Abstract:
BACKGROUND:Early single-cell RNA-seq (scRNA-seq) studies suggested that it was unusual to see more than one isoform being produced from a gene in a single cell, even when multiple isoforms were detected in matched bulk RNA-seq samples. However, these studies generally did not consider the impact of dropouts or isoform quantification errors, potentially confounding the results of these analyses. RESULTS:In this study, we take a simulation based approach in which we explicitly account for dropouts and isoform quantification errors. We use our simulations to ask to what extent it is possible to study alternative splicing using scRNA-seq. Additionally, we ask what limitations must be overcome to make splicing analysis feasible. We find that the high rate of dropouts associated with scRNA-seq is a major obstacle to studying alternative splicing. In mice and other well-established model organisms, the relatively low rate of isoform quantification errors poses a lesser obstacle to splicing analysis. We find that different models of isoform choice meaningfully change our simulation results. CONCLUSIONS:To accurately study alternative splicing with single-cell RNA-seq, a better understanding of isoform choice and the errors associated with scRNA-seq is required. An increase in the capture efficiency of scRNA-seq would also be beneficial. Until some or all of the above are achieved, we do not recommend attempting to resolve isoforms in individual cells using scRNA-seq.
journal_name
Genome Bioljournal_title
Genome biologyauthors
Westoby J,Artemov P,Hemberg M,Ferguson-Smith Adoi
10.1186/s13059-020-01981-wsubject
Has Abstractpub_date
2020-03-23 00:00:00pages
74issue
1eissn
1474-7596issn
1474-760Xpii
10.1186/s13059-020-01981-wjournal_volume
21pub_type
杂志文章相关文献
GENOME BIOLOGY文献大全abstract::Studies of human genetic disorders have traditionally followed a reductionist paradigm. Traits are defined as Mendelian or complex based on family pedigree and population data, whereas alleles are deemed rare, common, benign, or deleterious based on their population frequencies. The availability of exome and genome da...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-016-1107-9
更新日期:2016-11-17 00:00:00
abstract::Pooled CRISPR screens allow researchers to interrogate genetic causes of complex phenotypes at the genome-wide scale and promise higher specificity and sensitivity compared to competing technologies. Unfortunately, two problems exist, particularly for CRISPRi/a screens: variability in guide efficiency and large rare o...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-018-1538-6
更新日期:2018-10-08 00:00:00
abstract::Following publication of the original article [1], the authors reported the following errors. ...
journal_title:Genome biology
pub_type: 杂志文章,已发布勘误
doi:10.1186/s13059-019-1668-5
更新日期:2019-03-11 00:00:00
abstract:BACKGROUND:Alternate splicing of key signaling molecules in the Toll-like receptor (Tlr) cascade has been shown to dramatically alter the signaling capacity of inflammatory cells, but it is not known how common this mechanism is. We provide transcriptional evidence of widespread alternate splicing in the Toll-like rece...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2006-7-2-r10
更新日期:2006-01-01 00:00:00
abstract:BACKGROUND:Xanthomonas campestris pathovar campestris (Xcc) is the causal agent of black rot disease of crucifers worldwide. The molecular genetic diversity and host specificity of Xcc are poorly understood. RESULTS:We constructed a microarray based on the complete genome sequence of Xcc strain 8004 and investigated t...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2007-8-10-r218
更新日期:2007-01-01 00:00:00
abstract::The explosive growth in taxonomic metagenome profiling methods over the past years has created a need for systematic comparisons using relevant performance criteria. The Open-community Profiling Assessment tooL (OPAL) implements commonly used performance metrics, including those of the first challenge of the initiativ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-019-1646-y
更新日期:2019-03-04 00:00:00
abstract:BACKGROUND:Next-generation sequencing (NGS) is a powerful tool for understanding both patterns of descent over time and space (phylogeography) and the molecular processes underpinning genome divergence in pathogenic bacteria. Here, we describe a synthesis between these perspectives by employing a recently developed Bay...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2012-13-12-r126
更新日期:2012-12-27 00:00:00
abstract::A report of the second annual Beyond the Genome conference held on the 19-22 September 2011 at The Universities at Shady Grove, Rockville, Maryland, USA, where increases in computing that may help make personal genomics a reality were a major focus. ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2011-12-10-308
更新日期:2011-10-24 00:00:00
abstract::Interpretation of the clinical significance of genomic alterations remains the most severe bottleneck preventing the realization of personalized medicine in cancer. We propose a knowledge commons to facilitate collaborative contributions and open discussion of clinical decision-making based on genomic events in cancer...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-014-0438-7
更新日期:2014-08-27 00:00:00
abstract::Most microbes cannot be easily cultured, and metagenomics provides a means to study them. Current techniques aim to resolve individual genomes from metagenomes, so-called metagenome-assembled genomes (MAGs). Leading approaches depend upon time series or transect studies, the efficacy of which is a function of communit...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-019-1643-1
更新日期:2019-02-26 00:00:00
abstract:BACKGROUND:Drug resistance remains a major public health challenge for malaria treatment and eradication. Individual loci associated with drug resistance to many antimalarials have been identified, but their epistasis with other resistance mechanisms has not yet been elucidated. RESULTS:We previously described two mut...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/PREACCEPT-1067113631444973
更新日期:2014-01-01 00:00:00
abstract:BACKGROUND:ADAR proteins are among the most extensively studied RNA binding proteins. They bind to their target and deaminate specific adenosines to inosines. ADAR activity is essential, and the editing of a subset of their targets is critical for viability. Recently, a huge number of novel ADAR targets were detected b...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2014-15-1-r5
更新日期:2014-01-07 00:00:00
abstract::Purification of proteins cross-linked to mRNAs has identified 800 mRNA-binding proteins and their characteristics. ...
journal_title:Genome biology
pub_type:
doi:10.1186/gb4030
更新日期:2012-07-17 00:00:00
abstract:BACKGROUND:Obesity is a particularly complex disease that at least partially involves genetic and environmental perturbations to gene-networks connecting the hypothalamus and several metabolic tissues, resulting in an energy imbalance at the systems level. RESULTS:To provide an inter-tissue view of obesity with respec...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2009-10-5-r55
更新日期:2009-01-01 00:00:00
abstract::A genomic analysis of heterogeneous colorectal tumor samples has uncovered interactions between immunophenotype and various aspects of tumor biology, with implications for informing the choice of immunotherapies for specific patients and guiding the design of personalized neoantigen-based vaccines. ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-015-0631-3
更新日期:2015-03-31 00:00:00
abstract:BACKGROUND:The relationships between proteins are often asymmetric: one protein (A) depends for its function on another protein (B), but the second protein does not depend on the first. In metabolic networks there are multiple pathways that converge into one central pathway. The enzymes in the converging pathways depen...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2009-10-2-r19
更新日期:2009-02-12 00:00:00
abstract:BACKGROUND:Human pluripotent stem cells (hPSCs) provide powerful models for studying cellular differentiations and unlimited sources of cells for regenerative medicine. However, a comprehensive single-cell level differentiation roadmap for hPSCs has not been achieved. RESULTS:We use high throughput single-cell RNA-seq...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-018-1426-0
更新日期:2018-04-05 00:00:00
abstract::MAP1-family proteins are classical microtubule-associated proteins (MAPs) that bind along the microtubule lattice. The founding members, MAP1A and MAP1B, are predominantly expressed in neurons, where they are thought to be important in the formation and development of axons and dendrites. Mammalian genomes usually con...
journal_title:Genome biology
pub_type: 杂志文章,评审
doi:10.1186/gb-2006-7-6-224
更新日期:2006-01-01 00:00:00
abstract::As DNA sequencing outpaces improvements in computer speed, there is a critical need to accelerate tasks like alignment and SNP calling. Crossbow is a cloud-computing software tool that combines the aligner Bowtie and the SNP caller SOAPsnp. Executing in parallel using Hadoop, Crossbow analyzes data comprising 38-fold ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2009-10-11-r134
更新日期:2009-01-01 00:00:00
abstract::Genetic studies have identified more than 150 autoimmune loci, and next-generation sequencing will identify more. Is it time to make human the model organism for autoimmune research? ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2010-11-5-212
更新日期:2010-01-01 00:00:00
abstract::In most eukaryotes, histones, which are the major structural components of chromatin, are expressed as a family of sequence variants encoded by multiple genes. Because different histone variants can contribute to a distinct or unique nucleosomal architecture, this heterogeneity can be exploited to regulate a wide rang...
journal_title:Genome biology
pub_type: 杂志文章,评审
doi:10.1186/gb-2001-2-7-reviews0006
更新日期:2001-01-01 00:00:00
abstract:BACKGROUND:Millions of humans and animals suffer from superficial infections caused by a group of highly specialized filamentous fungi, the dermatophytes, which exclusively infect keratinized host structures. To provide broad insights into the molecular basis of the pathogenicity-associated traits, we report the first ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2011-12-1-r7
更新日期:2011-01-01 00:00:00
abstract::We describe domain pair exclusion analysis (DPEA), a method for inferring domain interactions from databases of interacting proteins. DPEA features a log odds score, Eij, reflecting confidence that domains i and j interact. We analyzed 177,233 potential domain interactions underlying 26,032 protein interactions. In to...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2005-6-10-r89
更新日期:2005-01-01 00:00:00
abstract:BACKGROUND:While the song of all songbirds is controlled by the same neural circuit, the hormone dependence of singing behavior varies greatly between species. For this reason, songbirds are ideal organisms to study ultimate and proximate mechanisms of hormone-dependent behavior and neuronal plasticity. RESULTS:We pre...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-014-0578-9
更新日期:2015-01-29 00:00:00
abstract:BACKGROUND:Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes tra...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2009-10-10-r113
更新日期:2009-01-01 00:00:00
abstract:BACKGROUND:Structural variations (SVs) or copy number variations (CNVs) greatly impact the functions of the genes encoded in the genome and are responsible for diverse human diseases. Although a number of existing SV detection algorithms can detect many types of SVs using whole genome sequencing (WGS) data, no single a...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-019-1720-5
更新日期:2019-06-03 00:00:00
abstract:BACKGROUND:Pluripotency of embryonic stem (ES) cells is controlled in part by chromatin-modifying factors that regulate histone H3 lysine 4 (H3K4) methylation. However, it remains unclear how H3K4 demethylation contributes to ES cell function. RESULTS:Here, we show that KDM5B, which demethylates lysine 4 of histone H3...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2014-15-2-r32
更新日期:2014-02-04 00:00:00
abstract::Droplet-based microfluidic devices have become widely used to perform single-cell RNA sequencing (scRNA-seq). However, ambient RNA present in the cell suspension can be aberrantly counted along with a cell's native mRNA and result in cross-contamination of transcripts between different cell populations. DecontX is a n...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-020-1950-6
更新日期:2020-03-05 00:00:00
abstract:BACKGROUND:Genome editing of malaria parasites is key to the generation of live attenuated parasites used in experimental vaccination approaches. DNA repair in Plasmodium generally occurs only through homologous recombination. This has been used to generate transgenic parasites that lack one to three genes, leading to ...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/s13059-015-0811-1
更新日期:2015-11-17 00:00:00
abstract:BACKGROUND:Transcription factors (TFs) play a central role in regulating gene expression by interacting with cis-regulatory DNA elements associated with their target genes. Recent surveys have examined the DNA binding specificities of most Saccharomyces cerevisiae TFs, but a comprehensive evaluation of their data has b...
journal_title:Genome biology
pub_type: 杂志文章
doi:10.1186/gb-2011-12-12-r125
更新日期:2011-12-21 00:00:00