TY - JOUR
T1 - ASCOT identifies key regulators of neuronal subtype-specific splicing
AU - Ling, Jonathan P.
AU - Wilks, Christopher
AU - Charles, Rone
AU - Leavey, Patrick J.
AU - Ghosh, Devlina
AU - Jiang, Lizhi
AU - Santiago, Clayton P.
AU - Pang, Bo
AU - Venkataraman, Anand
AU - Clark, Brian S.
AU - Nellore, Abhinav
AU - Langmead, Ben
AU - Blackshaw, Seth
N1 - Funding Information:
We thank X. Zhang and the Johns Hopkins Ross Flow Cytometry Core Facility. We also thank the Johns Hopkins Deep Sequencing & Microarray Core Facility for sequencing services. This work was supported by grants from the NIH (R01EY020560 to SB, K99EY027844 to BSC, R01GM118568 to BL, and R01GM121459), a postdoctoral fellowship from the Johns Hopkins Kavli Neuroscience Discovery Institute to J.P.L., and seed funding from The Institute for Data Intensive Engineering and Science (IDIES) at Johns Hopkins University to B.L.
Publisher Copyright:
© 2020, The Author(s).
PY - 2020/12/1
Y1 - 2020/12/1
N2 - Public archives of next-generation sequencing data are growing exponentially, but the difficulty of marshaling this data has led to its underutilization by scientists. Here, we present ASCOT, a resource that uses annotation-free methods to rapidly analyze and visualize splice variants across tens of thousands of bulk and single-cell data sets in the public archive. To demonstrate the utility of ASCOT, we identify novel cell type-specific alternative exons across the nervous system and leverage ENCODE and GTEx data sets to study the unique splicing of photoreceptors. We find that PTBP1 knockdown and MSI1 and PCBP2 overexpression are sufficient to activate many photoreceptor-specific exons in HepG2 liver cancer cells. This work demonstrates how large-scale analysis of public RNA-Seq data sets can yield key insights into cell type-specific control of RNA splicing and underscores the importance of considering both annotated and unannotated splicing events.
AB - Public archives of next-generation sequencing data are growing exponentially, but the difficulty of marshaling this data has led to its underutilization by scientists. Here, we present ASCOT, a resource that uses annotation-free methods to rapidly analyze and visualize splice variants across tens of thousands of bulk and single-cell data sets in the public archive. To demonstrate the utility of ASCOT, we identify novel cell type-specific alternative exons across the nervous system and leverage ENCODE and GTEx data sets to study the unique splicing of photoreceptors. We find that PTBP1 knockdown and MSI1 and PCBP2 overexpression are sufficient to activate many photoreceptor-specific exons in HepG2 liver cancer cells. This work demonstrates how large-scale analysis of public RNA-Seq data sets can yield key insights into cell type-specific control of RNA splicing and underscores the importance of considering both annotated and unannotated splicing events.
UR - http://www.scopus.com/inward/record.url?scp=85077675295&partnerID=8YFLogxK
U2 - 10.1038/s41467-019-14020-5
DO - 10.1038/s41467-019-14020-5
M3 - Article
C2 - 31919425
AN - SCOPUS:85077675295
SN - 2041-1723
VL - 11
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 137
ER -