|
| Status |
Public on Jul 12, 2017 |
| Title |
Single-cell alternative splicing analysis with Expedition reveals splicing dynamics during neuron differentiation |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
|
| Summary |
Alternative splicing (AS) generates isoform diversity critical for cellular identity and homeostasis, yet characterization of this diversity in single cells remains limited. We developed Expedition, a computational framework to categorize and visualize the heterogeneity of AS from single-cell transcriptomes. Expedition consists of (i) outrigger, a de novo splice graph transversal algorithm to detect AS from single cell RNA-seq; (ii) anchor, a Bayesian approach to assign splicing modalities and (iii) bonvoyage, using non-negative matrix factorization to visualize modality changes. By applying Expedition to single iPSCs undergoing neuron differentiation, we discover that 25% of AS exons exhibit bimodality and are flanked by longer and more conserved introns harboring distinct cis-regulatory motifs. Bimodal exons are highly dynamic during cellular transitions, preserve translatability, enriched in recently emerged genes and have conserved AS in mammals. Applying Expedition (http://github.com/YeoLab/Expedition) in single cells redefines our estimates and understanding of AS in evolution and biology.
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| |
|
| Overall design |
Analysis of alternative splicing changes across motor neuron differentiation
|
| |
|
| Contributor(s) |
Botvinnik OB, Song Y |
| Citation(s) |
28673540 |
| Submission date |
Aug 22, 2016 |
| Last update date |
May 15, 2019 |
| Contact name |
Gene Yeo |
| E-mail(s) |
geneyeo@ucsd.edu
|
| Organization name |
UCSD
|
| Street address |
2880 Torrey Pines Scenic Dr. Room 3805/Yeo Lab
|
| City |
La Jolla |
| State/province |
CA |
| ZIP/Postal code |
92037 |
| Country |
USA |
| |
|
| Platforms (1) |
| GPL11154 |
Illumina HiSeq 2000 (Homo sapiens) |
|
| Samples (214)
|
|
| Relations |
| BioProject |
PRJNA339740 |
| SRA |
SRP082522 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE85908_alternative_exons.bed.gz |
962.1 Kb |
(ftp)(http) |
BED |
| GSE85908_cisbp_metadata.csv.gz |
6.3 Kb |
(ftp)(http) |
CSV |
| GSE85908_cisbp_t_statistic.csv.gz |
33.3 Kb |
(ftp)(http) |
CSV |
| GSE85908_constitutive_exons.bed.gz |
70.6 Kb |
(ftp)(http) |
BED |
| GSE85908_expression.csv.gz |
12.1 Mb |
(ftp)(http) |
CSV |
| GSE85908_expression_feature.csv.gz |
1.3 Mb |
(ftp)(http) |
CSV |
| GSE85908_hg19_phastcons_placental_mammal.wig.gz |
8.8 Gb |
(ftp)(http) |
WIG |
| GSE85908_kmer_zscores.csv.gz |
926.8 Kb |
(ftp)(http) |
CSV |
| GSE85908_kmer_zscores_metadata.csv.gz |
332 b |
(ftp)(http) |
CSV |
| GSE85908_mapping_stats.csv.gz |
25.2 Kb |
(ftp)(http) |
CSV |
| GSE85908_metadata.csv.gz |
919 b |
(ftp)(http) |
CSV |
| GSE85908_modalities_tidy.csv.gz |
624.8 Kb |
(ftp)(http) |
CSV |
| GSE85908_splicing.csv.gz |
1.4 Mb |
(ftp)(http) |
CSV |
| GSE85908_splicing_feature.csv.gz |
2.7 Mb |
(ftp)(http) |
CSV |
| GSE85908_voyages.csv.gz |
432.7 Kb |
(ftp)(http) |
CSV |
| GSE85908_waypoints.csv.gz |
627.6 Kb |
(ftp)(http) |
CSV |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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