From Observation to Mechanistic Insight: Image-based Systems Biology of Human Pathogenic Fungi

WHO. WHO fungal priority pathogens list to guide research, development and public health action. World Health Organization, 2022. Accessed 2 Feb 2026. https://www.who.int/publications/i/item/9789240060241

Mendonça A, Santos H, Franco-Duarte R, Sampaio P. Fungal infections diagnosis - past, present and future. Res Microbiol. 2022;173(3):103915. https://doi.org/10.1016/j.resmic.2021.103915.

Article  CAS  PubMed  Google Scholar 

Thambugala KM, Daranagama DA, Tennakoon DS, Jayatunga DPW, Hongsanan S, Xie N. Humans vs. fungi: an overview of fungal pathogens against humans. Pathogens. 2024;13(5):426. https://doi.org/10.3390/pathogens13050426.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brown GD, Ballou ER, Bates S, Elaine M, Bignell EM, Borman AM, et al. The pathobiology of human fungal infections. Nat Rev Microbiol. 2024;22:687–704. https://doi.org/10.1038/s41579-024-01062-w.

Article  CAS  PubMed  Google Scholar 

Janbon G, Quintin J, Lanternier F, d’Enfert C. Studying fungal pathogens of humans and fungal infections: fungal diversity and diversity of approaches. Genes Immun. 2019;20(5):403–14. https://doi.org/10.1038/s41435-019-0071-2.

Article  PubMed  Google Scholar 

Fisher MC, Alastruey-Izquierdo A, Berman J, Bicanic T, Bignell EM, Bowyer P, et al. Tackling the emerging threat of antifungal resistance to human health. Nat Rev Microbiol. 2022;20:557–71. https://doi.org/10.1038/s41579-022-00720-1.

Article  CAS  PubMed  PubMed Central  Google Scholar 

van Rhijn N, Arikan-Akdagli S, Beardsley J, Bongomin F, Chakrabarti A, Chen SC, et al. Beyond bacteria: the growing threat of antifungal resistance. Lancet. 2024;404(10457):1017–8. https://doi.org/10.1016/S0140-6736(24)01695-7.

Article  PubMed  Google Scholar 

Medyukhina A, Timme S, Mohtari Z, Figge MT. Image-based systems biology of infection. Cytometry A. 2015;87(6):462–70. https://doi.org/10.1002/cyto.a.22638.

Article  PubMed  Google Scholar 

Ewald J, Rivieccio F, Radosa L, Schuster S, Brakhage AA, Kaleta C. Dynamic optimization reveals alveolar epithelial cells as key mediators of host defense in invasive aspergillosis. PLoS Comput Biol. 2021;17(12):e1009645. https://doi.org/10.1371/journal.pcbi.1009645.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Saffer C, Timme S, Ortiz SC, Bertuzzi M, Figge MT. Spatiotemporal modeling quantifies cellular contributions to uptake of Aspergillusfumigatus in the human lung. Commun Biol. 2024;7:1615. https://doi.org/10.1038/s42003-024-07302-2.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lehnert T, Prauße MTE, Hünniger K, Praetorius J-P, Kurzai O, Figge MT. Comparative assessment of immune evasion mechanisms in human whole-blood infection assays by a systems biology approach. PLoS ONE. 2021;16(4):e0249372. https://doi.org/10.1371/journal.pone.0249372.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Lehnert T, Leonhardt I, Timme S, Thomas-Rüddel D, Bloos F, Sponholz S, et al. Ex vivo immune profiling in patient blood enables quantification of innate immune effector functions. Sci Rep. 2021;11:12039. https://doi.org/10.1038/s41598-021-91362-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Brodland GW. How computational models can help unlock biological systems. Semin Cell Dev Biol. 2015;47:62–73. https://doi.org/10.1016/j.semcdb.2015.07.001.

Article  PubMed  Google Scholar 

Hünniger K, Lehnert T, Bieber K, Martin R, Figge MT, Kurzai O. A virtual infection model quantifies innate effector mechanisms and Candidaalbicans immune escape in human blood. PLoS Comput Biol. 2014;10(2):e1003479. https://doi.org/10.1371/journal.pcbi.1003479.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Meyer-Hermann M, Figge MT, Straub RH. Mathematical modeling of the circadian rhythm of key neuroendocrine-immune system players in rheumatoid arthritis: a systems biology approach. Arthritis Rheum. 2009;60(9):2585–94. https://doi.org/10.1002/art.24797.

Article  PubMed  Google Scholar 

Stringer C, Pachitariu M. Cellpose3: one-click image restoration for improved cellular segmentation. Nat Methods. 2025;22:592–9. https://doi.org/10.1038/s41592-025-02595-5.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Cutler KJ, Stringer C, Lo TW, et al. Omnipose: a high-precision morphology-independent solution for bacterial cell segmentation. Nat Methods. 2022;19:1438–48. https://doi.org/10.1038/s41592-022-01639-4.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Ershov D, Phan MS, Pylvänäinen JW, et al. Trackmate 7: integrating state-of-the-art segmentation algorithms into tracking pipelines. Nat Methods. 2022;19:829–32. https://doi.org/10.1038/s41592-022-01507-1.

Article  CAS  PubMed  Google Scholar 

Schindelin J, Arganda-Carreras I, Frise E, et al. Fiji: an open-source platform for biological-image analysis. Nat Methods. 2012;9:676–82. https://doi.org/10.1038/nmeth.2019.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schneider C, Rasband W, Eliceiri K. NIH image to ImageJ: 25 years of image analysis. Nat Methods. 2012;9:671–5. https://doi.org/10.1038/nmeth.2089.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Berg S, Kutra D, Kroeger T, et al. Ilastik: interactive machine learning for (bio)image analysis. Nat Methods. 2019;16:1226–32. https://doi.org/10.1038/s41592-019-0582-9.

Article  CAS  PubMed  Google Scholar 

Ren R, Tan W, Chen S, et al. Deep learning application to hyphae and spores identification in fungal fluorescence images. Sci Rep. 2025;15:27222. https://doi.org/10.1038/s41598-025-11228-y.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Praetorius J-P, Hitzler SUJ, Gresnigt M, Figge MT. Image-based quantification of Candida albicans filamentation and hyphal length using the open-source visual programming language JIPipe. FEMS Yeast Res. 2025. https://doi.org/10.1093/femsyr/foaf011.

Article  PubMed  PubMed Central  Google Scholar 

Gerst R, Cseresnyés Z, Figge MT. JIPipe: visual batch processing for ImageJ. Nat Methods. 2023;20:168–9. https://doi.org/10.1038/s41592-022-01744-4.

Article  CAS  PubMed  Google Scholar 

Oyarte Galvez L, Bisot C, Bourrianne P, et al. A travelling-wave strategy for plant–fungal trade. Nature. 2025;639:172–80. https://doi.org/10.1038/s41586-025-08614-x.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Kaden T, Alonso-Roman R, Akbarimoghaddam P, Mosig AS, Graf K, Raasch M, et al. Modeling of intravenous caspofungin administration using an intestine-on-chip reveals altered Candidaalbicans microcolonies and pathogenicity. Biomaterials. 2024;307:122525. https://doi.org/10.1016/j.biomaterials.2024.122525.

Article  CAS  PubMed  Google Scholar 

Olivier FAB, Hilsenstein V, Weerasinghe H, Weir A, Hughes S, Crawford S, et al. The escape of Candidaalbicans from macrophages is enabled by the fungal toxin candidalysin and two host cell death pathways. Cell Rep. 2022;40(12):111374. https://doi.org/10.1016/j.celrep.2022.111374.

Article  CAS  PubMed  Google Scholar 

Bansal L, Nichols E-M, Howsmon DP, Neisen J, Bessant CM, Cunningham F, et al. Mathematical modeling of complement pathway dynamics for target validation and selection of drug modalities for complement therapies. Front Pharmacol. 2022;13:855743.

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