Amino acid encoding methods for protein sequences: a comprehensive review and assessment
Abstract
As the first step of machine-learning based protein structure and function prediction, the amino acid encoding play a fundamental role in the final success of those methods. Different from the protein sequence encoding, the amino acid encoding can be used in both residue-level and sequence-level prediction of protein properties by combining them with different algorithms. However, it has not attracted enough attention in the past decades, and there are no comprehensive reviews and assessments about encoding methods so far. In this article, we make a systematic classification and propose a comprehensive review and assessment for various amino acid encoding methods. Those methods are grouped into five categories according to their information sources and information extraction methodologies, including binary encoding, physicochemical properties encoding, evolution-based encoding, structure-based encoding, and machine-learning encoding. Then, 16 representative methods from five categories are selected and compared on protein secondary structure prediction and protein fold recognition tasks by using large-scale benchmark datasets. The results show that the evolution-based position-dependent encoding method PSSM achieved the best performance, and the structure-based and machine-learning encoding methods also show some potential for further application, the neural network based distributed representation of amino acids in particular may bring new light to this area. We hope that the review and assessment are useful for future studies in amino acid encoding.
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Methods like k-mer splitting have been developed to better interpret the biological grammar and semantics inherent in molecular data.
“Methods like k-mer splitting [39], among others [40], have been developed to better interpret the biological grammar and semantics inherent in molecular data.”
From Challenges in AI-driven Biomedical Multimodal Data Fusion and Analysis (2025) · cites this paper as [40]
Cites
Scikit-learn: Machine Learning in Python
Pedregosa, F., Varoquaux, G., Gramfort, A., Michel, V., Thirion, B., Grisel, O., Blondel, M., Müller, A., Nothman, J., Louppe, G., et al. (2012) · arXiv · doi:10.48550/arxiv.1201.0490 · Cited by 71,016 · see citing works
Distributed Representations of Words and Phrases and their Compositionality
Mikolov, T., Sutskever, I., Chen, K., Corrado, G., & Dean, J. (2013) · arXiv · doi:10.48550/arxiv.1310.4546 · Cited by 24,533 · see citing works
Kabsch, W., & Sander, C. (1983) · Biopolymers · doi:10.1002/bip.360221211 · Cited by 15,320 · see citing works
TensorFlow: Large-Scale Machine Learning on Heterogeneous Distributed Systems
Abadi, M., Agarwal, A., Barham, P., Brevdo, E., Chen, Z., Citro, C., Corrado, G. S., Davis, A., Dean, J., Devin, M., et al. (2016) · arXiv · doi:10.48550/arxiv.1603.04467 · Cited by 9,408 · see citing works
Principles that Govern the Folding of Protein Chains
Anfinsen, C. B. (1973) · Science · doi:10.1126/science.181.4096.223 · Cited by 7,096 · see citing works
Murzin, A. G., Brenner, S. E., Hubbard, T., & Chothia, C. (1995) · Journal of Molecular Biology · doi:10.1016/s0022-2836(05)80134-2 · Cited by 6,412 · see citing works
Amino acid substitution matrices from protein blocks.
Henikoff, S., & Henikoff, J. G. (1992) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.89.22.10915 · Cited by 6,218 · see citing works
UniProt: a hub for protein information
The UniProt Consortium (2015) · Nucleic Acids Research · doi:10.1093/nar/gku989 · Cited by 5,106 · see citing works
HHblits: lightning-fast iterative protein sequence searching by HMM-HMM alignment
Remmert, M., Biegert, A., Hauser, A., & Söding, J. (2012) · Nature Methods · doi:10.1038/nmeth.1818 · Cited by 2,288 · see citing works
PISCES: a protein sequence culling server
Wang, G., & Dunbrack, R. L. (2003) · Bioinformatics · doi:10.1093/bioinformatics/btg224 · Cited by 1,664 · see citing works
Miyazawa, S., & Jernigan, R. L. (1985) · Macromolecules · doi:10.1021/ma00145a039 · Cited by 1,588 · see citing works
Deep learning in bioinformatics
Min, S., Lee, B., & Yoon, S. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw068 · Cited by 1,514 · see citing works
Miyazawa, S., & Jernigan, R. L. (1996) · Journal of Molecular Biology · doi:10.1006/jmbi.1996.0114 · Cited by 1,231 · see citing works
Hydrophobicity of Amino Acid Residues in Globular Proteins
Rose, G. D., Geselowitz, A., Lesser, G. J., Lee, R., & Zehfus, M. H. (1985) · Science · doi:10.1126/science.4023714 · Cited by 1,176 · see citing works
AAindex: amino acid index database, progress report 2008
Kawashima, S., Pokarowski, P., Pokarowska, M., Koliński, A., Katayama, T., & Kanehisa, M. I. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm998 · Cited by 1,131 · see citing works
Continuous Distributed Representation of Biological Sequences for Deep Proteomics and Genomics
Asgari, E., & Mofrad, M. R. K. (2015) · PLoS ONE · doi:10.1371/journal.pone.0141287 · Cited by 817 · see citing works
Fox, N. K., Brenner, S. E., & Chandonia, J.-M. (2014) · Nucleic Acids Research · doi:10.1093/nar/gkt1240 · Cited by 762 · see citing works
Liu, B., Liu, F., Wang, X., Chen, J., Fang, L., & Chou, K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv458 · Cited by 723 · see citing works
Iterated profile searches with PSI-BLAST—a tool for discovery in protein databases
Altschul, S. F., & Koonin, E. V. (1998) · Trends in Biochemical Sciences · doi:10.1016/s0968-0004(98)01298-5 · Cited by 679 · see citing works
Critical assessment of methods of protein structure prediction (CASP) — round x
Moult, J., Fidelis, K. A., Kryshtafovych, A., Schwede, T. F., & Tramontano, A. L. (2013) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24452 · Cited by 673 · see citing works
Evaluation and improvement of multiple sequence methods for protein secondary structure prediction
Cuff, J. A., & Barton, G. J. (1999) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19990301)34:4 · Cited by 660 · see citing works
Use of the ‘Perceptron’ algorithm to distinguish translational initiation sites in E. coli
Stormo, G. D., Schneider, T. D., Gold, L., & Ehrenfeucht, A. (1982) · Nucleic Acids Research · doi:10.1093/nar/10.9.2997 · Cited by 651 · see citing works
Radzicka, A., & Wolfenden, R. V. (1988) · Biochemistry · doi:10.1021/bi00405a042 · Cited by 625 · see citing works
Protein Secondary Structure Prediction Using Deep Convolutional Neural Fields
Wang, S., Peng, J., Ma, J., & Xu, J. (2016) · Scientific Reports · doi:10.1038/srep18962 · Cited by 556 · see citing works
Amino Acid Properties and Consequences of Substitutions
Betts, M. J., & Russell, R. B. (2003) · doi:10.1002/0470867302.ch14 · Cited by 490 · see citing works
Automated assembly of protein blocks for database searching
Henikoff, S., & Henikoff, J. G. (1991) · Nucleic Acids Research · doi:10.1093/nar/19.23.6565 · Cited by 469 · see citing works
Amino‐Acid Properties and Consequences of Substitutions
Betts, M. J., & Russell, R. B. (2007) · doi:10.1002/9780470059180.ch13 · Cited by 452 · see citing works
Solving the protein sequence metric problem
Atchley, W. R., Zhao, J., Fernandes, A. D., & Drüke, T. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0408677102 · Cited by 452 · see citing works
Tanaka, S., & Scheraga, H. A. (1976) · Macromolecules · doi:10.1021/ma60054a013 · Cited by 437 · see citing works
Amino acid side chain parameters for correlation studies in biology and pharmacology
Fauchère, J., Charton, M., Kier, L. B., Verloop, A., & Pliška, V. (1988) · International journal of peptide & protein research · doi:10.1111/j.1399-3011.1988.tb01261.x · Cited by 386 · see citing works
Heffernan, R., Yang, Y., Paliwal, K. K., & Zhou, Y. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx218 · Cited by 358 · see citing works
Critical assessment of methods of protein structure prediction (CASP)—Round XII
Moult, J., Fidelis, K. A., Kryshtafovych, A., Schwede, T. F., & Tramontano, A. L. (2017) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.25415 · Cited by 327 · see citing works
Liu, B. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbx165 · Cited by 322 · see citing works
Learned protein embeddings for machine learning
Yang, K., Wu, Z., Bedbrook, C. N., & Arnold, F. H. (2018) · Bioinformatics · doi:10.1093/bioinformatics/bty178 · Cited by 316 · see citing works
Meiler, J., Zeidler, A., Schm�schke, F., & M�ller, M. (2001) · Journal of Molecular Modeling · doi:10.1007/s008940100038 · Cited by 271 · see citing works
Sixty-five years of the long march in protein secondary structure prediction: the final stretch?
Yang, Y., Gao, J., Wang, J., Heffernan, R., Hanson, J., Paliwal, K. K., & Zhou, Y. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw129 · Cited by 237 · see citing works
Skolnick, J., Godzik, A., Jaroszewski, L., & Koliński, A. (1997) · Protein Science · doi:10.1002/pro.5560060317 · Cited by 201 · see citing works
DeepSF: deep convolutional neural network for mapping protein sequences to folds
Hou, J., Adhikari, B., & Cheng, J. J. (2017) · Bioinformatics · doi:10.1093/bioinformatics/btx780 · Cited by 179 · see citing works
Damoulas, T., & Girolami, M. (2008) · Bioinformatics · doi:10.1093/bioinformatics/btn112 · Cited by 163 · see citing works
Riis, S. K., & Krogh, A. (1996) · Journal of Computational Biology · doi:10.1089/cmb.1996.3.163 · Cited by 157 · see citing works
Chen, J., Guo, M., Wang, X., & Liu, B. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw108 · Cited by 144 · see citing works
Liu, B., Wang, X., Lin, L., Dong, Q., & Wang, X. (2008) · BMC Bioinformatics · doi:10.1186/1471-2105-9-510 · Cited by 136 · see citing works
Self-citationReview and comparative assessment of sequence-based predictors of protein-binding residues
Zhang, J., & Kurgan, L. (2017) · Briefings in Bioinformatics · doi:10.1093/bib/bbx022 · Cited by 114 · see citing works
Environment-dependent residue contact energies for proteins
Zhang, C., & Kim, S. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.040573597 · Cited by 114 · see citing works
Protein Secondary Structure Prediction Using Cascaded Convolutional and Recurrent Neural NetworksPreprint
Li, Z., & Yu, Y. (2016) · arXiv (Cornell University) · doi:10.48550/arxiv.1604.07176 · Cited by 107 · see citing works
New techniques for extracting features from protein sequences
Wang, J., Ma, Q., Shasha, D. E., & Wu, C. H. (2001) · IBM Systems Journal · doi:10.1147/sj.402.0426 · Cited by 107 · see citing works
Hu, H.-J., Pan, Y. F., Harrison, R. W., & Tai, P. C. (2004) · IEEE Transactions on NanoBioscience · doi:10.1109/tnb.2004.837906 · Cited by 96 · see citing works
Protein structural alignments and functional genomics
Irving, J. A., Whisstock, J. C., & Lesk, A. M. (2001) · Proteins Structure Function and Bioinformatics · doi:10.1002/1097-0134(20010215)42:3 · Cited by 87 · see citing works
Asgari, E., McHardy, A. C., & Mofrad, M. R. K. (2019) · Scientific Reports · doi:10.1038/s41598-019-38746-w · Cited by 77 · see citing works
A study on protein sequence alignment quality
Elofsson, A. (2002) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.10043 · Cited by 77 · see citing works
Comparative n-gram analysis of whole-genome protein sequences
Ganapathiraju, M. K., Weisser, D. K., Rosenfeld, R., Carbonell, J. G., Reddy, R., & Klein‐Seetharaman, J. (2002) · International Conference on Human Language Technology Research · doi:10.3115/1289189.1289259 · Cited by 66 · see citing works
Tertiary and quaternary conformational changes in aspartate transcarbamylase: a normal mode study
Thomas, A. M., Hinsen, K., Field, M. J., & Pérahia, D. (1999) · Proteins Structure Function and Bioinformatics · doi:10.1002/(sici)1097-0134(19990101)34:1 · Cited by 64 · see citing works
Lin, K., May, A. C. W., & Taylor, W. R. (2002) · Journal of Theoretical Biology · doi:10.1006/jtbi.2001.2512 · Cited by 58 · see citing works
Zhou, J., Wang, H., Zhao, Z., Xu, R., & Lu, Q. (2018) · BMC Bioinformatics · doi:10.1186/s12859-018-2067-8 · Cited by 55 · see citing works
Xia, J., Peng, Z., Qi, D., Mu, H., & Yang, J. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw768 · Cited by 51 · see citing works
Machine Learning Techniques for Protein Secondary Structure Prediction:An Overview and Evaluation
Yoo, P. D., Zhou, B. B., & Zomaya, A. Y. (2008) · Current Bioinformatics · doi:10.2174/157489308784340676 · Cited by 47 · see citing works
A neural network model for the prediction of membrane‐spanning amino acid sequences
Lohmann, R., Schneider, G., Behrens, D., & Wrede, P. (1994) · Protein Science · doi:10.1002/pro.5560030924 · Cited by 46 · see citing works
Kinch, L. N., Li, W., Schaeffer, R. D., Dunbrack, R. L., Monastyrskyy, B., Kryshtafovych, A., & Grishin, N. V. (2016) · Proteins Structure Function and Bioinformatics · doi:10.1002/prot.24982 · Cited by 36 · see citing works
Xu, Y., Song, J., Wilson, C., & Whisstock, J. C. (2018) · Scientific Reports · doi:10.1038/s41598-018-26392-7 · Cited by 36 · see citing works
Using a neural network to backtranslate amino acid sequences
White, G., & Seffens, W. S. (1998) · Electronic Journal of Biotechnology · doi:10.2225/vol1-issue3-fulltext-5 · Cited by 33 · see citing works
Adaptive encoding neural networks for the recognition of human signal peptide cleavage sites
Jagla, B., & Schuchhardt, J. (2000) · Bioinformatics · doi:10.1093/bioinformatics/16.3.245 · Cited by 32 · see citing works
A large-scale comparative assessment of methods for residue–residue contact prediction
Wuyun, Q., Zheng, W. H., Peng, Z., & Yang, J. (2016) · Briefings in Bioinformatics · doi:10.1093/bib/bbw106 · Cited by 28 · see citing works
Mining for class-specific motifs in protein sequence classification
Srinivasan, S., Vural, S., King, B. R., & Guda, C. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-96 · Cited by 24 · see citing works
Deep Recurrent Conditional Random Field Network for Protein Secondary Prediction
Johansen, A. R., Sønderby, C. K., Sønderby, S. K., & Winther, O. (2017) · ACM International Conference on Bioinformatics, Computational Biology, and Health Informatics (ACM-BCB) · doi:10.1145/3107411.3107489 · Cited by 23 · see citing works
Reaching optimized parameter set: protein secondary structure prediction using neural network
Dongardive, J., & Abraham, S. (2016) · Neural Computing and Applications · doi:10.1007/s00521-015-2150-2 · Cited by 16 · see citing works
Amino acid encoding schemes for machine learning methods
Zamani, M., & Kremer, S. C. (2011) · IEEE International Conference on Bioinformatics and Biomedicine Workshops (BIBMW) · doi:10.1109/bibmw.2011.6112394 · Cited by 16 · see citing works
A novel knowledge-based approach to design inorganic-binding peptides
Oren, E., Tamerler, C., Sahin, D., Hnilova, M., Şeker, U., Sarikaya, M., & Samudrala, R. (2007) · Bioinform. · doi:10.1093/bioinformatics/btm436 · Cited by 10 · see citing works
Applications of nonlinear system identification to protein structural prediction
Robert, D. (2000) · DSpace@MIT (Massachusetts Institute of Technology) · Cited by 8 · see citing works
Parallel protein secondary structure prediction based on neural networks
Zhong, W., Altun, G., Tian, X., Harrison, R. W., Tai, P. C., & Pan, Y. F. (2005) · Annual International Conference of the IEEE Engineering in Medicine and Biology Society (EMBC) · doi:10.1109/iembs.2004.1403842 · Cited by 5 · see citing works
Flagged first, then by citations
1 of the 70 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Dinu, A., & Apetrei, C. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23031218 · Cited by 84 · see citing works
“Compared with other amino acids, Phe, Tyr, and Trypt are of particular importance to the central nervous system [53].”
BackgroundMachine learning-driven multifunctional peptide engineering for sustained ocular drug delivery
Hsueh, H. T., Chou, R. T., Rai, U., Liyanage, W., Kim, Y. C., Appell, M. B., Pejavar, J., Leo, K. T., Davison, C., Kolodziejski, P., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-38056-w · Cited by 81 · see citing works
Challenges in AI-driven Biomedical Multimodal Data Fusion and Analysis
Liu, J., Cen, X., Yi, C., Wang, F.-A., Ding, J., Cheng, J., Wu, Q., Gai, B., Zhou, Y., He, R., et al. (2025) · Genomics, Proteomics & Bioinformatics · doi:10.1093/gpbjnl/qzaf011 · Cited by 75 · see citing works
Chen, X., Li, C., Bernards, M. T., Shi, Y., Shao, Q., & He, Y. (2021) · Molecular Systems Design & Engineering · doi:10.1039/d0me00161a · Cited by 56 · see citing works
Xie, Z., Deng, X., & Shu, K. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21020467 · Cited by 55 · see citing works
EnACP: An Ensemble Learning Model for Identification of Anticancer Peptides
Ge, R., Feng, G., Jing, X., Zhang, R., Wang, P., & Wu, Q. (2020) · Frontiers in Genetics · doi:10.3389/fgene.2020.00760 · Cited by 51 · see citing works
“For feature representation, if the features of peptide sequences are well-extracted, it will be easier to precisely predict the ACPs (Jing et al., 2019).”
BackgroundSelf-citationAn analysis of protein language model embeddings for fold prediction
Villegas-Morcillo, A., Gomez, A. M., & Sanchez, V. (2022) · Briefings in Bioinformatics · doi:10.1093/bib/bbac142 · Cited by 46 · see citing works
Deep learning for protein secondary structure prediction: Pre and post-AlphaFold
Ismi, D. P., Pulungan, R., & Afiahayati (2022) · Computational and Structural Biotechnology Journal · doi:10.1016/j.csbj.2022.11.012 · Cited by 53 · see citing works
“Several studies focused on proposing new feature representations, such as new amino acid encoding schemes [46–48], and other features such as protein language models [49,50].”
BackgroundRio, A. L.-D., Martin, M. J., Perera-Lluna, A., & Saidi, R. (2020) · Scientific Reports · doi:10.1038/s41598-020-71450-8 · Cited by 53 · see citing works
KinasePhos 3.0: Redesign and Expansion of the Prediction on Kinase-Specific Phosphorylation Sites
Ma, R., Li, S., Li, W., Yao, L., Huang, H., & Lee, T.-Y. (2022) · Genomics Proteomics & Bioinformatics · doi:10.1016/j.gpb.2022.06.004 · Cited by 43 · see citing works
Barbero-Aparicio, J. A., Olivares-Gil, A., Diez, J. J. R., García-Osorio, C., & Díez-Pastor, J. (2023) · Information Fusion · doi:10.1016/j.inffus.2023.102035 · Cited by 33 · see citing works
Machine learning in predictive biocatalysis: A comparative review of methods and applications
Tripathi, N., Hérisson, J., & Faulon, J. (2025) · Biotechnology Advances · doi:10.1016/j.biotechadv.2025.108698 · Cited by 36 · see citing works
Predicting aggregate morphology of sequence-defined macromolecules with recurrent neural networks
Bhattacharya, D., Kleeblatt, D. C., Statt, A., & Reinhart, W. F. (2022) · Soft Matter · doi:10.1039/d2sm00452f · Cited by 35 · see citing works
Pundi, A., & Chang, C. (2023) · Journal of environmental chemical engineering · doi:10.1016/j.jece.2023.110346 · Cited by 35 · see citing works
Artificial intelligence based methods for hot spot prediction
Ovek, D., Abali, Z., Zeylan, M. E., Keskin, Ö., Gürsoy, A., & Tunçbağ, N. (2021) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2021.11.003 · Cited by 36 · see citing works
A Comprehensive Survey of Deep Learning Techniques in Protein Function Prediction
Dhanuka, R., Singh, J. P., & Tripathi, A. (2023) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2023.3247634 · Cited by 34 · see citing works
“The majority of models used for PFP are trained by using features generated from protein sequences [11], [24], [25], [26], [27], [28], [29], [30].”
BackgroundMethodAnteghini, M., dos Santos, V. A. P. M., & Saccenti, E. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22126409 · Cited by 30 · see citing works
Wang, X. R., Ding, Z., Wang, R., & Lin, X. (2023) · Briefings in Bioinformatics · doi:10.1093/bib/bbac631 · Cited by 33 · see citing works
ME-ACP: Multi-view neural networks with ensemble model for identification of anticancer peptides
Feng, G., Yao, H., Li, C., Liu, R., Huang, R., Fan, X., Ge, R., & Miao, Q. (2022) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2022.105459 · Cited by 29 · see citing works
Finding functional motifs in protein sequences with deep learning and natural language models
Savojardo, C., Martelli, P. L., & Casadio, R. (2023) · Current Opinion in Structural Biology · doi:10.1016/j.sbi.2023.102641 · Cited by 29 · see citing works
Alakuş, T. B., & Türkoğlu, İ. (2021) · Interdisciplinary Sciences Computational Life Sciences · doi:10.1007/s12539-020-00405-4 · Cited by 28 · see citing works
“It is generally used in the prediction of protein interactions and classification of protein functions [33, 34].”
BackgroundMethodDeep learning program to predict protein functions based on sequence information
Ko, C. W., Huh, J., & Park, J. (2022) · MethodsX · doi:10.1016/j.mex.2022.101622 · Cited by 21 · see citing works
“Recently, several research groups try to use machine-learning based encoding methods instead of manually define methods to solve the problems [7] .”
BackgroundA Semi-Supervised Autoencoder-Based Approach for Protein Function Prediction
Dhanuka, R., Tripathi, A., & Singh, J. P. (2022) · IEEE Journal of Biomedical and Health Informatics · doi:10.1109/jbhi.2022.3163150 · Cited by 18 · see citing works
Application of Sequence Embedding in Protein Sequence-Based Predictions
Ibtehaz, N., & Kihara, D. (2022) · WORLD SCIENTIFIC eBooks · doi:10.1142/9789811258589_0002 · Cited by 16 · see citing works
Liang, T., Sun, Z., Ishima, R., Xie, X., Xue, Y., Li, W., & Feng, Z. (2025) · Research · doi:10.34133/research.0674 · Cited by 14 · see citing works
“Following the works of Jing et al. [ 35 ], the blastp pro gram was used to identify and exclude homology data (BLAST evalue < 0.001).”
InfluentialAn Innovative Bispectral Deep Learning Method for Protein Family Classification
Abu-Qasmieh, I. F., Fahoum, A. S. A., Alquran, H., & Zyout, A. (2023) · Computers, materials & continua/Computers, materials & continua (Print) · doi:10.32604/cmc.2023.037431 · Cited by 13 · see citing works
Ryu, J., Komoto, Y., Ohshiro, T., & Taniguchi, M. (2022) · Chemistry - An Asian Journal · doi:10.1002/asia.202200179 · Cited by 13 · see citing works
Yang, Z., Wang, Y., Ni, X., & Yang, S. (2023) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2023.127390 · Cited by 12 · see citing works
A Novel Multi-Stage Bispectral Deep Learning Method for Protein Family Classification
Fahoum, A. S. A., Zyout, A., Alquran, H., & Abu-Qasmieh, I. F. (2023) · Computers, materials & continua/Computers, materials & continua (Print) · doi:10.32604/cmc.2023.038304 · Cited by 11 · see citing works
Deep learning methods for protein representation and function prediction: A comprehensive overview
Wang, M., Nie, Z., He, Y., Vasilakos, A. V., Cheng, Q. S., & Ren, Z. (2025) · Engineering Applications of Artificial Intelligence · doi:10.1016/j.engappai.2025.110977 · Cited by 11 · see citing works
Cao, L., Zhang, Q., Song, H., Lin, K., & Pang, E. (2022) · iScience · doi:10.1016/j.isci.2022.105345 · Cited by 11 · see citing works
“Then, we utilized the most common method for encoding mRNA sequences, one-hot encoding (Jing et al., 2020).”
Comparative study of encoded and alignment-based methods for virus taxonomy classification
Shaukat, M. A., Nguyen, T. T., Hsu, E. B., Yang, S. S., & Bhatti, A. (2023) · Scientific Reports · doi:10.1038/s41598-023-45461-0 · Cited by 10 · see citing works
A systematic review on the state-of-the-art strategies for protein representation
Yue, Z., Yan, T., Xu, H., Liu, Y., Hong, Y., Chen, G.-X., Xie, T., & Tao, L. (2022) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2022.106440 · Cited by 10 · see citing works
Alquran, H., Fahoum, A. S. A., Zyout, A., & Abu-Qasmieh, I. F. (2023) · PLoS ONE · doi:10.1371/journal.pone.0295805 · Cited by 10 · see citing works
“As mentioned above, the procedure is commonly referred to as a binary encoding technique [27].”
BackgroundMethodInfluentialIllig, A.-M., Siedhoff, N. E., Schwaneberg, U., & Davari, M. D. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.07.495081 · Cited by 10 · see citing works
“Hence, diverse strategies have been developed for encoding that can mainly be divided into amino acid-specific [15, 17–21] and sequence-specific encoding [22–25].”
BackgroundNetwork Intrusion Detection Based on Amino Acid Sequence Structure Using Machine Learning
Ibaisi, T. A., Kühn, S., Kaiiali, M., & Kazim, M. (2023) · Electronics · doi:10.3390/electronics12204294 · Cited by 13 · see citing works
Li, W., Yang, L., Qiu, Y., Yuan, Y., Li, X., & Meng, Z. (2022) · BMC Bioinformatics · doi:10.1186/s12859-022-04889-3 · Cited by 8 · see citing works
“The primary sequence is represented by 20 amino acid letters, and this representation cannot be processed directly and needs to be converted to numbers [31].”
BackgroundMachine learning approaches for predicting protein-ligand binding sites from sequence data
Vural, O., & Jololian, L. (2025) · Frontiers in Bioinformatics · doi:10.3389/fbinf.2025.1520382 · Cited by 8 · see citing works
MFA-DTI: Drug-target interaction prediction based on multi-feature fusion adopted framework
Chen, S., Li, M., & Semenov, I. (2024) · Methods · doi:10.1016/j.ymeth.2024.02.008 · Cited by 7 · see citing works
How did we get there? AI applications to biological networks and sequences
Anteghini, M., Gualdi, F., & Oliva, B. (2025) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2025.110064 · Cited by 9 · see citing works
Wang, G.-P., Ye, X.-L., & Zhou, S. (2024) · The European Physical Journal Plus · doi:10.1140/epjp/s13360-024-05415-5 · Cited by 4 · see citing works
A multimodal model for protein function prediction
Mao, Y., Xu, W., Shun, Y., Chai, L., Xue, L., Yang, Y., & Li, M. (2025) · Scientific Reports · doi:10.1038/s41598-025-94612-y · Cited by 6 · see citing works
HybAVPnet: A Novel Hybrid Network Architecture for Antiviral Peptides Prediction
Ge, R., Xia, Y., Jiang, M., Jia, G., Jing, X., Li, Y., & Cai, Y. (2024) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2024.3385635 · Cited by 6 · see citing works
“Four kinds of features were generated according to autocorrelation: auto covariance (feature-AC), auto-cross covariance (ACC), cross covariance (feature-CC), and physicochemical distance transformation (PDT) [46].”
BackgroundSelf-citationHybAVPnet: a novel hybrid network architecture for antiviral peptides identificationPreprint
Ge, R., Xia, Y., Jiang, M., Jia, G., Jing, X., Li, Y., & Cai, Y. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.06.10.495721 · Cited by 6 · see citing works
“To better interpret the feature representation between the sub models, we adopted t-distributed stochastic neighborhood embedding (t-SNE) to visualize and compare the feature space distribution on V 60P+45N and V 60P+60N datasets(Kobak and Linderman, 2021).”
MethodSelf-citationJiang, S., Su, Z., Bloodworth, N. C., Liu, Y., Martina, C. E., Harrison, D. G., & Meiler, J. (2025) · PLoS ONE · doi:10.1371/journal.pone.0314833 · Cited by 5 · see citing works
Agrawal, S., Sisodia, D. S., & Nagwani, N. K. (2021) · Medical & Biological Engineering & Computing · doi:10.1007/s11517-021-02436-5 · Cited by 5 · see citing works
“On the basis of amino acid properties, feature extraction techniques have been defined and applied [31]. iFeature web server gives facility to extract sequence-and physicochemical-based features [30] while POSSUM web server provides a bioinformatics toolkit for generating numerical features based…”
MethodProtein function prediction using functional inter-relationship
Dhanuka, R., & Singh, J. P. (2021) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2021.107593 · Cited by 5 · see citing works
A Novel Capsule Network with Attention Routing to Identify Prokaryote Phosphorylation Sites
Wang, S., Zhang, L., Yang, R., & Zhao, Y. (2022) · Biomolecules · doi:10.3390/biom12121854 · Cited by 5 · see citing works
“The physicochemical properties of amino acids have long been pivotal in protein-related research [39].”
BackgroundAlakuş, T. B., & Türkoğlu, İ. (2020) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2020.102359 · Cited by 5 · see citing works
Lu, J., Chen, H., & Qiu, J. (2024) · IEEE Access · doi:10.1109/access.2024.3427792 · Cited by 4 · see citing works
“This encoding effectively represents the specific type of each amino acid [45].”
BackgroundWang, C., Jiang, Q., Yu, D., Guan, J., Chen, Z., Lu, X., Yan, B., Qin, J., Liu, Y., & Wang, J. (2026) · Briefings in Bioinformatics · doi:10.1093/bib/bbag321 · Cited by 4 · see citing works
“The 20 standard amino acids were mapped to integers 0–19, and a special padding character ( ∗ ), used for handling sequence boundaries, was encoded as 20 [ 29].”
Alakuş, T. B., & Türkoğlu, İ. (2021) · Studies in systems, decision and control · doi:10.1007/978-3-030-72834-2_18 · Cited by 4 · see citing works
Protein sequence analysis in the context of drug repurposing
Sánchez, N. G., Carro, E. U., Santamaría, L. P., & Rodríguez‐González, A. (2024) · BMC Medical Informatics and Decision Making · doi:10.1186/s12911-024-02531-1 · Cited by 5 · see citing works
“There are two types of methods: (i) direct encoding creates a vector of numerical features for each position or token in a sequence, whereas (ii) indirect encoding works with an established number of features for the encoded sequences [20].”
MethodZhang, Z., & Wang, L. (2020) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2020.1821778 · Cited by 4 · see citing works
“This encoding scheme is often used to convert nucleotide sequences with an equal length (Hayouka et al., 2017; Jing et al., 2019).”
Method2020 Index IEEE/ACM Transactions on Computational Biology and Bioinformatics Vol. 17
(2021) · IEEE Transactions on Computational Biology and Bioinformatics · doi:10.1109/tcbb.2020.3047571 · Cited by 4 · see citing works
Multiview and Decision Fusion in Stacking Ensemble To Predict Anti-Cancer Peptides
Kumar, A., & Singh, D. (2024) · OPJU International Technology Conference on Smart Computing for Innovation and Advancement in Industry (OTCON) · doi:10.1109/otcon60325.2024.10687578 · Cited by 3 · see citing works
“Hydrophilicity, along with other physicochemical features, is thought to impact the organization of protein selfassembly substantially [18].”
Backgroundi2APP: A Two-Step Machine Learning Framework For Antiparasitic Peptides Identification
Jiang, M., Zhang, R., Xia, Y., Jia, G., Yin, Y., Wang, P., Wu, J., & Ge, R. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.884589 · Cited by 3 · see citing works
“In this study, we take out a fragment with three or fi ve amino acids at the N-terminus or C-terminus of a peptide sequence, and use 12 types of feature extraction method for this fragment (Jing et al., 2019).”
MethodIllig, A.-M., Siedhoff, N. E., Davari, M. D., & Schwaneberg, U. (2024) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.4c00704 · Cited by 3 · see citing works
MCTASmRNA: A deep learning framework for alternative splicing events classification
Zheng, J.-Y., Gao, J., Gao, F.-H., Ren, S.-N., Zhu, C., Xie, J., Li, Z., Yin, W., Xia, X., Li, Y., et al. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.139941 · Cited by 3 · see citing works
Agrawal, S., Sisodia, D. S., & Nagwani, N. K. (2021) · Iranian Journal of Science and Technology Transactions A Science · doi:10.1007/s40995-021-01134-z · Cited by 3 · see citing works
Artificial intelligence-driven protease cleavage site prediction: Advances and challenges
Yang, L., Ji, Z., Liu, C., Fan, H., Yang, X., & Shi, C. (2026) · Biotechnology Advances · doi:10.1016/j.biotechadv.2026.108867 · Cited by 2 · see citing works
Kaur, A., Chitre, A., Wanjale, K. H., Kumar, P., Miah, S., & Alguno, A. C. (2022) · BioMed Research International · doi:10.1155/2022/2273648 · Cited by 2 · see citing works
“Literature [16] sets a threshold based on the weighted density of the complex and the size of the cluster.”
RetractedQiao, N., & Qi, Z. (2024) · Computers in Biology and Medicine · doi:10.1016/j.compbiomed.2024.109328 · Cited by 2 · see citing works
Zhu, Y.-H., Zhu, S., Yu, X., Yan, H., Liu, Y., Xie, X., Yu, D., & Ye, R. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf420 · Cited by 1 · see citing works
“This could be implemented by extracting handcrafted feature representations (e.g. k-mer k-mer sequence encoding [14] and position-specific scoring matrix [15]) from protein sequences, which are then processed with statistical machine learning algorithms (e.g. support vector machine [16] and random…”
Zhao, Y., Liu, X., Xie, P., Guan, J., Zhao, Z., Wang, J., Lee, T., Chiang, Y.-C., Wei, L., Liu, X., et al. (2026) · Journal of Cheminformatics · doi:10.1186/s13321-026-01183-9 · Cited by 1 · see citing works
“…features and those derived from five widely used traditional protein descriptors: amino acid composition (AAC), pseudo-amino acid composition (PAAC), composition of k-spaced amino acid group pairs (CKSAAGP), dipeptide composition (DPC), and physico-chemical property-based encoding (PHYC) [47].”
Lee, W.-H., Dumontet, L., Jung, K., Lee, H. J., Thapa, G., Oh, T., & Kang, M. (2026) · Applied and Environmental Microbiology · doi:10.1128/aem.01586-25 · Cited by 2 · see citing works
GLTM: A Global-Local Attention LSTM Model to Locate Dimer Motif of Single-Pass Membrane Proteins
Ma, Q., Zou, K., Zhang, Z., & Yang, F. (2022) · Frontiers in Genetics · doi:10.3389/fgene.2022.854571 · Cited by 1 · see citing works
“Standard one-hot encoding used independent binary vector dimensions to respectively represent twenty standard amino acids (Jing et al., 2020).”
MethodPhylogenetic Analysis: A Novel Method of Protein Sequence Similarity Analysis
Li, W., Yang, L., Meng, Z., Qiu, Y., Wang, P. S. P., & Li, X. (2022) · International Journal of Pattern Recognition and Artificial Intelligence · doi:10.1142/s0218001422580071 · Cited by 1 · see citing works
Prediction of human protein functions with protein mapping techniques and deep learning model
Alakuş, T. B., & Türkoğlu, İ. (2022) · Pamukkale University Journal of Engineering Sciences · doi:10.5505/pajes.2021.51261 · Cited by 1 · see citing works
Li, W., Yang, L., & Meng, Z. (2021) · Asian Conference on Artificial Intelligence Technology (ACAIT) · doi:10.1109/acait53529.2021.9731147 · Cited by 1 · see citing works
Yan, Q., Pan, S., Cheng, Z., & Ding, Y. (2025) · Future Generation Computer Systems · doi:10.1016/j.future.2025.107819 · Cited by 1 · see citing works
Kumar, A., & Singh, D. (2025) · Expert Systems with Applications · doi:10.1016/j.eswa.2025.128093 · Cited by 1 · see citing works
Milchevskiy, Y. V., Milchevskaya, V., & Kravatsky, Y. V. (2023) · Molecular Biology · doi:10.31857/s0026898423010093 · Cited by 1 · see citing works
Milchevskiy, Y. V., Milchevskaya, V., & Kravatsky, Y. V. (2023) · Molecular Biology · doi:10.1134/s0026893323010089 · Cited by 1 · see citing works
“Current methods to form predictors for protein sequences have been described in detail and classified in a review [12].”
MethodEffect of Sequence Padding on the Performance of Protein-Based Deep Learning ModelsPreprint
Rio, A. L.-D., Martin, M. J., Perera-Lluna, A., & Saidi, R. (2020) · doi:10.21203/rs.2.21336/v1 · Cited by 2 · see citing works
“A comprehensive review and assessment on different amino acid encoding methods [19] shows that position specific scoring matrix (PSSM), an evolution-based position dependent methodology, achieves the best performance on protein secondary structure prediction and protein fold recognition tasks.”
BackgroundMethodAI predicted TCR-pMHC structures differentiate immune interactionsPreprint
Robben, M. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.24.707744 · Cited by 1 · see citing works
“To combine sequence and structure information we tested different encoding methods 34 in a different 2D CNN developed on the Pytorch library.”
Ge, R., Feng, G., Wang, P., & Miao, Q. (2020) · IEEE International Conference on Bioinformatics and Biomedicine (BIBM) · doi:10.1109/bibm49941.2020.9313358
“There are 18 kinds of protein features and 13 kinds of amino acid features in total used in this study [16, 17].”
MethodGLMFD: An Attention-Based CNN-LSTM Model for Transmembrane Domains Localization
Ma, Q., Yang, F., Zou, K., & Zhang, Z. (2022) · International Conference on Electronic Communication and Artificial Intelligence (ICECAI) · doi:10.1109/iwecai55315.2022.00098
Chakraborty, R., & Hasija, Y. (2022) · Soft Computing · doi:10.1007/s00500-022-07085-w
“The most difficult part of the NLP pipeline is feature extraction and finding out the relationships between words and letters through their numerical representations (Jing et al. 2019).”
BackgroundMir, R. A., Shafi, S. M., & Zargar, S. M. (2023) · Elsevier eBooks · doi:10.1016/b978-0-323-99045-5.00006-9
REC protein family expansion by the emergence of a new signaling pathway
Garber, M. E., Frank, V., Kazakov, A. E., Incha, M. R., Nava, A. A., Zhang, H., Valencia, L. E., Keasling, J. D., Rajeev, L., & Mukhopadhyay, A. (2023) · mBio · doi:10.1128/mbio.02622-23
“We then encoded the sequences into a discrete variable vector representation (62), by encoding each amino acid into a 21-dimensional zero vector (one dimension for each possible amino acid and a gap character), except for the index representing the amino acid, which is set to 1.”
MethodErten, M. (2024) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2024.2302937
“For example, protein sequences can be thought of as sentences, and the amino acid or polypeptide chain can be considered as words (Jing et al., 2020).”
CRULoc: A protein subcellular localization prediction model based on BiGRU and CNN
Lu, Y. (2024) · International Conference on Computer Information Science and Application Technology (CISAT) · doi:10.1109/cisat62382.2024.10695442
“These methods make full use of evolutionary information generated from multiple sequence alignments (MSAs), highlighting the reliability of evolutionary information from related protein families in MSAs for predictions [4].”
MethodMultiview Learning and Decision Fusion Based Ensemble to Predict Anti-Cancer Peptide
Kumar, A., & Singh, D. (2024) · International Conference on Pioneering Developments in Computer Science & Digital Technologies (IC2SDT) · doi:10.1109/ic2sdt62152.2024.10695980
“The hydrophilic nature of proteins, along with other physicochemical characteristics, is believed to influence the organization of protein self-assembly [17] significantly.”
BackgroundJiang, S., Su, Z., Bloodworth, N. C., Liu, Y., Martina, C. E., Harrison, D. G., & Meiler, J. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.11.19.624425
Prediction of Protein Secondary Structure Using a Hybrid Convolutional Blocks with GRU Units
Yang, S., & Chen, X. (2024) · Frontiers in Computing and Intelligent Systems · doi:10.54097/k8rmxp27
Nguyen, H. T., & Brissette, C. A. (2026) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1014407
“Each sequence was transformed to a binary feature matrix using one-hot encoding, a standard orthogonal encoding technique for aa sequences [60].”
Plastic-hydrolytic enzyme classification using explainable deep learningPreprint
Lee, W.-H., Dumontet, L., Jung, K., Lee, H. J., Thapa, G., Oh, T., & Kang, M. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.14.664602
“17 20 However, reliance on sequence similarity alone presents critical limitations on characterizing plastic-degrading enzymes.”
Additional file 1 of Protein sequence analysis in the context of drug repurposing
Sánchez, N. G., Carro, E. U., Prieto-Santamaría, L., & Rodríguez‐González, A. (2024) · Figshare · doi:10.6084/m9.figshare.26719884
Alsaraaj, E. G., Ibrahim, T. Z., & Alomari, A. (2025) · IOP Conference Series Earth and Environmental Science · doi:10.1088/1755-1315/1549/1/012162
“These amino acids have a key role in flavor creation [16], some of essential amino acids like lysine and histidine directly damage pathogen cell membranes, causing the leaking of essential components and growth suppression because their positive charge interacts with negatively charged bacterial…”
Balachandran, P., & Bhadra, P. (2026) · Lecture notes in networks and systems · doi:10.1007/978-3-032-13806-4_6
What Kinds of Machine Learning Models Might Guide the Design of Biomedical Nanomaterials?
Wang, X., Lin, X., Wu, T., Sun, Y., Guan, Y., Mao, C., & Wan, M. (2026) · ACS Nano Medicine · doi:10.1021/acsnanomed.5c00112
Serage, R., Nyirenda, C., Omomule, T. G., Christoffels, A. G., & Anderson, D. E. (2026) · Bioinformatics and Biology Insights · doi:10.1177/11779322251415123
“Several encoding meth-ods are available which use mathematical transformations as well as pre-computed embeddings, 87-91 however, FCGR is an underrepresented feature encoding method, shown to achieve good metrics in our study.”
Artificial Intelligence Applications in Macromolecular Research: A Comprehensive Review
Rani, L., Sarangi, P. K., Sahoo, A. K., & Agrawal, A. K. (2026) · Macromolecular Symposia · doi:10.1002/masy.70230
Li, P., Wang, W., & Yu, D.-J. (2026) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6c00101
Ng, Y.-L., Wang, X., Li, Y., Huang, J., Lai, H. M., Chan, J. Y. K., NG, B. K. W., Ko, H., & Kwok, K. (2026) · GigaScience · doi:10.1093/gigascience/giag056
“To transform the twenty standard amino acid residues using the one-hot encoding [ 67 ] method, a node feature (sparse) matrix, X ∈ { 0 , 1 } L × 20 is formed, where each matrix column denotes one amino acid type and L is the number of residues in the protein sequence.”
An optimized multi-view deep ensemble for identifying anti-viral and anti-corona peptides
Kumar, A., & Singh, D. (2026) · Applied Soft Computing · doi:10.1016/j.asoc.2026.115523
Carbamate post-translational modifications: bridging CO2 biology and protein regulation
Dewhurst, R. M., Weston, G. M. I., & Cann, M. J. (2026) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2026.09.014
- Authors
- Jing, X., Dong, Q., Hong, D., & Lu, R.
- Affiliations
- Fudan University (CN)
- East China Normal University (CN)
- Venue
- IEEE/ACM Transactions on Computational Biology and Bioinformatics
- Published
- 2020-11-01
- Volume
- 17
- Issue
- 6
- Pages
- 1918-1931
- ISSN
- 1545-5963 (ISSN-L)
- 1557-9964
- 2374-0043
- OpenAlex
- W2940438782
- Cited by
- 97
- References
- 70
- Citations by year
- 2026: 14 · 2025: 14 · 2024: 13 · 2023: 16 · 2022: 23 · 2021: 10 · 2020: 7
- FWCI
- 0.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- Locations
- IEEE Transactions on Computational Biology and Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China (61672234, U1401256, U1711262, 61402177)
- National Key Research and Development Program of China (2016YFB1000905)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Structure and Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Machine Learning in Bioinformatics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fractal and DNA sequence analysis
- Keywords
- amino acid encoding, protein sequence representation, secondary structure prediction, protein fold recognition, position weight matrices, physicochemical properties
- MeSH terms
- Algorithms, Amino Acid Sequence, Amino Acids, Proteins, Protein Structure, Secondary, Protein Folding, Computational Biology, Sequence Analysis, Protein
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