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Wright, David J., Hall, Nicola A. L., Irish, Naomi, Man, Angela L., Glynn, Will, Mould, Arne, De Los Angeles, Alejandro, Angiolini, Emily, Swarbreck, David, Gharbi, Karim, Tunbridge, Elizabeth M. and Haerty, Wilfried 
ORCID: https://orcid.org/0000-0003-0111-191X
(2022)
Long read sequencing reveals novel isoforms and insights into splicing regulation during cell state changes.
BMC Genomics, 23 (1).
ISSN 1471-2164
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Abstract
Background: Alternative splicing is a key mechanism underlying cellular differentiation and a driver of complexity in mammalian neuronal tissues. However, understanding of which isoforms are differentially used or expressed and how this affects cellular differentiation remains unclear. Long read sequencing allows full-length transcript recovery and quantification, enabling transcript-level analysis of alternative splicing processes and how these change with cell state. Here, we utilise Oxford Nanopore Technologies sequencing to produce a custom annotation of a well-studied human neuroblastoma cell line SH-SY5Y, and to characterise isoform expression and usage across differentiation. Results: We identify many previously unannotated features, including a novel transcript of the voltage-gated calcium channel subunit gene, CACNA2D2. We show differential expression and usage of transcripts during differentiation identifying candidates for future research into state change regulation. Conclusions: Our work highlights the potential of long read sequencing to uncover previously unknown transcript diversity and mechanisms influencing alternative splicing.
| Item Type: | Article |
|---|---|
| Additional Information: | Funding Information: The authors acknowledge the support of the UK Medical Research Council and of the Biotechnology and Biological Sciences Research Council (BBSRC), part of UK Research and Innovation. The authors also acknowledge the support and work delivered at the Earlham Institute by members of the EI Biofoundry and the technical assistance of the Norwich Research Park CiS team. The authors would like to also thank the editor and reviewers for insightful peer review that greatly improved the manuscript. This study makes grateful use of Genotype-Tissue Expression (GTEx) Project v.8 data which is supported by the Common Fund of the Office of the Director of the National Institutes of Health, and by NCI, NHGRI, NHLBI, NIDA, NIMH, and NINDS. The views expressed are those of the authors and not necessarily those of the National Health Service, NIHR or the Department of Health. |
| Uncontrolled Keywords: | biotechnology,genetics ,/dk/atira/pure/subjectarea/asjc/1300/1305 |
| Faculty \ School: | Faculty of Science > School of Pharmacy (former - to 2024) Faculty of Science > School of Biological Sciences Faculty of Medicine and Health Sciences > Norwich Medical School Faculty of Medicine and Health Sciences > School of Health Sciences |
| UEA Research Groups: | Faculty of Medicine and Health Sciences > Research Centres > Norwich Institute for Healthy Aging Faculty of Science > Research Groups > Patient Care |
| Related URLs: | |
| Depositing User: | LivePure Connector |
| Date Deposited: | 16 Sep 2022 13:36 |
| Last Modified: | 15 Dec 2024 01:25 |
| URI: | https://ueaeprints.uea.ac.uk/id/eprint/88391 |
| DOI: | 10.1186/s12864-021-08261-2 |
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