate has also been reported in bipolar affective disorder (BD). Here, in a larger BD sample, we aimed to replicate these findings and compare de novo CNVs between SZ and BD. We us...
journal_title:Human molecular genetics
pub_type: 杂志文章
doi:10.1093/hmg/ddu379
更新日期:2014-12-15 00:00:00
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journal_title:Human molecular genetics
pub_type: 杂志文章
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更新日期:1995-01-01 00:00:00
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pub_type: 杂志文章
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journal_title:Human molecular genetics
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更新日期:2016-06-01 00:00:00
abstract::Small, submicroscopic, genomic deletions and duplications (1 kb to 10 Mb) constitute up to 15% of all mutations underlying human monogenic diseases. Novel genomic technologies such as microarray-based comparative genomic hybridization (array CGH) allow the mapping of genomic copy number alterations at this submicrosco...
journal_title:Human molecular genetics
pub_type: 杂志文章,评审
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更新日期:2005-10-15 00:00:00