IDEAS home Printed from https://ideas.repec.org/a/plo/pone00/0008529.html
   My bibliography  Save this article

A Statistical Method for the Detection of Alternative Splicing Using RNA-Seq

Author

Listed:
  • Liguo Wang
  • Yuanxin Xi
  • Jun Yu
  • Liping Dong
  • Laising Yen
  • Wei Li

Abstract

Deep sequencing of transcriptome (RNA-seq) provides unprecedented opportunity to interrogate plausible mRNA splicing patterns by mapping RNA-seq reads to exon junctions (thereafter junction reads). In most previous studies, exon junctions were detected by using the quantitative information of junction reads. The quantitative criterion (e.g. minimum of two junction reads), although is straightforward and widely used, usually results in high false positive and false negative rates, owning to the complexity of transcriptome. Here, we introduced a new metric, namely Minimal Match on Either Side of exon junction (MMES), to measure the quality of each junction read, and subsequently implemented an empirical statistical model to detect exon junctions. When applied to a large dataset (>200M reads) consisting of mouse brain, liver and muscle mRNA sequences, and using independent transcripts databases as positive control, our method was proved to be considerably more accurate than previous ones, especially for detecting junctions originated from low-abundance transcripts. Our results were also confirmed by real time RT-PCR assay. The MMES metric can be used either in this empirical statistical model or in other more sophisticated classifiers, such as logistic regression.

Suggested Citation

  • Liguo Wang & Yuanxin Xi & Jun Yu & Liping Dong & Laising Yen & Wei Li, 2010. "A Statistical Method for the Detection of Alternative Splicing Using RNA-Seq," PLOS ONE, Public Library of Science, vol. 5(1), pages 1-8, January.
  • Handle: RePEc:plo:pone00:0008529
    DOI: 10.1371/journal.pone.0008529
    as

    Download full text from publisher

    File URL: https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0008529
    Download Restriction: no

    File URL: https://journals.plos.org/plosone/article/file?id=10.1371/journal.pone.0008529&type=printable
    Download Restriction: no

    File URL: https://libkey.io/10.1371/journal.pone.0008529?utm_source=ideas
    LibKey link: if access is restricted and if your library uses this service, LibKey will redirect you to where you can use your library subscription to access this item
    ---><---

    References listed on IDEAS

    as
    1. Eric T. Wang & Rickard Sandberg & Shujun Luo & Irina Khrebtukova & Lu Zhang & Christine Mayr & Stephen F. Kingsmore & Gary P. Schroth & Christopher B. Burge, 2008. "Alternative isoform regulation in human tissue transcriptomes," Nature, Nature, vol. 456(7221), pages 470-476, November.
    2. Christopher A. Maher & Chandan Kumar-Sinha & Xuhong Cao & Shanker Kalyana-Sundaram & Bo Han & Xiaojun Jing & Lee Sam & Terrence Barrette & Nallasivam Palanisamy & Arul M. Chinnaiyan, 2009. "Transcriptome sequencing to detect gene fusions in cancer," Nature, Nature, vol. 458(7234), pages 97-101, March.
    Full references (including those not matched with items on IDEAS)

    Most related items

    These are the items that most often cite the same works as this one and are cited by the same works as this one.
    1. Gustavo Glusman & Juan Caballero & Max Robinson & Burak Kutlu & Leroy Hood, 2013. "Optimal Scaling of Digital Transcriptomes," PLOS ONE, Public Library of Science, vol. 8(11), pages 1-12, November.
    2. Xiaohong Li & Guy N Brock & Eric C Rouchka & Nigel G F Cooper & Dongfeng Wu & Timothy E O’Toole & Ryan S Gill & Abdallah M Eteleeb & Liz O’Brien & Shesh N Rai, 2017. "A comparison of per sample global scaling and per gene normalization methods for differential expression analysis of RNA-seq data," PLOS ONE, Public Library of Science, vol. 12(5), pages 1-22, May.
    3. Jun Inamo & Akari Suzuki & Mahoko Takahashi Ueda & Kensuke Yamaguchi & Hiroshi Nishida & Katsuya Suzuki & Yuko Kaneko & Tsutomu Takeuchi & Hiroaki Hatano & Kazuyoshi Ishigaki & Yasushi Ishihama & Kazu, 2024. "Long-read sequencing for 29 immune cell subsets reveals disease-linked isoforms," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    4. Areum Han & Peter Stoilov & Anthony J Linares & Yu Zhou & Xiang-Dong Fu & Douglas L Black, 2014. "De Novo Prediction of PTBP1 Binding and Splicing Targets Reveals Unexpected Features of Its RNA Recognition and Function," PLOS Computational Biology, Public Library of Science, vol. 10(1), pages 1-18, January.
    5. Judith A Potashkin & Jose A Santiago & Bernard M Ravina & Arthur Watts & Alexey A Leontovich, 2012. "Biosignatures for Parkinson’s Disease and Atypical Parkinsonian Disorders Patients," PLOS ONE, Public Library of Science, vol. 7(8), pages 1-13, August.
    6. Wei Hu & Yangjun Wu & Qili Shi & Jingni Wu & Deping Kong & Xiaohua Wu & Xianghuo He & Teng Liu & Shengli Li, 2022. "Systematic characterization of cancer transcriptome at transcript resolution," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    7. Jianfei Hu & Eli Boritz & William Wylie & Daniel C Douek, 2017. "Stochastic principles governing alternative splicing of RNA," PLOS Computational Biology, Public Library of Science, vol. 13(9), pages 1-20, September.
    8. Hillary M. Heiling & Douglas R. Wilson & Naim U. Rashid & Wei Sun & Joseph G. Ibrahim, 2023. "Estimating cell type composition using isoform expression one gene at a time," Biometrics, The International Biometric Society, vol. 79(2), pages 854-865, June.
    9. Seungjae Lee & Yen-Chung Chen & Austin E. Gillen & J. Matthew Taliaferro & Bart Deplancke & Hongjie Li & Eric C. Lai, 2022. "Diverse cell-specific patterns of alternative polyadenylation in Drosophila," Nature Communications, Nature, vol. 13(1), pages 1-16, December.
    10. Jungsoo Gim & Sungho Won & Taesung Park, 2016. "LPEseq: Local-Pooled-Error Test for RNA Sequencing Experiments with a Small Number of Replicates," PLOS ONE, Public Library of Science, vol. 11(8), pages 1-15, August.
    11. Wei Sun & Yufeng Liu & James J. Crowley & Ting-Huei Chen & Hua Zhou & Haitao Chu & Shunping Huang & Pei-Fen Kuan & Yuan Li & Darla Miller & Ginger Shaw & Yichao Wu & Vasyl Zhabotynsky & Leonard McMill, 2015. "IsoDOT Detects Differential RNA-Isoform Expression/Usage With Respect to a Categorical or Continuous Covariate With High Sensitivity and Specificity," Journal of the American Statistical Association, Taylor & Francis Journals, vol. 110(511), pages 975-986, September.
    12. Justin Bo-Kai Hsu & Neil Arvin Bretaña & Tzong-Yi Lee & Hsien-Da Huang, 2011. "Incorporating Evolutionary Information and Functional Domains for Identifying RNA Splicing Factors in Humans," PLOS ONE, Public Library of Science, vol. 6(11), pages 1-11, November.
    13. Stacey D Wagner & Adam J Struck & Riti Gupta & Dylan R Farnsworth & Amy E Mahady & Katy Eichinger & Charles A Thornton & Eric T Wang & J Andrew Berglund, 2016. "Dose-Dependent Regulation of Alternative Splicing by MBNL Proteins Reveals Biomarkers for Myotonic Dystrophy," PLOS Genetics, Public Library of Science, vol. 12(9), pages 1-24, September.
    14. Christopher G Bell & Sarah Finer & Cecilia M Lindgren & Gareth A Wilson & Vardhman K Rakyan & Andrew E Teschendorff & Pelin Akan & Elia Stupka & Thomas A Down & Inga Prokopenko & Ian M Morison & Jonat, 2010. "Integrated Genetic and Epigenetic Analysis Identifies Haplotype-Specific Methylation in the FTO Type 2 Diabetes and Obesity Susceptibility Locus," PLOS ONE, Public Library of Science, vol. 5(11), pages 1-12, November.
    15. Huihui Liu & Hongchao Liu & Longhao Wang & Lei Song & Guixian Jiang & Qing Lu & Tao Yang & Hu Peng & Ruijie Cai & Xingle Zhao & Ting Zhao & Hao Wu, 2023. "Cochlear transcript diversity and its role in auditory functions implied by an otoferlin short isoform," Nature Communications, Nature, vol. 14(1), pages 1-19, December.
    16. Saikat Bhattacharya & Suman Wang & Divya Reddy & Siyuan Shen & Ying Zhang & Ning Zhang & Hua Li & Michael P. Washburn & Laurence Florens & Yunyu Shi & Jerry L. Workman & Fudong Li, 2021. "Structural basis of the interaction between SETD2 methyltransferase and hnRNP L paralogs for governing co-transcriptional splicing," Nature Communications, Nature, vol. 12(1), pages 1-15, December.
    17. Yaqi Su & Zhejian Yu & Siqian Jin & Zhipeng Ai & Ruihong Yuan & Xinyi Chen & Ziwei Xue & Yixin Guo & Di Chen & Hongqing Liang & Zuozhu Liu & Wanlu Liu, 2024. "Comprehensive assessment of mRNA isoform detection methods for long-read sequencing data," Nature Communications, Nature, vol. 15(1), pages 1-19, December.
    18. Vinícius Diniz Mayrink & Flávio B. Gonçalves, 2020. "Identifying atypically expressed chromosome regions using RNA-Seq data," Statistical Methods & Applications, Springer;Società Italiana di Statistica, vol. 29(3), pages 619-649, September.
    19. Zhiping Zhang & Bongmin Bae & Winston H. Cuddleston & Pedro Miura, 2023. "Coordination of alternative splicing and alternative polyadenylation revealed by targeted long read sequencing," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    20. Feng Wang & Yang Xu & Robert Wang & Beatrice Zhang & Noah Smith & Amber Notaro & Samantha Gaerlan & Eric Kutschera & Kathryn E. Kadash-Edmondson & Yi Xing & Lan Lin, 2023. "TEQUILA-seq: a versatile and low-cost method for targeted long-read RNA sequencing," Nature Communications, Nature, vol. 14(1), pages 1-15, December.

    More about this item

    Statistics

    Access and download statistics

    Corrections

    All material on this site has been provided by the respective publishers and authors. You can help correct errors and omissions. When requesting a correction, please mention this item's handle: RePEc:plo:pone00:0008529. See general information about how to correct material in RePEc.

    If you have authored this item and are not yet registered with RePEc, we encourage you to do it here. This allows to link your profile to this item. It also allows you to accept potential citations to this item that we are uncertain about.

    If CitEc recognized a bibliographic reference but did not link an item in RePEc to it, you can help with this form .

    If you know of missing items citing this one, you can help us creating those links by adding the relevant references in the same way as above, for each refering item. If you are a registered author of this item, you may also want to check the "citations" tab in your RePEc Author Service profile, as there may be some citations waiting for confirmation.

    For technical questions regarding this item, or to correct its authors, title, abstract, bibliographic or download information, contact: plosone (email available below). General contact details of provider: https://journals.plos.org/plosone/ .

    Please note that corrections may take a couple of weeks to filter through the various RePEc services.

    IDEAS is a RePEc service. RePEc uses bibliographic data supplied by the respective publishers.