AI Chat Paper
Note: Please note that the following content is generated by AMiner AI. SciOpen does not take any responsibility related to this content.
{{lang === 'zh_CN' ? '文章概述' : 'Summary'}}
{{lang === 'en_US' ? '中' : 'Eng'}}
Chat more with AI
PDF (13.7 MB)
Collect
Submit Manuscript AI Chat Paper
Show Outline
Outline
Show full outline
Hide outline
Outline
Show full outline
Hide outline
Research Article | Open Access

Mining anti-hypertensive peptides in animal food through deep learning: a case study of gastrointestinal digestive products of royal jelly

Fei Pan1,§Dongliang Liu2,§Tuohetisayipu Tuersuntuoheti3,4Huadong Xing2Zehui Zhu3Yu Fang1Lei Zhao3Liang Zhao3Xiangxin Li1Yingying Le2( )Qiannan Hu2( )Wenjun Peng1( )Wenli Tian1( )
State Key Laboratory of Resource Insects, Institute of Apicultural Research, Chinese Academy of Agricultural Sciences, Beijing 100093, China
CAS Key Laboratory of Computational Biology, CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai 200031, China
Beijing Advanced Innovation Center for Food Nutrition and Human Health, Beijing Engineering and Technology Research Center of Food Additives, Beijing Technology and Business University, Beijing 100048, China
Pony Testing International Group Co., Ltd., Beijing 100095, China

§These authors contributed equally to this work.

Show Author Information

Abstract

To shorten the complex and time-consuming process of the identification method of the traditional food angiotensin-I-converting enzyme (ACE-I) inhibitory peptides, we propose AHTPeptideFusion based on a segmented fusion with the protein language model and deep learning. The statistical analysis found that hydrophobic amino acids, N-terminal valine is a dominant amino acid in the activity of ACE-I inhibitory peptides. In 12 machine learning (ML) algorithms, the transformer outperformed the other 11 models, with the best performance in predicting short and medium peptides. In the external dataset, AHTPeptideFusion fused by transformer and random forest (RF) showed excellent performance (accuracy > 0.9) in predicting ACE-I inhibitory peptides with lengths ranging from 2 to 15 amino acid residues and different activity distributions, and the reliability and accuracy of AHTPeptideFusion was demonstrated by synthetic peptide and ACE-I inhibition experiments. In addition, hydrogen bonding and electrostatic interaction between 4 synthetic peptides and active residues of ACE-I were found by molecular docking. To further explore the ACE-I inhibitory peptides from animal-derived foods, we established an automated pipeline consisting of the trinity of proteomics, virtual enzymatic digestion and AHTPeptideFusion, and tapped the ACE-I inhibitory peptide released from royal jelly after digestion in the gastrointestinal tract. In conclusion, this computational pipeline will become a powerful screening tool for active peptides from animal-derived foods, which can help food scientists accelerate the mining and design of active peptides from animal-derived foods. Overall, AHTPeptideFusion will be a powerful ACE-I inhibitor peptide prediction tool, it can help food scientists accelerate the mining and design of ACE-I inhibitory peptides.

Electronic Supplementary Material

Download File(s)
FSAP-2024-0008_ESM.pdf (3.5 MB)

References

[1]
World health statistics 2023: monitoring health for the SDGs, sustainable development goals, Geneva: World Health Organization (2023). Licence: CC BY-NC-SA 3.0 IGO. Available from: https://www.who.int/publications/i/item/9789240074323.
[2]

R. M. Touyz, Hypertension 2022 update: focusing on the future, Hypertension 79 (2022) 1559–1562. https://doi.org/10.1161/HYPERTENSIONAHA.122.19564.

[3]

B. Baudin, New aspects on angiotensin-converting enzyme: from gene to disease, Clin. Chem. Lab. Med. 40(3) (2002) 256–265. https://doi.org/10.1515/CCLM.2002.042.

[4]

G. Kalyan, V. Junghare, M. F. Khan, et al., Anti-hypertensive peptide predictor: a machine learning-empowered web server for prediction of food-derived peptides with potential angiotensin-converting enzyme-I inhibitory activity, J. Agric. Food. Chem. 69(49) (2021) 14995–15004. https://doi.org/10.1021/acs.jafc.1c04555.

[5]
Q. Wu, F. J. Luo, X. L. Wang, et al., Angiotensin I-converting enzyme inhibitory peptide: an emerging candidate for vascular dysfunction therapy. Crit. Rev. Biotechnol. 42(5) (2022) 736–755. https://doi.org/10.1080/07388551.2021.1948816.
[6]

Y. D. Hu, Q. H. Xi, J. Kong, et al., Angiotensin-I-converting enzyme (ACE)-inhibitory peptides from the collagens of monkfish ( Lophius litulon) swim bladders: isolation, characterization, molecular docking analysis and activity evaluation, Mar. Drugs 21 (2023) 516. https://doi.org/10.3390/md21100516.

[7]
S. K. Suo, S. L. Zheng, C. F. Chi, et al., Novel angiotensin-converting enzyme inhibitory peptides from tuna byproducts-milts: preparation, characterization, molecular docking study, and antioxidant function on H2O2-damaged human umbilical vein endothelial cells, Front. Nutr. 9 (2022). https://doi.org/10.3389/fnut.2022.957778.
[8]
S. H. Ferreira, A bradykinin-potentiating factor (BPF) present in the venom of Bothrops jararaca. Br. J. Pharmacol. 24 (1965) 163–169. https://doi.org/10.1111/j.1476-5381.1965.tb02091.x.
[9]

S. H. Ferreira, D. C. Bartelt, L. J. Greene, Isolation of bradykinin-potentiating peptides from Bothrops jararaca venom, Biochemistry 9(13) (1970) 2583–2593. https://doi.org/10.1021/bi00815a005.

[10]

J. J. Jr. Raia, J. A. Barone, W. G. Byerly, et al., Angiotensin-converting enzyme inhibitors: a comparative review, Ann. Pharmacother. 24(5) (1990) 506–525. https://doi.org/10.1177/106002809002400512.

[11]
V. Montinaro, M. Cicardi, ACE inhibitor-mediated angioedema. Int. Immunopharmacol. 78 (2020) 106081. https://doi.org/10.1016/j.intimp.2019.106081.
[12]
P. K. Whelton, R. M. Carey, W. S. Aronow, et al., ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood oressure in adults: a report of the American college of cardiology/American heart association task force on clinical practice guidelines, Circulation 138(17) (2018) e484–e594. https://doi.org/10.1161/HYP.0000000000000065.
[13]

R. Y. Yin, L. S. Yin, L. Li, et al., Hypertension in China: burdens, guidelines and policy responses: a state-of-the-art review, J. Hum. Hypertens. 36 (2022) 126–134. https://doi.org/10.1038/s41371-021-00570-z.

[14]
W. L. Wang, Z. Y. Cui, M. H. Ning, et al., In-silico investigation of umami peptides with receptor T1R1/T1R3 for the discovering potential targets: a combined modeling approach, Biomaterials 281 (2022) 121338. https://doi.org/10.1016/j.biomaterials.2021.121338.
[15]

F. Rivero-Pino, M. C. Millan-Linares, S. Montserrat-de-la-Paz, Strengths and limitations of in silico tools to assess physicochemical properties, bioactivity, and bioavailability of food-derived peptides, Trends Food Sci. Tech. 138 (2023) 433–440. https://doi.org/10.1016/j.jpgs.2023.06.023.

[16]

H. R. Ibrahim, A. S. Ahmed, T. Miyata, Novel angiotensin-converting enzyme inhibitory peptides from caseins and whey proteins of goat milk, J. Adv. Res. 8(1) (2017) 63–71. https://doi.org/10.1016/j.jare.2016.12.002.

[17]
Z. J. Du, J. Comer, Y. H. Li, Bioinformatics approaches to discovering food-derived bioactive peptides: reviews and perspectives, TrAC-Trend Anal. Chem. 162 (2023a) 117051. https://doi.org/10.1016/j.trac.2023.117051.
[18]
X. Y. Wang, J. Wang, Y. Lin, et al., QSAR study on angiotensin-converting enzyme inhibitor oligopeptides based on a novel set of sequence information descriptors. J. Mol. Model. 17(7) (2011) 1599–1606. https://doi.org/10.1007/s00894-010-0862-x.
[19]
R. Kumar, K. Chaudhary, M. Sharma, et al., AHTPDB: a comprehensive platform for analysis and presentation of antihypertensive peptides. Nucleic Acids Res. 43 (2015) D956–D962. https://doi.org/10.1093/nar/gku1141.
[20]
B. Manavalan, S. Basith, T. H. Shin, et al., mAHTPred: a sequence-based meta-predictor for improving the prediction of anti-hypertensive peptides using effective feature representation, Bioinformatics 35(16) (2019) 2757–2765. https://doi.org/10.1093/bioinformatics/bty1047.
[21]
Z. J. Du, X. J. Ding, Y. X. Xu, et al., UniDL4BioPep: a universal deep learning architecture for binary classification in peptide bioactivity, Brief. Bioinform. 24(3) (2023b) bbad135. https://doi.org/10.1093/bib/bbad135.
[22]

C. Ma, B. B. Ma, J. K. Li, et al., Changes in chemical composition and antioxidant activity of royal jelly produced at different floral periods during migratory beekeeping, Food Res. Int. 155 (2022) 111091. https://doi.org/10.1016/j.foodres.2022.111091.

[23]

A. Madani, B. Krause, E. R. Greene, et al., Large language models generate functional protein sequences across diverse families, Nat. Biotechnol. 41 (2023) 1099–1106. https://doi.org/10.1038/s41587-022-01618-2.

[24]

N. Brandes, D. Ofer, Y. Peleg, et al., ProteinBERT: a universal deep-learning model of protein sequence and function, Bioinformatics 38(8) (2022) 2102–2110. https://doi.org/10.1093/bioinformatics/btac020.

[25]
Z. Lin, H. Akin, R. Rao, et al., Evolutionary-scale prediction of atomic-level protein structure with a language model, Science 379(6637) (2023) 1123–1130. https://doi.org/10.1126/science.ade2574.
[26]

F. N. Yuan, Z. X. Zhang, Z. J. Fang, An effective CNN and transformer complementary network for medical image segmentation, Pattern Recognit. 136 (2023) 109228. https://doi.org/ 10.1016/j.patcog.2022.109228.

[27]

S. Ahmad, M. G. Campos, F. Fratini, et al., New insights into the biological and pharmaceutical properties of royal jelly, Int. J. Mol. Sci. 21(2) (2020) 382. https://doi.org/10.3390/ijms21020382.

[28]

F. Pan, X. X. Li, T. Tuersuntuoheti, et al., Molecular mechanism of high-pressure processing regulates the aggregation of major royal jelly proteins, Food Hydrocoll. 14 (2023) 108928. https://doi.org/10.1016/j.foodhyd.2023.108928.

[29]
S. Takaki-Doi, K. Hashimoto, M. Yamamura, et al., Antihypertensive activities of royal jelly protein hydrolysate and its fractions in spontaneously hypertensive rats, Acta Med. Okayama 63(1) (2009) 57–64. https://doi.org/0.18926/AMO/31859.
[30]
T. Matsui, A. Yukiyoshi, S. Doi, et al., Gastrointestinal enzyme production of bioactive peptides from royal jelly protein and their antihypertensive ability in SHR, J. Nutr. Biochem. 13(2) (2002) 80–86. https://doi.org/10.1016/S0955-2863(01)00198-X.
[31]
D. Probst, J. L. Reymond, Visualization of very large high-dimensional data sets as minimum spanning trees, J. Cheminformatics 12 (2020). https://doi.org/10.1186/s13321-020-0416-x.
[32]
M. Chimani, C. Gutwenger, M. Jünger, et al., The Open Graph Drawing Framework (OGDF). Chapter 17 in: R. Tamassia (ed.), Handbook of graph drawing and visualization, CRC Press, 2014, pp. 543–562. https://tcs.uos.de/_media/pubs/gdchapter_ogdf.pdf.
[33]
Q. Chen, C. Guestrin, XGBoost: a scalable tree boosting system, Kdd’16: proceedings of the 22nd ACM SIGKDD International Conference on Knowledge Discovery and Data Mining, 2016, pp. 785–794. https://doi.org/10.1145/2939672.2939785.
[34]

G. L. Ke, Q. Meng, T. Finley, et al., LightGBM: a highly efficient gradient boosting decision tree, Adv. Neural Inf. Process. Syst. 30 (2017) 3149–3157. https://doi.org/10.5555/3294996.3295074.

[35]
X. Glorot, A. Bordes, Y. Bengio, Deep sparse rectifier neural networks, in: International Conference on Artificial Intelligence and Statistics, 2011, pp. 315–323. https://api.semanticscholar.org/CorpusID:2239473.
[36]

N. K. Sinha, M. P. Griscik, A stochastic approximation method, IEEE Trans. Syst. Man Cybern. SMC-1(4) (1971) 338–344. https://doi.org/10.1109/TSMC.1971.4308316.

[37]

T. Lin, Y. Wang, X. Liu, et al., A survey of transformers, AI Open 3 (2022) 111–132. https://doi.org/10.1016/j.aiopen.2022.10.001.

[38]

J. Roslan, S. M. M. Kamal, K. F. M. Yunos, et al., Assessment on multilayer ultrafiltration membrane for fractionation of tilapia by-product protein hydrolysate with angiotensin I-converting enzyme (ACE) inhibitory activity, Sep. Purif. Technol. 173 (2017) 250–257. https://doi.org/10.1016/j.seppur.2016.09.038.

[39]

A. Mehmood, F. Pan, X. Ai, et al., Novel angiotensin-converting enzyme (ACE) inhibitory mechanism of peptides from Macadamia integrifolia antimicrobial protein 2 (MiAMP2), J. Food Biochem. 46(8) (2022) e14168. https://doi.org/10.1111/jfbc.14168.

[40]

O. Trott, A. J. Olson, AutoDock Vina: improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading, J. Comput. Chem. 31(2) (2010) 455–461. https://doi.org/10.1002/jcc.21334.

[41]

R. Kumar, K. Chaudhary, J. Singh Chauhan, et al., An in silico platform for predicting, screening and designing of antihypertensive peptides, Sci. Rep. 5 (2015) 12512. https://doi.org/ 10.1038/srep12512.

[42]
L. Wang, N. Wang, W. Zhang, et al., Therapeutic peptides: current applications and future directions, Signal Transduction Targeted Ther, 7 (2022) 48. https://doi.org/10.1038/s41392-022-00904-4.
[43]

J. Wu, R. E. Aluko, S. Nakai, Structural requirements of angiotensin I-converting enzyme inhibitory peptides: quantitative structure-activity relationship study of di- and tripeptides, J. Agric. Food. Chem. 54(3) (2006) 732–738. https://doi.org/10.1021/jf051263l.

[44]

Z. Q. He, G. Liu, Z. J. Qiao, et al., Novel angiotensin-I converting enzyme inhibitory peptides isolated from rice wine lees: purification, characterization, and structure-activity relationship, Front. Nutr. 8 (2021) 746113. https://doi.org/10.3389/fnut.2021.746113.

[45]

C. Daskaya-Dikmen, A. Yucetepe, F. Karbancioglu-Guler, et al., Angiotensin-I-converting enzyme (ACE)-inhibitory peptides from plants, Nutrients 9(4) (2017) 316. https://doi.org/10.3390/nu9040316.

[46]

S. Manoharan, A. S. Shuib, N. Abdullah, Structural characteristics and antihypertensive effects of angiotensin-I-converting enzyme inhibitory peptides in the renin-angiotensin and kallikrein kinin systems, Afr. J. Tradit. Complem. 14(2) (2017) 383–406. https://doi.org/10.21010/ajtcam.v14i2.39.

[47]
C. Beeton, Targets and therapeutic properties, in: Abba J. Kastin (Eds.), Handbook of biologically active peptides (Second edition), Academic Press, 2013, pp. 473–482. https://doi.org/10.1016/B978-0-12-385095-9.00064-6.
[48]
J. Chen, H. H. Cheong, S. W. I. Siu, xDeep-AcPEP: deep learning method for anticancer peptide activity prediction based on convolutional neural network and multitask learning, J. Chem. Inf. Model. 61(8) (2021) 3789–3803. https://doi.org/10.1021/acs.jcim.1c00181.
[49]
Z. J. Du, X. J. Ding, W. Hsu, et al., pLM4ACE: a protein language model based predictor for antihypertensive peptide screening, Food Chem. 431 (2024) 137162. https://doi.org/10.1016/j.foodchem.2023.137162.
[50]

Y. Ma, Z. Y. B. Guo, B. Xia, et al., Identification of antimicrobial peptides from the human gut microbiome using deep learning, Nature Biotechnol. 40 (2022) 921–931. https://doi.org/10.1038/s41587-022-01226-0.

Food Science of Animal Products
Article number: 9240053
Cite this article:
Pan F, Liu D, Tuersuntuoheti T, et al. Mining anti-hypertensive peptides in animal food through deep learning: a case study of gastrointestinal digestive products of royal jelly. Food Science of Animal Products, 2024, 2(1): 9240053. https://doi.org/10.26599/FSAP.2024.9240053

1063

Views

197

Downloads

1

Crossref

Altmetrics

Received: 26 March 2024
Revised: 19 April 2024
Accepted: 25 April 2024
Published: 17 May 2024
© Beijing Academy of Food Sciences 2024.

Food Science of Animal Products published by Tsinghua University Press. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

Return