Skip to content
2000
Volume 26, Issue 4
  • ISSN: 1389-2029
  • E-ISSN: 1875-5488

Abstract

Introduction

Ubiquitination, a unique post-translational modification, plays a cardinal role in diverse cellular functions such as protein degradation, signal transduction, DNA repair, and regulation of cell cycle. Thus, accurate prediction of potential ubiquitination sites is an urgent requirement for exploring the ubiquitination mechanism as well as the disease pathogenesis associated with ubiquitination processes.

Methods

This study introduces a novel deep learning architecture, ResUbiNet, which utilized a protein language model (ProtTrans), amino acid properties, and BLOSUM62 matrix for sequence embedding and multiple state-of-the-art architectural components, ., transformer, multi-kernel convolution, residual connection, and squeeze-and-excitation for feature extractions.

Results

The results of cross-validation and external tests showed that the ResUbiNet model achieved better prediction performances in comparison with the available hCKSAAP_UbSite, RUBI, MDCapsUbi, and MusiteDeep models.

Conclusion

ResUbiNet’s integration of advanced features and architectures significantly enhances prediction performance, aiding in understanding ubiquitination mechanisms and related diseases.

Loading

Article metrics loading...

/content/journals/cg/10.2174/0113892029331751240820111158
2024-08-27
2025-09-02
Loading full text...

Full text loading...

References

  1. SwatekK.N. KomanderD. Ubiquitin modifications.Cell Res.201626439942210.1038/cr.2016.3927012465
    [Google Scholar]
  2. GrossegesseM. DoellingerJ. FritschA. LaueM. PieskerJ. SchaadeL. NitscheA. Global ubiquitination analysis reveals extensive modification and proteasomal degradation of cowpox virus proteins, but preservation of viral cores.Sci. Rep.201881180710.1038/s41598‑018‑20130‑929379051
    [Google Scholar]
  3. ThrowerJ.S. HoffmanL. RechsteinerM. PickartC.M. Recognition of the polyubiquitin proteolytic signal.EMBO J.20001919410210.1093/emboj/19.1.9410619848
    [Google Scholar]
  4. AyeshaM.P. MarshE.N.G. The antiviral enzyme, viperin, activates protein ubiquitination by the E3 ubiquitin ligase, TRAF6J Am Chem Soc.2021143134910491410.1021/jacs.1c01045.
    [Google Scholar]
  5. YauR. RapeM. The increasing complexity of the ubiquitin code.Nat. Cell Biol.201618657958610.1038/ncb335827230526
    [Google Scholar]
  6. SunL. ChenZ.J. The novel functions of ubiquitination in signaling.Curr. Opin. Cell Biol.200416211912610.1016/j.ceb.2004.02.00515196553
    [Google Scholar]
  7. MorrisJ.R. Attenuation of the ubiquitin conjugate DNA damage signal by the proteasomal DUB POH1.Cell Cycle201211224103410410.4161/cc.2239523075493
    [Google Scholar]
  8. JacksonS.P. DurocherD. Regulation of DNA damage responses by ubiquitin and SUMO.Mol. Cell201349579580710.1016/j.molcel.2013.01.01723416108
    [Google Scholar]
  9. KaiserP. SuN-Y. The yeast ubiquitin ligase SCFMet30: Connecting environmental and intracellular conditions to cell division.Cell Division2006111610.1186/1747‑1028‑1‑16.
    [Google Scholar]
  10. PinesJ. Cubism and the cell cycle: The many faces of the APC/C.Nat. Rev. Mol. Cell Biol.201112742743810.1038/nrm313221633387
    [Google Scholar]
  11. PickartC.M. Mechanisms underlying ubiquitination.Annu. Rev. Biochem.200170150353310.1146/annurev.biochem.70.1.50311395416
    [Google Scholar]
  12. PickartC.M. EddinsM.J. Ubiquitin: structures, functions, mechanisms.Biochim Biophys Acta200416951-3557210.1016/j.bbamcr.2004.09.019.
    [Google Scholar]
  13. KomanderD. The emerging complexity of protein ubiquitination.Biochem. Soc. Trans.200937593795310.1042/BST037093719754430
    [Google Scholar]
  14. DikicI. Proteasomal and autophagic degradation systems.Annu. Rev. Biochem.201786119322410.1146/annurev‑biochem‑061516‑04490828460188
    [Google Scholar]
  15. SunT. LiuZ. YangQ. The role of ubiquitination and deubiquitination in cancer metabolism.Mol. Cancer202019114610.1186/s12943‑020‑01262‑x33004065
    [Google Scholar]
  16. TakuA. YuzuruI. Mitophagy regulated by the PINK1-parkin pathway.Cell Death - Autophagy, Apoptosis and NecrosisInTech open201510.5772/61284.
    [Google Scholar]
  17. PodvinS. RosenthalS.B. PoonW. WeiE. FischK.M. HookV. Mutant huntingtin protein interaction map implicates dysregulation of multiple cellular pathways in neurodegeneration of huntington’s disease.J. Huntingtons Dis.202211324326710.3233/JHD‑22053835871359
    [Google Scholar]
  18. RadivojacP. VacicV. HaynesC. CocklinR.R. MohanA. HeyenJ.W. GoeblM.G. IakouchevaL.M. Identification, analysis, and prediction of protein ubiquitination sites.Proteins201078236538010.1002/prot.2255519722269
    [Google Scholar]
  19. KangM. OhJ.H. Editorial of special issue “Deep learning and machine learning in bioinformatics”Int. J. Mol. Sci.20222312661010.3390/ijms23126610.
    [Google Scholar]
  20. MinS. LeeB. YoonS. Deep learning in bioinformatics.Brief. Bioinform.201718585186927473064
    [Google Scholar]
  21. RamsundarB. EastmanP. WaltersP. Deep learning for the life sciences: Applying deep learning to genomics, microscopy, drug discovery, and more.O'Reilly Media, Inc.2019Available from: https://dokumen.pub/deep-learning-for-the-life-sciences-applying-deep-learning-to-genomics-microscopy-drug-discovery-and-more-1nbsped-1492039837-978-1492039839.html
    [Google Scholar]
  22. LuoR. SedlazeckF J. LamT-W. A multi-task convolutional deep neural network for variant calling in single molecule sequencing.Nat. Commun.201910199810.1038/s41467‑019‑09025‑z.
    [Google Scholar]
  23. QuangD. XieX. DanQ: a hybrid convolutional and recurrent deep neural network for quantifying the function of DNA sequences.201510.1101/032821.
    [Google Scholar]
  24. ZhangH. HungC.L. LiuM. HuX. LinY.Y. NCNet: Deep learning network models for predicting function of non-coding DNA.Front. Genet.20191043210.3389/fgene.2019.0043231191597
    [Google Scholar]
  25. ThomasJ. SaelL. Deep neural network based precursor microRNA prediction on eleven species2017Available from: https://www.researchgate.net/publication/316078717_Deep_Neural_Network_Based_Precursor_microRNA_Prediction_on_Eleven_Species
    [Google Scholar]
  26. ThomasJ. ThomasS. SaelL. DP-miRNA: An improved prediction of precursor microRNA using deep learning model.IEEE International Conference on Big Data and Smart Computing (BigComp)201710.1109/BIGCOMP.2017.7881722.
    [Google Scholar]
  27. ZhengX. FuX. WangK. WangM. Deep neural networks for human microRNA precursor detection.BMC Bioinformatics20202111710.1186/s12859‑020‑3339‑731931701
    [Google Scholar]
  28. VaradiM. AnyangoS. DeshpandeM. NairS. NatassiaC. YordanovaG. YuanD. StroeO. WoodG. LaydonA. ŽídekA. GreenT. TunyasuvunakoolK. PetersenS. JumperJ. ClancyE. GreenR. VoraA. LutfiM. FigurnovM. CowieA. HobbsN. KohliP. KleywegtG. BirneyE. HassabisD. VelankarS. AlphaFold Protein Structure Database: Massively expanding the structural coverage of protein-sequence space with high-accuracy models.Nucleic Acids Res.202250D1D439D44410.1093/nar/gkab106134791371
    [Google Scholar]
  29. TorrisiM. PollastriG. LeQ. Deep learning methods in protein structure prediction.Comput. Struct. Biotechnol. J.2020181301131010.1016/j.csbj.2019.12.01132612753
    [Google Scholar]
  30. ChenZ. LiuX. LiF. LiC. Marquez-LagoT. LeierA. AkutsuT. WebbG.I. XuD. SmithA.I. LiL. ChouK.C. SongJ. Large-scale comparative assessment of computational predictors for lysine post-translational modification sites.Brief. Bioinform.20192062267229010.1093/bib/bby08930285084
    [Google Scholar]
  31. TungC.W. HoS.Y. Computational identification of ubiquitylation sites from protein sequences.BMC Bioinformatics20089131010.1186/1471‑2105‑9‑31018625080
    [Google Scholar]
  32. ChenZ. ChenY.Z. WangX.F. WangC. YanR.X. ZhangZ. Prediction of ubiquitination sites by using the composition of k-spaced amino acid pairs.PLoS One201167e2293010.1371/journal.pone.002293021829559
    [Google Scholar]
  33. ChenZ. ZhouY. SongJ. ZhangZ. hCKSAAP_UbSite: Improved prediction of human ubiquitination sites by exploiting amino acid pattern and properties.Biochim. Biophys. Acta. Proteins Proteomics2013183481461146710.1016/j.bbapap.2013.04.00623603789
    [Google Scholar]
  34. WalshI. Di DomenicoT. TosattoS.C.E. RUBI: rapid proteomic-scale prediction of lysine ubiquitination and factors influencing predictor performance.Amino Acids201446485386210.1007/s00726‑013‑1645‑324363213
    [Google Scholar]
  35. WalshI. MartinA.J.M. Di DomenicoT. TosattoS.C.E. ESpritz: accurate and fast prediction of protein disorder.Bioinformatics201228450350910.1093/bioinformatics/btr68222190692
    [Google Scholar]
  36. WangX. YanR. WangY. Computational identification of human ubiquitination sites using convolutional and recurrent neural networks.Mol. Omics202117694895510.1039/D0MO00183J34515266
    [Google Scholar]
  37. LiW. WangJ. LuoY. BezabihT.T. Multi-dimensional feature recognition model based on capsule network for ubiquitination site prediction.PeerJ202210e1442710.7717/peerj.1442736523471
    [Google Scholar]
  38. WangD. LiuD. YuchiJ. HeF. JiangY. CaiS. LiJ. XuD. MusiteDeep: a deep-learning based webserver for protein post-translational modification site prediction and visualization.Nucleic Acids Res.202048W1W140W14610.1093/nar/gkaa27532324217
    [Google Scholar]
  39. ElnaggarA. HeinzingerM. DallagoC. RehawiG. WangY. JonesL. GibbsT. FeherT. AngererC. SteineggerM. BhowmikD. RostB. Prottrans: Toward understanding the language of life through self-supervised learning.IEEE Trans. Pattern Anal. Mach. Intell.202244107112712710.1109/TPAMI.2021.309538134232869
    [Google Scholar]
  40. RaffelC. ShazeerN. RobertsA. Exploring the limits of transfer learning with a unified text-to-text transformer.J. Mach. Learn. Res.202021140167Available from: https://jmlr.org/papers/v21/20-074.html
    [Google Scholar]
  41. KawashimaS. PokarowskiP. PokarowskaM. KolinskiA. KatayamaT. KanehisaM. AAindex: Amino acid index database, progress report 2008.Nucleic Acids Res.200836D202D20517998252
    [Google Scholar]
  42. EddyS.R. Where did the BLOSUM62 alignment score matrix come from?Nat. Biotechnol.20042281035103610.1038/nbt0804‑103515286655
    [Google Scholar]
  43. VaswaniA. ShazeerN. ParmarN. Attention is all you need.20173010.48550/arXiv.1706.03762.
    [Google Scholar]
  44. BrownT. MannB. RyderN. Language models are few-shot learners.2020Available from: https://www.researchgate.net/publication/341724146_Language_Models_are_Few-Shot_Learners
    [Google Scholar]
  45. DevlinJ. ChangM-W. LeeK. Bert: Pre-training of deep bidirectional transformers for language understanding2018Available from: https://www.researchgate.net/publication/328230984_BERT_Pre-training_of_Deep_Bidirectional_Transformers_for_Language_Understanding
    [Google Scholar]
  46. RadfordA. NarasimhanK. SalimansT. Improving language understanding by generative pre-training.2018Available from: https://www.bibsonomy.org/bibtex/273ced32c0d4588eb95b6986dc2c8147c/jonaskaiser
    [Google Scholar]
  47. HuJ. ShenL. SunG. Squeeze-and-excitation networksIEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR)201810.1109/CVPR.2018.00745
    [Google Scholar]
  48. VacicV. IakouchevaL.M. RadivojacP. Two Sample Logo: A graphical representation of the differences between two sets of sequence alignments.Bioinformatics200622121536153710.1093/bioinformatics/btl15116632492
    [Google Scholar]
  49. MeiH. LiaoZ.H. ZhouY. LiS.Z. A new set of amino acid descriptors and its application in peptide QSARs.Biopolymers200580677578610.1002/bip.2029615895431
    [Google Scholar]
  50. CortesC. VapnikV. Support-vector networks.Mach. Learn.199520327329710.1007/BF00994018
    [Google Scholar]
  51. BreimanL. Random forests.Mach. Learn.200145153210.1023/A:1010933404324
    [Google Scholar]
  52. CoverT. HartP. Nearest neighbor pattern classification.IEEE Trans. Inf. Theory1967131212710.1109/TIT.1967.1053964
    [Google Scholar]
  53. ChenT. GuestrinC. Xgboost: A scalable tree boosting systemThe 22nd ACM SIGKDD International Conference201610.1145/2939672.2939785
    [Google Scholar]
  54. LecunY. BengioY. HintonG. Deep LearningNature201552175534364410.1038/nature14539.
    [Google Scholar]
  55. LecunY. BottouL. BengioY. HaffnerP. Gradient-based learning applied to document recognition.Proc. IEEE199886112278232410.1109/5.726791
    [Google Scholar]
  56. HochreiterS. SchmidhuberJ. Long short-term memory.Neural Comput.1997981735178010.1162/neco.1997.9.8.17359377276
    [Google Scholar]
  57. WangX. YanR. ChenY.Z. WangY. Computational identification of ubiquitination sites in Arabidopsis thaliana using convolutional neural networks.Plant Mol. Biol.2021105660161010.1007/s11103‑020‑01112‑w33527202
    [Google Scholar]
  58. WangH. WangZ. LiZ. LeeT.Y. Incorporating deep learning with word embedding to identify plant ubiquitylation sites.Front. Cell Dev. Biol.2020857219510.3389/fcell.2020.57219533102477
    [Google Scholar]
  59. HuangK.Y. LeeT.Y. KaoH.J. MaC.T. LeeC.C. LinT.H. ChangW.C. HuangH.D. dbPTM in 2019: Exploring disease association and cross-talk of post-translational modifications.Nucleic Acids Res.201947D1D298D30810.1093/nar/gky107430418626
    [Google Scholar]
  60. UniProt: A worldwide hub of protein knowledge.Nucleic Acids Res.201947D1D506D51510.1093/nar/gky104930395287
    [Google Scholar]
/content/journals/cg/10.2174/0113892029331751240820111158
Loading
/content/journals/cg/10.2174/0113892029331751240820111158
Loading

Data & Media loading...

Supplements

Supplementary material is available on the publisher’s website along with the published article.


  • Article Type:
    Research Article
Keyword(s): deep learning; prediction; ProtTrans; ResUbiNet; transformer; Ubiquitination site
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test