Discovery of Novel Protein-Coding and Long Non-coding Transcripts in Distinct Regions of the Human Brain

被引:0
作者
Santucci, Kristina [1 ]
Cheng, Yuning [1 ]
Xu, Si-Mei [1 ]
Gao, Yulan [1 ]
Lindner, Grace [1 ]
Takenaka, Konii [1 ]
Janitz, Michael [1 ]
机构
[1] Univ New South Wales, Sch Biotechnol & Biomol Sci, Sydney, Australia
关键词
Alternative splicing; Long-read sequencing; Transcript isoforms; Novel isoforms; Brain; Transcriptomics;
D O I
10.1007/s12031-025-02316-9
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Recent improvements in the accuracy of long-read sequencing (LRS) technologies have expanded the scope for novel transcriptional isoform discovery. Additionally, these advancements have improved the precision of transcript quantification, enabling a more accurate reconstruction of complex splicing patterns and transcriptomes. Thus, this project aims to take advantage of these analytical developments for the discovery and analysis of RNA isoforms in the human brain. A set of novel transcript isoforms was compiled using three bioinformatic tools, quantifying their expression across eight replicates of the cerebellar hemisphere, five replicates of the frontal cortex, and six replicates of the putamen. By taking a subset of the novel isoforms consistent across all discovery methods, a set of 170 highly confident novel RNA isoforms was curated for downstream analysis. This set consisted of 104 messenger RNAs (mRNAs) and 66 long non-coding RNAs (lncRNAs) isoforms. The detailed structure, expression, and potential encoded proteins of novel mRNA isoform BambuTx321 have been further described as an exemplary representative. Additionally, the tissue-specific expression [mean counts per million (CPM) of 5.979] of novel lncRNA, BambuTx1299, in the cerebellar hemisphere was observed. Overall, this project has identified and annotated several novel RNA isoforms across diverse tissues of the human brain, providing insights into their expression patterns and investigating their potential functional roles. Thus, this project has contributed to a more comprehensive understanding of the brain's transcriptomic landscape for applications in basic research.
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相关论文
共 67 条
[1]   Accurate structure prediction of biomolecular interactions with AlphaFold 3 [J].
Abramson, Josh ;
Adler, Jonas ;
Dunger, Jack ;
Evans, Richard ;
Green, Tim ;
Pritzel, Alexander ;
Ronneberger, Olaf ;
Willmore, Lindsay ;
Ballard, Andrew J. ;
Bambrick, Joshua ;
Bodenstein, Sebastian W. ;
Evans, David A. ;
Hung, Chia-Chun ;
O'Neill, Michael ;
Reiman, David ;
Tunyasuvunakool, Kathryn ;
Wu, Zachary ;
Zemgulyte, Akvile ;
Arvaniti, Eirini ;
Beattie, Charles ;
Bertolli, Ottavia ;
Bridgland, Alex ;
Cherepanov, Alexey ;
Congreve, Miles ;
Cowen-Rivers, Alexander I. ;
Cowie, Andrew ;
Figurnov, Michael ;
Fuchs, Fabian B. ;
Gladman, Hannah ;
Jain, Rishub ;
Khan, Yousuf A. ;
Low, Caroline M. R. ;
Perlin, Kuba ;
Potapenko, Anna ;
Savy, Pascal ;
Singh, Sukhdeep ;
Stecula, Adrian ;
Thillaisundaram, Ashok ;
Tong, Catherine ;
Yakneen, Sergei ;
Zhong, Ellen D. ;
Zielinski, Michal ;
Zidek, Augustin ;
Bapst, Victor ;
Kohli, Pushmeet ;
Jaderberg, Max ;
Hassabis, Demis ;
Jumper, John M. .
NATURE, 2024, 630 (8016) :493-500
[2]   The GTEx Consortium atlas of genetic regulatory effects across human tissues [J].
Aguet, Francois ;
Barbeira, Alvaro N. ;
Bonazzola, Rodrigo ;
Brown, Andrew ;
Castel, Stephane E. ;
Jo, Brian ;
Kasela, Silva ;
Kim-Hellmuth, Sarah ;
Liang, Yanyu ;
Parsana, Princy ;
Flynn, Elise ;
Fresard, Laure ;
Gamazon, Eric R. ;
Hamel, Andrew R. ;
He, Yuan ;
Hormozdiari, Farhad ;
Mohammadi, Pejman ;
Munoz-Aguirre, Manuel ;
Ardlie, Kristin G. ;
Battle, Alexis ;
Bonazzola, Rodrigo ;
Brown, Christopher D. ;
Cox, Nancy ;
Dermitzakis, Emmanouil T. ;
Engelhardt, Barbara E. ;
Garrido-Martin, Diego ;
Gay, Nicole R. ;
Getz, Gad ;
Guigo, Roderic ;
Hamel, Andrew R. ;
Handsaker, Robert E. ;
He, Yuan ;
Hoffman, Paul J. ;
Hormozdiari, Farhad ;
Im, Hae Kyung ;
Jo, Brian ;
Kasela, Silva ;
Kashin, Seva ;
Kim-Hellmuth, Sarah ;
Kwong, Alan ;
Lappalainen, Tuuli ;
Li, Xiao ;
Liang, Yanyu ;
MacArthur, Daniel G. ;
Mohammadi, Pejman ;
Montgomery, Stephen B. ;
Munoz-Aguirre, Manuel ;
Rouhana, John M. ;
Hormozdiari, Farhad ;
Im, Hae Kyung .
SCIENCE, 2020, 369 (6509) :1318-1330
[3]   Bayesian nonparametric discovery of isoforms and individual specific quantification [J].
Aguiar, Derek ;
Cheng, Li-Fang ;
Dumitrascu, Bianca ;
Mordelet, Fantine ;
Pai, Athma A. ;
Engelhardt, Barbara E. .
NATURE COMMUNICATIONS, 2018, 9
[4]  
ALTSCHUL SF, 1990, J MOL BIOL, V215, P403, DOI 10.1006/jmbi.1990.9999
[5]   GeneCaRNA: A Comprehensive Gene-centric Database of Human Non-coding RNAs in the GeneCards Suite [J].
Barshir, Ruth ;
Fishilevich, Simon ;
Iny-Stein, Tsippi ;
Zelig, Ofer ;
Mazor, Yaron ;
Guan-Golan, Yaron ;
Safran, Marilyn ;
Lancet, Doron .
JOURNAL OF MOLECULAR BIOLOGY, 2021, 433 (11)
[6]   rnaSPAdes: a de novo transcriptome assembler and its application to RNA-Seq data [J].
Bushmanova, Elena ;
Antipov, Dmitry ;
Lapidus, Alla ;
Prjibelski, Andrey D. .
GIGASCIENCE, 2019, 8 (09)
[7]  
Carbonell-Sala S, 2023, bioRxiv, DOI [10.1101/2023.06.16.543444, 10.1101/2023.06.16.543444, DOI 10.1101/2023.06.16.543444]
[8]   A Novel Approach to High-Quality Postmortem Tissue Procurement: The GTEx Project [J].
Carithers, Latarsha J. ;
Ardlie, Kristin ;
Barcus, Mary ;
Branton, Philip A. ;
Britton, Angela ;
Buia, Stephen A. ;
Compton, Carolyn C. ;
DeLuca, David S. ;
Peter-Demchok, Joanne ;
Gelfand, Ellen T. ;
Guan, Ping ;
Korzeniewski, Greg E. ;
Lockhart, Nicole C. ;
Rabiner, Chana A. ;
Rao, Abhi K. ;
Robinson, Karna L. ;
Roche, Nancy V. ;
Sawyer, Sherilyn J. ;
Segre, Ayellet V. ;
Shive, Charles E. ;
Smith, Anna M. ;
Sobin, Leslie H. ;
Undale, Anita H. ;
Valentino, Kimberly M. ;
Vaught, Jim ;
Young, Taylor R. ;
Moore, Helen M. .
BIOPRESERVATION AND BIOBANKING, 2015, 13 (05) :311-319
[9]   Context-aware transcript quantification from long-read RNA-seq data with Bambu [J].
Chen, Ying ;
Sim, Andre ;
Wan, Yuk Kei ;
Yeo, Keith ;
Lee, Joseph Jing Xian ;
Ling, Min Hao ;
Love, Michael I. ;
Goke, Jonathan .
NATURE METHODS, 2023, 20 (08) :1187-+
[10]   Complete characterization of the human immune cell transcriptome using accurate full-length cDNA sequencing [J].
Cole, Charles ;
Byrne, Ashley ;
Adams, Matthew ;
Volden, Roger ;
Vollmers, Christopher .
GENOME RESEARCH, 2020, 30 (04) :589-601