Preview

Journal of NBC Protection Corps

Advanced search

New Methods for Pathogen Risk Assessment: Machine Learning in the Analysis of Toxicity Spectrum of Albifimbria verrucaria

https://doi.org/10.35825/2587-5728-2025-9-1-57-73

EDN: aysnnq

Abstract

Highlights

The use of artificial intelligence has great potential for predicting the toxic properties of new little-studied chemical compounds, reducing the time and financial costs associated with identifying the risks of possible threats.

Relevance. Mycotoxins, which are secondary metabolites of mold fungi, represent one of the most significant factors of chronic risk associated with food products. Their danger exceeds the threat posed by synthetic pollutants, plant toxins, food additives, and pesticide residues. However, for many mycotoxins, the full toxicological profile has not yet been established, and traditional analysis methods remain labor-intensive, costly, and insufficiently effective. This makes the search for new approaches to assess their danger and control highly relevant.

Purpose of the study is to study the toxicological profile of mycotoxins produced by the pathogenic fungus Albifimbria verrucaria and to determine their level of danger using chemoinformatics and machine learning.

Study base sources. Analysis of scientific literature available through open Russian and English-language Internet resources.

Method. In silico methods were applied to analyze the toxicological profile of mycotoxins, enabling the identification of high-risk compounds. These methods prioritize substances for further in-depth toxicological assessment, significantly reducing the time and resources required for research.

Results and Discussion. The study results showed that approximately 50% of mycotoxins produced by mold fungi belong to hazard classes I and II. At the same time, a significant portion of these compounds remains outside the control zone, despite their potential threat to living organisms. This highlights the need for more thorough study and monitoring of such substances.

Conclusions. The obtained data confirm the importance of developing and implementing modern systems for monitoring and regulating mycotoxins, especially for poorly studied and new compounds. The use of chemoinformatic methods makes it possible to effectively identify the most hazardous substances and focus efforts on their research, thereby enhancing food safety and reducing risks to human and animal health.

About the Authors

V. T. Tkachenko
A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences
Russian Federation

Varvara T. Tkachenko. Postgraduate. 

Bolshoy Karetny per., 19, bld 1, 127051 Moscow 



M. V. Fedorov
A.A. Kharkevich Institute for Information Transmission Problems, Russian Academy of Sciences ; Skolkovo Institute of Science and Technology
Russian Federation

Maxim V. Fedorov. Acting Director. Cand. Sci. (Phys-Math.). Dr Sci. (Chem.). Corresponding Member, Russian Academy of Sciences. 

Bolshoy Karetny per., 19, bld 1, 127051 Moscow 

121205 Moscow 



V. V. Fedorova
Skolkovo Institute of Science and Technology
Russian Federation

Victoria V. Fedorova. Researcher. Cand. Sci. (Biol.). 

Bolshoy Boulevard, 30, bld. 1, Moscow 121205



A. V. Pozdeev
Nuclear Biological Chemical Defence Military Academy Named after Marshal of the Soviet Union S.K. Timoshenko (Kostroma) of the Ministry of Defence of the Russian Federation
Russian Federation

Aleksandr V. Pozdeev. Professor. Dr Sci. (Biol.). 

Gorky Street 16, Kostroma 156015 



E. B. Kormanovskaya
Nuclear Biological Chemical Defence Military Academy Named after Marshal of the Soviet Union S.K. Timoshenko (Kostroma) of the Ministry of Defence of the Russian Federation
Russian Federation

Elena B. Kormanovskaya. Senior Researcher. Cand. Sci. (Biol.). Assistant Professor. 

Gorky Street 16, Kostroma 156015 



A. S. Klimova
Nuclear Biological Chemical Defence Military Academy Named after Marshal of the Soviet Union S.K. Timoshenko (Kostroma) of the Ministry of Defence of the Russian Federation
Russian Federation

Alena S. Klimova. Junior Researcher

Gorkogo Street, 16, Kostroma 156015 



P. V. Gunina
Nuclear Biological Chemical Defence Military Academy Named after Marshal of the Soviet Union S.K. Timoshenko (Kostroma) of the Ministry of Defence of the Russian Federation
Russian Federation

Polina V. Gunina. Junior Researcher 

Gorky Street 16, Kostroma 156015 



References

1. Restrepo G. Chemical space: limits, evolution and modelling of an object bigger than our universal library. Digital Discovery. 2022;1(5):568–85. EDN:GZRUYT https://doi.org/10.1039/D2DD00030J

2. Leal W, Llanos Eugenio J, Bernal A, Restrepo G. The expansion of chemical space in 1826 and in the 1840s prompted the convergence to the periodic system. Proceedings of the National Academy of Sciences. 2022;119(30):e2119083119. EDN:NGKLID. https://doi.org/10.1073/pnas.2119083119

3. Schummer J. Scientometric studies on chemistry I: The exponential growth of chemical substances, 1800– 1995. Scientometrics. 1997;39:107–23. EDN:DUSMND. https://doi.org/10.1007/bf02457433

4. Drew KLM, Baiman H, Khwaounjoo P, Yu B, Reynisson J. Size estimation of chemical space: how big is it? Journal of Pharmacy and Pharmacology. 2012;64(4):490–5. https://doi.org/10.1111/j.2042-7158.2011.01424.x

5. Medina Á., González-Jartín J.M., Sainz M.J. Impact of global warming on mycotoxins. Current Opinion in Food Science. 2017;18:76–81. https://doi.org/10.1016/j.cofs.2017.11.009

6. Alberga D, Trisciuzzi D, Kamel M, Mangiatordi G, Nicolotti O. Prediction of acute oral systemic toxicity using a multifingerprint similarity approach. Toxicological Sciences. 2019;167(2):484–95. EDN: ONWHZE. https://doi.org/10.1093/toxsci/kfy255

7. Moretti A, Logrieco AF, Susca A. Mycotoxins: An underhand food problem. Mycotoxigenic Fungi: Methods and Protocols. 2017;1542:3–12. https://doi.org/10.1007/978-1-4939-6707-0_1

8. El-Sayed R, Jebur A, Kang W, El-Esawi M, El-Demerdash F. An overview on the major mycotoxins in food products: Characteristics, toxicity, and analysis. Journal of Future Foods. 2022;2(2):91–102. EDN:AISVGN. https://doi.org/10.1016/j.jfutfo.2022.03.002

9. Tolosa J, Candelas E, Pardo J, Goya A, Moncho Escriva S, Rafael G, et al. MicotoXilico: an interactive database to Predict Mutagenicity, Genotoxicity, and carcinogenicity of mycotoxins. Toxins. 2023;15(6):355. EDN:AIPOEV. https://doi.org/10.3390/toxins15060355

10. Baute MA, Deffieux G, Baute R, Neveu A. New antibiotics from the fungus Epicoccum nigrum. I. Fermentation, isolation and antibacterial properties. Journal of Antibiotics. 1978;31(11):1099–101. https://doi.org/10.7164/antibiotics.31.1099

11. Wang Yu, Guo L-D, Hyde K. Taxonomic placement of sterile morphotypes of endophytic fungi from Pinus tabulaeformis (Pinaceae) in northeast China based on rDNA sequences. Fungal Diversity. 2005;20:235–60.

12. Brooks FT. Notes on the pathogenicity of Myrothecium roridum tode ex fr. Transactions of the British Mycological Society. 1945;27(3-4):155–7.

13. Domsh КН, Gams W, Anderson T-H. Compendium of Soil Fungi. 2nd ed., taxonomically revised by Walter Gams. Germany: IHW-Verlag; 2007. 672 р.

14. Quezado Duval AM, Henz GP, Paz-Lima ML, Medeiros AR, Miranda BEC, Pfenning LH, et al. New hosts of Myrothecium SPP. In Brazil and a preliminary In Vitro assay of fungicides. Braz J Microbiol. 2010;41(1):246–52. https://doi.org/10.1590/S1517-83822010000100034

15. Cunfer BM. Studies on the biology of Myrothecium roridum and M. verrucaria pathogenic on red clover. Phytopathology. 1969;59:1306–9.

16. Ellis MB, Ellis Pamela J. Microfungi on Land Plants: An Identification Handbook. New York: Macmillan; 1985. 818 p.

17. Watanabe T. Illustrated atlas of soil and seed fungi. USA, Florida: CRC Press; 1993. 426 р.

18. Ahrazem O, Gómez-Miranda B, Prieto A, Bernabé M, Leal J. Heterogeneity of the genus Myrothecium as revealed by cell wall polysacharides. Archives of Microbiology. 2000;173(4):296–302. EDN:AVBTEJ. https://doi.org/10.1007/s002030000149

19. Anderson KI. Herbicidal spectrum and activity of Myrothecium verrucaria. Weed Science. 2009;52(4):623–7. https://doi.org/10.1614/WS-03-101R1

20. Seifert KA, Gams W. The genera of Hyphomycetes-2011 update. Persoonia. 2011;27:119–29. EDN:KQXQEP. https://doi.org/10.3767/003158511X617435

21. Yuan-Hsun H, Akira H, Shoji S, Masahira N, Hiroshi N, Toshiji T, et al. Structure of Myrocin C, a New Diterpene Antibiotic Produced by a Strain of Myrothecium sp. Agricultural and Biological Chemistry. 1987;51(12):3455–7. https://doi.org/10.1080/00021369.1987.10868553

22. Hoagland RE, Weaver MA, Boyette CD. Myrothecium verrucariu fungus; A bioherbicide and strategies to reduce its non-target risks. Allelopathy J. 2007;19(1):179–92.

23. Bräse S, Encinas A, Keck J, Nising CF. Chemistry and biology of mycotoxins and related fungal metabolites. Chem Rev. 2009;109(9):3903–90. EDN:MYWLGT. https://doi.org/10.1021/cr050001f

24. Zou X, Niu S, Ren J, Li E, Liu X, Che Y. Verrucamides A–D, antibacterial cyclopeptides from Myrothecium verrucaria. J Nat Prod. 2011;74(5):1111–6. https://doi.org/10.1021/np200050r

25. Basnet BB, Liu L, Chen B, Suleimen YM, Yu H, Guo S, et al. Four New Cytotoxic Arborinane-Type Triterpenes from the Endolichenic Fungus Myrothecium inundatum. Planta Med. 2019;85(9–10):701–7. EDN:XRYDMH. https://doi.org/10.1055/a-0855-4051

26. Ueno Y. Trichothecenes: Chemical, Biological, and Toxicological Aspects (Developments in Food Science). Tokyo: Elsevier Science Ltd; 1983. 313 p.

27. Moss MO. Mycotoxins. Mycol Res; 1996:100:513–23.

28. Wagenaar MM, Clardy J. Two new roridins isolated from Myrothecium sp. J Antibiot. 2001;54(6):517. https://doi.org/10.7164/antibiotics.54.517

29. Kobayashi H, Namikoshi M, Yoshimoto T, Yokochi T. A screening method for antimitotic and antifungal substances using conidia of Pyricularia oryzae, modification and application to tropical marine fungi. J Antibiot. 1996;49(9):873–9. https://doi.org/10.7164/antibiotics.49.873

30. Pervez MR, Musaddiq M, Thakare PV In vitro antimicrobial studies of isolated Myrothecium spp mrp001 against human pathogens. International Journal of Basic and Applied Medical Sciences. 2012;2(3):228–36.

31. Ruma K, Sunil K, Prakash HS. Bioactive potential of endophytic Myrothecium sp. isolate M1-CA-102, associated with Calophyllum apetalum. Pharmaceutical Biology. 2014;52(6):665–76. https://doi.org/10.3109/13880209.2013.863950

32. Fu Y, Wu P, Jinghua X, Wei X. Cytotoxic and Antibacterial Quinone Sesquiterpenes from a Myrothecium Fungus. Journal of Natural Products. 2014;77(8):1791–9. https://doi.org/10.1021/np500142g

33. Chen Y, Ran SF, Dai D-Q, Wang Y, Hyde KD, Wu YM, et al. Mycosphere Essays 2. Myrothecium. Mycosphere. 2016;7:64–80. EDN:WQFCXL. https://doi.org/10.5943/mycosphere/7/1/7

34. Nguyen LT, Jang JY, Kim TY, Yu NH, Park AR, Lee S, et al. Nematicidal activity of verrucarin A and roridin A isolated from Myrothecium verrucaria against Meloidogyne incognita. Pesticide Biochemistry and Physiology. 2018;148:133–43. https://doi.org/10.1016/j.pestbp.2018.04.012

35. Mondol MA, Surovy MZ, Islam MT, Schüffler A, Laatsch H. Macrocyclic trichothecenes from Myrothecium roridum strain M10 with motility inhibitory and zoosporicidal activities against Phytophthora nicoti nae. Journal of Agricultural and Food Chemistry. 2015;63(40):8777–86. EDN:VESBPP. https://doi.org/10.1021/acs.jafc.5b02366

36. Carter K, Rameshwar P, Ratajczak MZ, Kakar SS. Verrucarin J inhibits ovarian cancer and targets cancer stem cells. Oncotarget. 2017;8(54):92743. https://doi.org/10.18632/oncotarget.21574

37. Nakagawa M, Hsu YH, Hirota A, Shima S, Nakayama M. Myrocin C, a new diterpene antitumor antibiotic from Myrothecium verrucaria. J Antibiot. 1989;42(2):218–22. https://doi.org/10.7164/antibiotics.42.218

38. Murakami R, Kobayashi T, Takahashi K. Myrothecium leaf spot of mulberry caused by Myrothecium verrucaria. Journal of General Plant Pathology. 2005;71(2):153–5. https://doi.org/10.1007/s10327-004-0178-8

39. Ye W, Chen Y, Li H, Zhang W, Liu H, Sun Z, et al. Two trichothecene mycotoxins from Myrothecium roridum induce apoptosis of HepG-2 cells via caspase activation and disruption of mitochondrial membrane potential. Molecules. 2016;21(6):781. https://doi.org/10.3390/molecules21060781

40. Boyette CD, Weaver MA, Hoagland RE, Stetina KC. Submerged culture of a mycelial formulation of a bioherbicidal strain of Myrothecium verrucaria with mitigated mycotoxin production. World Journal of Microbiology and Biotechnology. 2008;24(11):2721–6. https://doi.org/10.1007/s11274-008-9759-6

41. Shimizu A, Kwon JH, Sasaki T, Satoh T, Sakurai N, Sakurai T, et al. Myrothecium verrucaria bilirubin oxidase and its mutants for potential copper ligands. Biochemistry. 1999;9;38(10):3034–42. https://doi.org/10.1021/bi9819531

42. Sulistyaningdyah WT, Ogawa J, Tanaka H, Maeda C, Shimizu S. Characterization of alkaliphilic laccase activity in the culture supernatant of Myrothecium verrucaria 24G-4 in comparison with bilirubin oxidase. FEMS Microbiology Letters. 2004;230:209–14. https://doi.org/10.1016/S0378-1097(03)00892-9

43. Han X, Zhao M, Lu L, Liu Y. Purification, characterization and decolorization of bilirubin oxidase from Myrothecium verrucaria 3.2190. Fungal Biol. 2012;116(8):863–71. https://doi.org/10.1016/j.funbio.2012.05.003

44. Zhang X, Liu Y, Yan K, Wu H. Decolorization of anthraquinone-type dye by bilirubin oxidase-producing nonligninolytic fungus Myrothecium sp. IMER1. J Biosci Bioeng. 2007;104(2):104–10. https://doi.org/10.1263/jbb.104.104

45. Mano N. Features and applications of bilirubin oxidases. Applied Microbiology and Biotechnology. 2012;96(2):301–7. EDN:RHYOTX. https://doi.org/10.1007/s00253-012-4312-9

46. Pita M, Gutierrez-Sanchez C, Toscano MD, Shleev S, De Lacey A. Oxygen biosensor based on bilirubin oxidase immobilized on a nanostructured gold electrode. Bio Electrochemistry. 2013;94:69–74. EDN:RHYPNX. https://doi.org/10.1016/j.bioelechem.2013.07.001

47. Khovpachev AA, Basharin VA, Chepur SV, Tsoi DV, Ivanov IM, Volobuev SV, et al. Modern concepts of toxins of higher fungi: nitrogen-free organic compounds. Successes in modern Biology. 2022;142(1):37–51 (in Russian). EDN:KWQUYZ. https://doi.org/10.31857//S0042132421050045

48. Mahato DK, Pandhi S, Kamle M, Gupta A, Sharma B, Panda BK, et al. Trichothecenes in food and feed: Occurrence, impact on human health and their detection and management strategies. Toxicon. 2022;208:62–77. EDN:QSMZAY. https://doi.org/10.1016/j.toxicon.2022.01.011

49. Franklin R-C, Mizael M, Juan FM. Micheloud Plants causing poisoning outbreaks of livestock in South America: A review. Toxicon: X. 2023;17:100–50. EDN:GQAEAT. https://doi.org/10.1016/j.toxcx.2023.100150

50. Raslan M, Raslan S, Shehata E, Mahmoud A, Ali Sabri N. Advances in the applications of bioinformatics and chemoinformatics. Pharmaceuticals. 2023;16(7):1050. EDN:YITQPD. https://doi.org/10.3390/ph16071050

51. Kar S, Leszczynski J. Open access in silico tools to predict the ADMET profiling of drug candidates. Expert Opinion on Drug Discovery. 2020;15(12):1473–87. EDN:RUWRPT. https://doi.org/10.1080/17460441.2020.1798926

52. Roy K, Kar S, Das RN. Understanding the basics of QSAR for applications in pharmaceutical sciences and risk assessment. Academic Press; 2015. P. 151–89. EDN:VFCJVV. https://doi.org/10.1016/b978-0-12-801505-6.00005-3

53. Khamidulina KhKh, Tarasova EV, Lastovetsky ML. Prediction of the biodegradation of chemicals using OECD QSAR Toolbox software. Toxicological Review. 2024;32(1):20–30 (in Russian). EDN:LCYWKX. https://doi.org/10.47470/0869-7922-2024-32-1-20-30

54. Khamidulina KhKh, Tarasova EV, Lastovetskiy ML. Application of the OECD QSAR Toolbox software for calculating the parameters of acute aquatic toxicity of chemicals. Toxicological Review. 2022;30(1):45–54 (in Russian). EDN:XBJLBR. https://doi.org/10.47470/0869-7922-2022-30-1-45-54

55. Prüss-Ustün A, Wolf J, Corvalan C, Bos R, Neira M. Preventing disease through healthy environments: a global assessment of the burden of disease from environmental risks. World Health Organization. 2016:241–54.

56. Bondar D, Kapitanov I, Pulkrábková L, Soukup O, Jun D, Diniz FB, et al. N-substituted arylhydroxamic acids as acetylcholinesterase reactivators. Chemico-Biological Interactions. 2022;365:110078. EDN:IIAYJR. https://doi.org/10.1016/j.cbi.2022.110078

57. Puthongkham P, Wirojsaengthong S, Suea-Ngam A. Machine learning and chemometrics for electrochemical sensors: moving forward to the future of analytical chemistry. Analyst. 2021;146(21):6351–64. EDN:MIZDMQ. https://doi.org/10.1039/d1an01148k

58. Sharov SA, Batinov DS, Osipov MA, Domnin MV, Morozov SA, Golyshev MA, et al. Justification of the Architecture a Promising Automated System for Monitoring Radiation, Chemical and Biological Environment Using Artificial Intelligence. Journal of NBC Protection Corps. 2024;8(1):65–77 (in Russian). EDN:ZYEOUX. https://doi.org/10.35825/2587-5728-2024-8-1-65-77

59. Shkil D, Muhamedzhanova A, Petrov Ph, Skorb E, Aliev T, Steshin IS, et al. Expanding Predictive Capacities in Toxicology: Insights from Hackathon-Enhanced Data and Model Aggregation. Molecules. 2024;29(8):1826. EDN:EDHGMQ. https://doi.org/10.3390/molecules29081826

60. Sosnin S, Karlov D, Tetko IV, Fedorov MV. Comparative Study of Multitask Toxicity Modeling on a Broad Chemical Space. Journal of Chemical Information and Modeling. 2019;59(3):1062–72. EDN:UXBSKF. https://doi.org/10.1021/acs.jcim.8b00685

61. Sosnin S, Misin M, Palmer DS, Fedorov MV. 3D matters! 3D-RISM and 3D convolutional neural network for accurate bioaccumulation prediction. Journal of Physics: Condensed Matter. 2018;30(32):32LT03. EDN:YBXXZR. https://doi.org/10.1088/1361-648X/aad076

62. Andronov M, Fedorov MV, Sosnin S. Exploring Chemical Reaction Space with Reaction Difference Fingerprints and Parametric t-SNE. ACS Omega. 2021;6(45):30743–51. EDN:VBFOTO. https://doi.org/10.1021/acsomega.1c04778

63. Krasnov L, Khokhlov I, Fedorov MV, Sosnin S. Transformer-based artificial neural networks for the conversion between chemical notations. Scientific Reports. 2021;11(1):14798. EDN:SSGGTK. https://doi.org/10.1038/s41598-021-94082-y

64. Sosnina EA, Sosnin S, Nikitina AA, Nazarov I, Osolodkin DI, Fedorov MV. Recommender systems in antiviral drug discovery. ACS Omega. 2020;5(25):15039–51. EDN:UTFTWS. https://doi.org/10.1021/acsomega.0c00857

65. Efremenko EN, Lyagin IV. The problem of mycotoxins and approaches to its solution. Journal of NBC Protection Corps. 2024;8(4):356–67 (in Russian). EDN:BLXMFC. https://doi.org/10.35825/2587-5728-2024-8-4-356-367

66. Şcerbacova T. Trichoderma fungi for plant protection from Albifimbria verrucaria (Myrothecium). Biotehnologii avansate-realizari §i perspective. 2022;6:226–8. https://doi.org/10.53040/abap6.2022.76

67. Amagata T, Rath C, Rigot JF, Tarlov N, Tenney K, Valeriote FA, et al. Structures and Cytotoxic Properties of Trichoverroids and Their Macrolide Analogues Produced by Saltwater Culture of Myrothecium verrucaria. Journal of Medicinal Chemistry. 2003;46(20):4342–50. https://doi.org/10.1021/jm030090t

68. Parvatkar PT, Maher SP, Zhao Y, Cooper CA, de Castro ST, Peneau J, et al. In Vitro Antimalarial Activity of Trichothecenes against Liver and Blood Stages of Plasmodium Species. Journal of Natural Products. 2024;87(2):315–21. EDN:NNFEOQ. https://doi.org/10.1021/acs.jnatprod.3c01019

69. Ulrich S, Gottschalk C, Biermaier B, Bahlinger E, Twaruzek M, Asmussen S, et al. Occurrence of type A, B and D trichothecenes, zearalenone and stachybotrylactam in straw. Archives of Animal Nutrition. 2021;75(2):105–20. EDN:IROYES. https://doi.org/10.1080/1745039X.2021.1877075

70. Chang PK, Ehrlich KC, Fujii I. Cyclopiazonic acid biosynthesis of Aspergillus flavus and Aspergillus oryzae. Toxins. 2009;1(2):74–99. https://doi.org/10.3390/toxins1020074

71. Whitaker TB. Sampling foods for mycotoxins. Food additives and contaminants. 2006;23(1):50–61. https://doi.org/10.1080/02652030500241587

72. Whitaker TB, Dickens JW, Monroe RJ. Comparison of the observed distribution of aflatoxin in shelled peanuts to the negative binomial distribution. Journal of the American Oil Chemists' Society. 1972;49(10):590–3. https://doi.org/10.1007/BF02609233


Review

For citations:


Tkachenko V.T., Fedorov M.V., Fedorova V.V., Pozdeev A.V., Kormanovskaya E.B., Klimova A.S., Gunina P.V. New Methods for Pathogen Risk Assessment: Machine Learning in the Analysis of Toxicity Spectrum of Albifimbria verrucaria. Journal of NBC Protection Corps. 2025;9(1):57-73. (In Russ.) https://doi.org/10.35825/2587-5728-2025-9-1-57-73. EDN: aysnnq

Views: 133


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2587-5728 (Print)
ISSN 3034-2791 (Online)