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2025
Guerrero-Navarro, Lena; Monfort-Lanzas, Pablo; Krichbaumer, Vinzenz; AraĂșjo, Mariana E. G. De; Monfregola, Jlenia; Huber, Lukas A.; Ballabio, Andrea; Jansen-DĂŒrr, Pidder; Cavinato, Maria
TFEB Orchestrates Stress Recovery and Paves the Way for Senescence Induction in Human Dermal Fibroblasts ArtĂculo de revista
En: Aging Cell, vol. 24, no 7, pp. e70083, 2025, ISSN: 1474-9726.
@article{guerrero-navarro_tfeb_2025,
title = {TFEB Orchestrates Stress Recovery and Paves the Way for Senescence Induction in Human Dermal Fibroblasts},
author = {Lena Guerrero-Navarro and Pablo Monfort-Lanzas and Vinzenz Krichbaumer and Mariana E. G. De AraĂșjo and Jlenia Monfregola and Lukas A. Huber and Andrea Ballabio and Pidder Jansen-DĂŒrr and Maria Cavinato},
doi = {10.1111/acel.70083},
issn = {1474-9726},
year = {2025},
date = {2025-07-01},
journal = {Aging Cell},
volume = {24},
number = {7},
pages = {e70083},
abstract = {Cells experience oxidative stress and widespread cellular damage during stress-induced premature senescence (SIPS). Senescent cells show an increase in lysosomal content, which may contribute to mitigating cellular damage by promoting autophagy. This study investigates the dynamics of lysosomal quality control in human dermal fibroblasts (HDF), specifically examining lysosomal signaling pathways during oxidative stress-induced SIPS. Our results reveal distinct signaling responses between the initial stress phase and the ensuing senescent phenotype. During the stress phase, treatment with tBHP, which undermines the antioxidant response, leads to elevated reactive oxygen species (ROS) and lysosomal damage. ROS accumulation activates AMP-activated protein kinase (AMPK) and inhibits Akt, which correlates with the suppression of mammalian target of rapamycin (mTOR). Inactivation of mTOR during this phase aligns with the activation of transcription factor EB (TFEB), a key regulator of autophagy and lysosomal biogenesis. TFEB knockdown under stress increased apoptosis, highlighting the protective role of TFEB in the stress response. As cells transition to senescence, TFEB activity, required for the autophagic damage repair, becomes less critical. The decrease in ROS levels leads to the normalization of AMPK and Akt signaling, accompanied by the reactivation of mTOR. This reactivation of mTOR, which is critical for establishing the senescent state, is observed alongside the inactivation of TFEB. Consequently, as damage decreases, TFEB activity decreases. Our results suggest a dynamic interplay between TFEB and mTOR, highlighting a critical role of TFEB in ensuring cellular survival during SIPS induction but becoming dispensable once senescence is established.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Rusu, Elena Cristina; Clavero-Mestres, Helena; SĂĄnchez-Ălvarez, Mario; Veciana-Molins, Marina; Bertran, Laia; Monfort-Lanzas, Pablo; Aguilar, Carmen; Camaron, Javier; Auguet, Teresa
Uncovering hepatic transcriptomic and circulating proteomic signatures in MASH: A meta-analysis and machine learning-based biomarker discovery ArtĂculo de revista
En: Computers in Biology and Medicine, vol. 191, pp. 110170, 2025, ISSN: 1879-0534.
@article{rusu_uncovering_2025,
title = {Uncovering hepatic transcriptomic and circulating proteomic signatures in MASH: A meta-analysis and machine learning-based biomarker discovery},
author = {Elena Cristina Rusu and Helena Clavero-Mestres and Mario SĂĄnchez-Ălvarez and Marina Veciana-Molins and Laia Bertran and Pablo Monfort-Lanzas and Carmen Aguilar and Javier Camaron and Teresa Auguet},
doi = {10.1016/j.compbiomed.2025.110170},
issn = {1879-0534},
year = {2025},
date = {2025-06-01},
journal = {Computers in Biology and Medicine},
volume = {191},
pages = {110170},
abstract = {BACKGROUND: Metabolic-associated steatohepatitis (MASH), the progressive form of metabolic-associated steatotic liver disease (MASLD), poses significant risks for liver fibrosis and cardiovascular complications. Despite extensive research, reliable biomarkers for MASH diagnosis and progression remain elusive. This study aimed to identify hepatic transcriptomic and circulating proteomic signatures specific to MASH, and to develop a machine learning-based biomarker discovery model.
METHODS: A systematic review of RNA-Seq and proteomic datasets was conducted, retrieving 7 hepatic transcriptomics and 3 circulating proteomics studies, encompassing 483 liver samples and 169 serum/plasma samples, respectively. Differential gene and protein expression analyses were performed, and pathways were enriched using gene set enrichment analysis. A machine learning (ML) model was developed to identify MASH-specific biomarkers, utilizing biologically significant protein ratios.
KEY FINDINGS: Hepatic transcriptomic analysis identified 5017 differentially expressed genes (DEGs), with significant enrichment of extracellular matrix (ECM) pathways. Serum proteomics revealed six differentially expressed proteins (DEPs), including complement-related proteins. Integration of transcriptomic and proteomic data highlighted the complement cascade as a key pathway in MASH, with discordant regulation between the liver and circulation. The ML-based biomarker discovery model, utilizing protein ratios, achieved an F1 scores of 0.83 and 0.64 in the training sets and 0.67 in an external validation set.
CONCLUSION: Our findings indicate ECM deregulation and complement system involvement in MASH progression. The novel ML model incorporating protein ratios offers a potential tool for MASH diagnosis. However, further refinement and validation across larger and more diverse cohorts is needed to generalize these results.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: A systematic review of RNA-Seq and proteomic datasets was conducted, retrieving 7 hepatic transcriptomics and 3 circulating proteomics studies, encompassing 483 liver samples and 169 serum/plasma samples, respectively. Differential gene and protein expression analyses were performed, and pathways were enriched using gene set enrichment analysis. A machine learning (ML) model was developed to identify MASH-specific biomarkers, utilizing biologically significant protein ratios.
KEY FINDINGS: Hepatic transcriptomic analysis identified 5017 differentially expressed genes (DEGs), with significant enrichment of extracellular matrix (ECM) pathways. Serum proteomics revealed six differentially expressed proteins (DEPs), including complement-related proteins. Integration of transcriptomic and proteomic data highlighted the complement cascade as a key pathway in MASH, with discordant regulation between the liver and circulation. The ML-based biomarker discovery model, utilizing protein ratios, achieved an F1 scores of 0.83 and 0.64 in the training sets and 0.67 in an external validation set.
CONCLUSION: Our findings indicate ECM deregulation and complement system involvement in MASH progression. The novel ML model incorporating protein ratios offers a potential tool for MASH diagnosis. However, further refinement and validation across larger and more diverse cohorts is needed to generalize these results.
Hofer, Stefanie; Jenny, Marcel; Klein, Angela; Becker, Kathrin; ParrĂĄkovĂĄ, Lucia; Ăberall, Florian; Ganzera, Markus; Fuchs, Dietmar; Hackl, Hubert; Monfort-Lanzas, Pablo; Gostner, Johanna M.
Myrobalan Fruit Extracts Modulate Immunobiochemical Pathways In Vitro ArtĂculo de revista
En: Antioxidants (Basel, Switzerland), vol. 14, no 3, pp. 350, 2025, ISSN: 2076-3921.
@article{hofer_myrobalan_2025,
title = {Myrobalan Fruit Extracts Modulate Immunobiochemical Pathways In Vitro},
author = {Stefanie Hofer and Marcel Jenny and Angela Klein and Kathrin Becker and Lucia ParrĂĄkovĂĄ and Florian Ăberall and Markus Ganzera and Dietmar Fuchs and Hubert Hackl and Pablo Monfort-Lanzas and Johanna M. Gostner},
doi = {10.3390/antiox14030350},
issn = {2076-3921},
year = {2025},
date = {2025-03-01},
journal = {Antioxidants (Basel, Switzerland)},
volume = {14},
number = {3},
pages = {350},
abstract = {Myrobalan fruits are important ingredients of traditional remedies, such as the Ayurvedic formulation Triphala or the Tibetan formulation Bras bu 3. Myrobalan-containing remedies are described to have positive effects on metabolism, the cardiovascular system, and the immune system. The chemical composition of botanical mixtures can be very complex, and it is often impossible to identify individual compounds as specific active ingredients, which suggests a multi-target mode of action. In this in vitro study, the effect of myrobalan extracts in human cell models was investigated to gain more information about the molecular mechanism of action and to find possible synergistic effects. Direct and indirect antioxidant effects were investigated, and the activation of immunobiochemical metabolic pathways involved in the cellular immune response was examined in cell lines treated with extracts of the fruits of Phyllanthus emblica, Terminalia chebula and Terminalia bellirica, as well as a combination of them. In particular, a synergistic effect on the activation of the endogenous antioxidant defence system was observed with the combined treatment of the three fruit extracts. An integrated transcriptome analysis of cells treated with a combination of fruit extracts confirmed an effect on immune pathways, oxidative stress, and detoxification processes. This study shows the modulation of various signalling pathways and cellular processes that may be part of the multi-target mechanism of individual and combined myrobalan fruit extracts. Although the results are limited to in vitro data, they contribute to a better understanding of how botanical mixtures work and provide hypotheses for further research.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Karg, Cornelia A.; Lisandrelli, Rebecca; Schider, GĂŒnther; Monfort-Lanzas, Pablo; Siller, Anita; Schennach, Harald; Moser, Simone; Fuchs, Dietmar; Gostner, Johanna M.
Extracellular spermidine attenuates tryptophan breakdown in mitogen-stimulated peripheral human mononuclear blood cells ArtĂculo de revista
En: Pteridines, vol. 36, no 1, 2025, ISSN: 2195-4720, (Publisher: De Gruyter).
@article{karg_extracellular_2025,
title = {Extracellular spermidine attenuates tryptophan breakdown in mitogen-stimulated peripheral human mononuclear blood cells},
author = {Cornelia A. Karg and Rebecca Lisandrelli and GĂŒnther Schider and Pablo Monfort-Lanzas and Anita Siller and Harald Schennach and Simone Moser and Dietmar Fuchs and Johanna M. Gostner},
url = {https://www.degruyterbrill.com/document/doi/10.1515/pteridines-2025-0054/html},
doi = {10.1515/pteridines-2025-0054},
issn = {2195-4720},
year = {2025},
date = {2025-01-01},
urldate = {2025-10-17},
journal = {Pteridines},
volume = {36},
number = {1},
abstract = {Polyamines, particularly spermidine, play a vital role in regulating cellular functions and influencing processes such as proliferation, ageing, and immune modulation. This study explores the effects of spermidine on the immunoregulatory pathway of tryptophan breakdown, which is mediated by indoleamine 2,3-dioxygenase 1 (IDO-1), as well as on neopterin synthesis, in peripheral blood mononuclear cells. Spermidine treatment was found to suppress IDO-1 activity in mitogen-stimulated cells in a dose-dependent manner without affecting neopterin synthesis. This suppressive effect on tryptophan breakdown contributes to the debate surrounding the health-promoting antioxidant properties of spermidine. However, the divergent regulation of the two immunobiochemical pathways investigated, which share common upstream signalling events, requires further exploration.},
note = {Publisher: De Gruyter},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Monfort-Lanzas, Pablo; Rungger, Katja; Madersbacher, Leonie; Hackl, Hubert
Machine learning to dissect perturbations in complex cellular systems ArtĂculo de revista
En: Computational and Structural Biotechnology Journal, vol. 27, pp. 832â842, 2025, ISSN: 2001-0370.
@article{monfort-lanzas_machine_2025,
title = {Machine learning to dissect perturbations in complex cellular systems},
author = {Pablo Monfort-Lanzas and Katja Rungger and Leonie Madersbacher and Hubert Hackl},
doi = {10.1016/j.csbj.2025.02.028},
issn = {2001-0370},
year = {2025},
date = {2025-01-01},
journal = {Computational and Structural Biotechnology Journal},
volume = {27},
pages = {832â842},
abstract = {Understanding the responses of biological systems to various perturbations, such as genetic, chemical, or environmental challenges, is essential for reconstructing causal network models. Emerging single-cell technologies have become instrumental in elucidating cell states and phenotypes and they have been used in combination with genetic screening. Recent advances in machine learning and artificial intelligence architectures have stimulated the development of computational tools for modeling perturbations and the response to compounds. This study outlined core principles underpinning perturbation analysis and discussed the methodologies and analytical frameworks used to decode drug and genetic perturbation responses, complex multicellular interactions, and network dynamics. The current tools used for various applications were overviewed. These developments hold great promise for improving drug development and personalized medicine. Foundation models and perturbation cell and tissue atlases offer immense potential for advancing our understanding of cellular behavior and disease mechanisms.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Monfort-Lanzas, Pablo; Gostner, Johanna M.; Hackl, Hubert
Modeling omics dose-response at the pathway level with DoseRider ArtĂculo de revista
En: Computational and Structural Biotechnology Journal, vol. 27, pp. 1440â1448, 2025, ISSN: 2001-0370.
@article{monfort-lanzas_modeling_2025,
title = {Modeling omics dose-response at the pathway level with DoseRider},
author = {Pablo Monfort-Lanzas and Johanna M. Gostner and Hubert Hackl},
doi = {10.1016/j.csbj.2025.04.004},
issn = {2001-0370},
year = {2025},
date = {2025-01-01},
journal = {Computational and Structural Biotechnology Journal},
volume = {27},
pages = {1440â1448},
abstract = {The generation of omics data sets has become an important approach in modern pharmacological and toxicological research as it can provide mechanistic and quantitative information on a large scale. Analyses of these data frequently revealed a non-linear dose-response relationship underscoring the importance of the modeling process to infer biological exposure limits. A number of tools have been developed for dose-response modeling and various thresholds have been defined as a quantitative representation of the effect of a substance, such as effective concentrations or benchmark doses (BMD). Here we present DoseRider an easy-to-use web application and a companion R package for linear and non-linear dose-response modeling and assessment of BMD at the level of biological pathways or signatures using generalized mixed effect models. This approach allows to analyze custom or provided multi-omics data such as RNA sequencing or metabolomics data and its annotation of a collection of pathways and gene sets from various species. Moreover, we introduce the concept of the trend change doses (TCDs) as a numerical descriptor of effects derived from complex dose-response curves. The usability of DoseRider was demonstrated by analyses of RNA sequencing data of bisphenol AF (BPAF) treatment of a human breast cancer cell line (MCF-7) at 8 different concentrations using gene sets for chemical and genetic perturbations (MSigDB). The BMD for BPAF and a set of genes upregulated by estrogen in breast cancer was 0.2âŻÂ”M (95âŻ%-CI 0.1-0.5âŻÂ”M) and the lowest TCD (TCD1) was 0.003âŻÂ”M (95âŻ%-CI 0.0006-0.01âŻÂ”M). The comprehensive presentation of the results underlines the suitability of the system for pharmacogenomics, toxicogenomics, and applications beyond.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2024
Rusu, Elena Cristina; Monfort-Lanzas, Pablo; Bertran, Laia; Barrientos-Riosalido, Andrea; Solé, Emilia; Mahmoudian, Razieh; Aguilar, Carmen; Briansó, Silvia; Mohamed, Fadel; Garcia, Susana; Camaron, Javier; Auguet, Teresa
Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights ArtĂculo de revista
En: Computers in Biology and Medicine, vol. 175, pp. 108507, 2024, ISSN: 1879-0534.
@article{rusu_towards_2024,
title = {Towards understanding post-COVID-19 condition: A systematic meta-analysis of transcriptomic alterations with sex-specific insights},
author = {Elena Cristina Rusu and Pablo Monfort-Lanzas and Laia Bertran and Andrea Barrientos-Riosalido and Emilia Solé and Razieh Mahmoudian and Carmen Aguilar and Silvia Briansó and Fadel Mohamed and Susana Garcia and Javier Camaron and Teresa Auguet},
doi = {10.1016/j.compbiomed.2024.108507},
issn = {1879-0534},
year = {2024},
date = {2024-06-01},
journal = {Computers in Biology and Medicine},
volume = {175},
pages = {108507},
abstract = {BACKGROUND: Post COVID-19 Condition (PCC), characterized by lingering symptoms post-acute COVID-19, poses clinical challenges, highlighting the need to understand its underlying molecular mechanisms. This meta-analysis aims to shed light on the transcriptomic landscapes and sex-specific molecular dynamics intrinsic to PCC.
METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns.
KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions.
CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: A systematic review identified three studies suitable for comprehensive meta-analysis, encompassing 135 samples (57 PCC subjects and 78 recovered subjects). We performed meta-analysis on differential gene expression, a gene set enrichment analysis of Reactome pathways, and weighted gene co-expression network analysis (WGCNA). We performed a drug and disease enrichment analysis and also assessed sex-specific differences in expression patterns.
KEY FINDINGS: A clear difference was observed in the transcriptomic profiles of PCC subjects, with 530 differentially expressed genes (DEGs) identified. Enrichment analysis revealed that the altered pathways were predominantly implicated in cell cycle processes, immune dysregulation and histone modifications. Antioxidant compounds such as hesperitin were predominantly linked to the hub genes of the DEGs. Sex-specific analyses highlighted disparities in DEGs and altered pathways in male and female PCC patients, revealing a difference in the expression of ribosomal proteins. PCC in men was mostly linked to neuro-cardiovascular disorders, while women exhibited more diverse disorders, with a high index of respiratory conditions.
CONCLUSION: Our study reveals the intricate molecular processes underlying PCC, highlighting that the differences in molecular dynamics between males and females could be key to understanding and effectively managing the varied symptomatology of this condition.
Monfort-Lanzas, Pablo; Rusu, Elena Cristina; Parrakova, Lucia; Karg, Cornelia A.; Kernbichler, Dorina-Elina; Rieder, Dietmar; Lackner, Peter; Hackl, Hubert; Gostner, Johanna M.
ExonSurfer: a web-tool to design primers at exon-exon junctions ArtĂculo de revista
En: BMC genomics, vol. 25, no 1, pp. 594, 2024, ISSN: 1471-2164.
@article{monfort-lanzas_exonsurfer_2024,
title = {ExonSurfer: a web-tool to design primers at exon-exon junctions},
author = {Pablo Monfort-Lanzas and Elena Cristina Rusu and Lucia Parrakova and Cornelia A. Karg and Dorina-Elina Kernbichler and Dietmar Rieder and Peter Lackner and Hubert Hackl and Johanna M. Gostner},
doi = {10.1186/s12864-024-10456-2},
issn = {1471-2164},
year = {2024},
date = {2024-06-01},
journal = {BMC genomics},
volume = {25},
number = {1},
pages = {594},
abstract = {BACKGROUND: Reverse transcription quantitative PCR (RT-qPCR) with intercalating dyes is one of the main techniques to assess gene expression levels used in basic and applied research as well as in diagnostics. However, primer design for RT-qPCR can be complex due to the high demands on primer quality. Primers are best placed on exon junctions, should avoid polymorphic regions, be specific to the target transcripts and also prevent genomic amplification accurately, among others. Current software tools manage to meet all the necessary criteria only insufficiently. Here, we present ExonSurfer, a novel, user-friendly web-tool for qPCR primer design.
RESULTS: ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets.
CONCLUSION: ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
RESULTS: ExonSurfer combines the different steps of the primer design process, encompassing target selection, specificity and self-complementarity assessment, and the avoidance of issues arising from polymorphisms. Amplification of potentially contaminating genomic DNA is avoided by designing primers on exon-exon junctions, moreover, a genomic alignment is performed to filter the primers accordingly and inform the user of any predicted interaction. In order to test the whole performance of the application, we designed primer pairs for 26 targets and checked both primer efficiency, amplicon melting temperature and length and confirmed the targeted amplicon by Sanger sequencing. Most of the tested primers accurately and selectively amplified the corresponding targets.
CONCLUSION: ExonSurfer offers a comprehensive end-to-end primer design, guaranteeing transcript-specific amplification. The user interface is intuitive, providing essential specificity and amplicon details. The tool can also be used by command line and the source code is available. Overall, we expect ExonSurfer to facilitate RT-qPCR set-up for researchers in many fields.
Jaylet, Thomas; Coustillet, Thibaut; Smith, Nicola M.; Viviani, Barbara; Lindeman, Birgitte; Vergauwen, Lucia; Myhre, Oddvar; Yarar, Nurettin; Gostner, Johanna M.; Monfort-Lanzas, Pablo; Jornod, Florence; Holbech, Henrik; Coumoul, Xavier; Sarigiannis, Dimosthenis A.; Antczak, Philipp; Bal-Price, Anna; Fritsche, Ellen; Kuchovska, Eliska; Stratidakis, Antonios K.; Barouki, Robert; Kim, Min Ji; Taboureau, Olivier; Wojewodzic, Marcin W.; Knapen, Dries; Audouze, Karine
Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps ArtĂculo de revista
En: Frontiers in Toxicology, vol. 6, pp. 1285768, 2024, ISSN: 2673-3080.
@article{jaylet_comprehensive_2024,
title = {Comprehensive mapping of the AOP-Wiki database: identifying biological and disease gaps},
author = {Thomas Jaylet and Thibaut Coustillet and Nicola M. Smith and Barbara Viviani and Birgitte Lindeman and Lucia Vergauwen and Oddvar Myhre and Nurettin Yarar and Johanna M. Gostner and Pablo Monfort-Lanzas and Florence Jornod and Henrik Holbech and Xavier Coumoul and Dimosthenis A. Sarigiannis and Philipp Antczak and Anna Bal-Price and Ellen Fritsche and Eliska Kuchovska and Antonios K. Stratidakis and Robert Barouki and Min Ji Kim and Olivier Taboureau and Marcin W. Wojewodzic and Dries Knapen and Karine Audouze},
doi = {10.3389/ftox.2024.1285768},
issn = {2673-3080},
year = {2024},
date = {2024-01-01},
journal = {Frontiers in Toxicology},
volume = {6},
pages = {1285768},
abstract = {Introduction: The Adverse Outcome Pathway (AOP) concept facilitates rapid hazard assessment for human health risks. AOPs are constantly evolving, their number is growing, and they are referenced in the AOP-Wiki database, which is supported by the OECD. Here, we present a study that aims at identifying well-defined biological areas, as well as gaps within the AOP-Wiki for future research needs. It does not intend to provide a systematic and comprehensive summary of the available literature on AOPs but summarizes and maps biological knowledge and diseases represented by the already developed AOPs (with OECD endorsed status or under validation). Methods: Knowledge from the AOP-Wiki database were extracted and prepared for analysis using a multi-step procedure. An automatic mapping of the existing information on AOPs (i.e., genes/proteins and diseases) was performed using bioinformatics tools (i.e., overrepresentation analysis using Gene Ontology and DisGeNET), allowing both the classification of AOPs and the development of AOP networks (AOPN). Results: AOPs related to diseases of the genitourinary system, neoplasms and developmental anomalies are the most frequently investigated on the AOP-Wiki. An evaluation of the three priority cases (i.e., immunotoxicity and non-genotoxic carcinogenesis, endocrine and metabolic disruption, and developmental and adult neurotoxicity) of the EU-funded PARC project (Partnership for the Risk Assessment of Chemicals) are presented. These were used to highlight under- and over-represented adverse outcomes and to identify and prioritize gaps for further research. Discussion: These results contribute to a more comprehensive understanding of the adverse effects associated with the molecular events in AOPs, and aid in refining risk assessment for stressors and mitigation strategies. Moreover, the FAIRness (i.e., data which meets principles of findability, accessibility, interoperability, and reusability (FAIR)) of the AOPs appears to be an important consideration for further development.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Hargitai, Rita; ParrĂĄkovĂĄ, Lucia; SzatmĂĄri, TĂŒnde; Monfort-Lanzas, Pablo; Galbiati, Valentina; Audouze, Karine; Jornod, Florence; Staal, Yvonne C. M.; Burla, Sabina; Chary, Aline; Gutleb, Arno C.; Lumniczky, Katalin; Vandebriel, Rob J.; Gostner, Johanna M.
Chemical respiratory sensitization-Current status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers ArtĂculo de revista
En: Frontiers in Toxicology, vol. 6, pp. 1331803, 2024, ISSN: 2673-3080.
@article{hargitai_chemical_2024,
title = {Chemical respiratory sensitization-Current status of mechanistic understanding, knowledge gaps and possible identification methods of sensitizers},
author = {Rita Hargitai and Lucia ParrĂĄkovĂĄ and TĂŒnde SzatmĂĄri and Pablo Monfort-Lanzas and Valentina Galbiati and Karine Audouze and Florence Jornod and Yvonne C. M. Staal and Sabina Burla and Aline Chary and Arno C. Gutleb and Katalin Lumniczky and Rob J. Vandebriel and Johanna M. Gostner},
doi = {10.3389/ftox.2024.1331803},
issn = {2673-3080},
year = {2024},
date = {2024-01-01},
journal = {Frontiers in Toxicology},
volume = {6},
pages = {1331803},
abstract = {Respiratory sensitization is a complex immunological process eventually leading to hypersensitivity following re-exposure to the chemical. A frequent consequence is occupational asthma, which may occur after long latency periods. Although chemical-induced respiratory hypersensitivity has been known for decades, there are currently no comprehensive and validated approaches available for the prospective identification of chemicals that induce respiratory sensitization, while the expectations of new approach methodologies (NAMs) are high. A great hope is that due to a better understanding of the molecular key events, new methods can be developed now. However, this is a big challenge due to the different chemical classes to which respiratory sensitizers belong, as well as because of the complexity of the response and the late manifestation of symptoms. In this review article, the current information on respiratory sensitization related processes is summarized by introducing it in the available adverse outcome pathway (AOP) concept. Potentially useful models for prediction are discussed. Knowledge gaps and gaps of regulatory concern are identified.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Gronauer, Raphael; Madersbacher, Leonie; Monfort-Lanzas, Pablo; Floriani, Gabriel; Sprung, Susanne; Zeimet, Alain Gustave; Marth, Christian; Fiegl, Heidelinde; Hackl, Hubert
Integrated immunogenomic analyses of high-grade serous ovarian cancer reveal vulnerability to combination immunotherapy ArtĂculo de revista
En: Frontiers in Immunology, vol. 15, pp. 1489235, 2024, ISSN: 1664-3224.
@article{gronauer_integrated_2024,
title = {Integrated immunogenomic analyses of high-grade serous ovarian cancer reveal vulnerability to combination immunotherapy},
author = {Raphael Gronauer and Leonie Madersbacher and Pablo Monfort-Lanzas and Gabriel Floriani and Susanne Sprung and Alain Gustave Zeimet and Christian Marth and Heidelinde Fiegl and Hubert Hackl},
doi = {10.3389/fimmu.2024.1489235},
issn = {1664-3224},
year = {2024},
date = {2024-01-01},
journal = {Frontiers in Immunology},
volume = {15},
pages = {1489235},
abstract = {BACKGROUND: The efficacy of immunotherapies in high-grade serous ovarian cancer (HGSOC) is limited, but clinical trials investigating the potential of combination immunotherapy including poly-ADP-ribose polymerase inhibitors (PARPis) are ongoing. Homologous recombination repair deficiency or BRCAness and the composition of the tumor microenvironment appear to play a critical role in determining the therapeutic response.
METHODS: We conducted comprehensive immunogenomic analyses of HGSOC using data from several patient cohorts. Machine learning methods were used to develop a classification model for BRCAness from gene expression data. Integrated analysis of bulk and single-cell RNA sequencing data was used to delineate the tumor immune microenvironment and was validated by immunohistochemistry. The impact of PARPi and BRCA1 mutations on the activation of immune-related pathways was studied using ovarian cancer cell lines, RNA sequencing, and immunofluorescence analysis.
RESULTS: We identified a 24-gene signature that predicts BRCAness. Comprehensive immunogenomic analyses across patient cohorts identified samples with BRCAness and high immune infiltration. Further characterization of these samples revealed increased infiltration of immunosuppressive cells, including tumor-associated macrophages expressing TREM2, C1QA, and LILRB4, as specified by single-cell RNA sequencing data and gene expression analysis of samples from patients receiving combination therapy with PARPi and anti-PD-1. Our findings show also that genomic instability and PARPi activated the cGAS-STING signaling pathway in vitro and the downstream innate immune response in a similar manner to HGSOC patients with BRCAness status. Finally, we have developed a web application (https://ovrseq.icbi.at) and an associated R package OvRSeq, which allow for comprehensive characterization of ovarian cancer patient samples and assessment of a vulnerability score that enables stratification of patients to predict response to the combination immunotherapy.
CONCLUSIONS: Genomic instability in HGSOC affects the tumor immune environment, and TAMs play a crucial role in modulating the immune response. Based on various datasets, we have developed a diagnostic application that uses RNA sequencing data not only to comprehensively characterize HGSOC but also to predict vulnerability and response to combination immunotherapy.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
METHODS: We conducted comprehensive immunogenomic analyses of HGSOC using data from several patient cohorts. Machine learning methods were used to develop a classification model for BRCAness from gene expression data. Integrated analysis of bulk and single-cell RNA sequencing data was used to delineate the tumor immune microenvironment and was validated by immunohistochemistry. The impact of PARPi and BRCA1 mutations on the activation of immune-related pathways was studied using ovarian cancer cell lines, RNA sequencing, and immunofluorescence analysis.
RESULTS: We identified a 24-gene signature that predicts BRCAness. Comprehensive immunogenomic analyses across patient cohorts identified samples with BRCAness and high immune infiltration. Further characterization of these samples revealed increased infiltration of immunosuppressive cells, including tumor-associated macrophages expressing TREM2, C1QA, and LILRB4, as specified by single-cell RNA sequencing data and gene expression analysis of samples from patients receiving combination therapy with PARPi and anti-PD-1. Our findings show also that genomic instability and PARPi activated the cGAS-STING signaling pathway in vitro and the downstream innate immune response in a similar manner to HGSOC patients with BRCAness status. Finally, we have developed a web application (https://ovrseq.icbi.at) and an associated R package OvRSeq, which allow for comprehensive characterization of ovarian cancer patient samples and assessment of a vulnerability score that enables stratification of patients to predict response to the combination immunotherapy.
CONCLUSIONS: Genomic instability in HGSOC affects the tumor immune environment, and TAMs play a crucial role in modulating the immune response. Based on various datasets, we have developed a diagnostic application that uses RNA sequencing data not only to comprehensively characterize HGSOC but also to predict vulnerability and response to combination immunotherapy.
Monfort-Lanzas, Pablo; Gronauer, Raphael; Balaz, Melanie; Floriani, Gabriel; Hackl, Hubert
Application of artificial intelligence in immuno-oncology Book Section
En: Reference Module in Biomedical Sciences, Elsevier, 2024, ISBN: 978-0-12-801238-3.
@incollection{monfort-lanzas_application_2024,
title = {Application of artificial intelligence in immuno-oncology},
author = {Pablo Monfort-Lanzas and Raphael Gronauer and Melanie Balaz and Gabriel Floriani and Hubert Hackl},
url = {https://www.sciencedirect.com/science/article/pii/B9780443140648000175},
doi = {10.1016/B978-0-443-14064-8.00017-5},
isbn = {978-0-12-801238-3},
year = {2024},
date = {2024-01-01},
urldate = {2025-10-17},
booktitle = {Reference Module in Biomedical Sciences},
publisher = {Elsevier},
abstract = {Artificial intelligence (AI) has significantly influenced biomedicine, particularly in the field of immuno-oncology. This work explores the current advancements and challenges in AI emphasizing their application in immuno-oncology. We discuss various AI principles and architectures, such as transformer technology, highlighting their predictive and generative capabilities. One of the main challenges in immuno-oncology is predicting responses to immunotherapy. We describe AI-driven methods for developing predictive biomarkers using digital pathology, radiomics, and transcriptomics data. Recent AI successes in this area include the activation of T cells by antigens and the analysis of the tumor immune microenvironment, especially in cell annotation.},
keywords = {},
pubstate = {published},
tppubtype = {incollection}
}
2023
Obermoser, Katharina; Brigo, Natascha; Schroll, Andrea; Monfort-Lanzas, Pablo; Gostner, Johanna M.; Engl, Sabine; Geisler, Simon; Knoll, Miriam; Schennach, Harald; Weiss, GĂŒnter; Fuchs, Dietmar; Bellmann-Weiler, Rosa; Kurz, Katharina
Positive Effects of Probiotic Therapy in Patients with Post-Infectious Fatigue ArtĂculo de revista
En: Metabolites, vol. 13, no 5, pp. 639, 2023, ISSN: 2218-1989.
@article{obermoser_positive_2023,
title = {Positive Effects of Probiotic Therapy in Patients with Post-Infectious Fatigue},
author = {Katharina Obermoser and Natascha Brigo and Andrea Schroll and Pablo Monfort-Lanzas and Johanna M. Gostner and Sabine Engl and Simon Geisler and Miriam Knoll and Harald Schennach and GĂŒnter Weiss and Dietmar Fuchs and Rosa Bellmann-Weiler and Katharina Kurz},
doi = {10.3390/metabo13050639},
issn = {2218-1989},
year = {2023},
date = {2023-05-01},
journal = {Metabolites},
volume = {13},
number = {5},
pages = {639},
abstract = {Post-infectious fatigue is a common complication that can lead to decreased physical efficiency, depression, and impaired quality of life. Dysbiosis of the gut microbiota has been proposed as a contributing factor, as the gut-brain axis plays an important role in regulating physical and mental health. This pilot study aimed to investigate the severity of fatigue and depression, as well as the quality of life of 70 patients with post-infectious fatigue who received a multi-strain probiotic preparation or placebo in a double-blind, placebo-controlled trial. Patients completed questionnaires to assess their fatigue (fatigue severity scale (FSS)), mood (Beck Depression Inventory II (BDI-II)), and quality of life (short form-36 (SF-36)) at baseline and after 3 and 6 months of treatment. Routine laboratory parameters were also assessed, including immune-mediated changes in tryptophan and phenylalanine metabolism. The intervention was effective in improving fatigue, mood, and quality of life in both the probiotic and placebo groups, with greater improvements seen in the probiotic group. FSS and BDI-II scores declined significantly under treatment with both probiotics and placebo, but patients who received probiotics had significantly lower FSS (p < 0.001) and BDI-II (p < 0.001) scores after 6 months. Quality of life scores improved significantly in patients who received probiotics (p < 0.001), while patients taking a placebo only saw improvements in the "Physical limitation" and "Energy/Fatigue" subcategories. After 6 months neopterin was higher in patients receiving placebo, while no longitudinal changes in interferon-gamma mediated biochemical pathways were observed. These findings suggest that probiotics may be a promising intervention for improving the health of patients with post-infectious fatigue, potentially through modulating the gut-brain axis.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Taenzer, Maja; Löffler-Ragg, Judith; Schroll, Andrea; Monfort-Lanzas, Pablo; Engl, Sabine; Weiss, GĂŒnter; Brigo, Natascha; Kurz, Katharina
Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study ArtĂculo de revista
En: International journal of tryptophan research: IJTR, vol. 16, pp. 11786469231220781, 2023, ISSN: 1178-6469.
@article{taenzer_urine_2023,
title = {Urine Metabolite Analysis to Identify Pathomechanisms of Long COVID: A Pilot Study},
author = {Maja Taenzer and Judith Löffler-Ragg and Andrea Schroll and Pablo Monfort-Lanzas and Sabine Engl and GĂŒnter Weiss and Natascha Brigo and Katharina Kurz},
doi = {10.1177/11786469231220781},
issn = {1178-6469},
year = {2023},
date = {2023-01-01},
journal = {International journal of tryptophan research: IJTR},
volume = {16},
pages = {11786469231220781},
abstract = {BACKGROUND: Around 10% of people who had COVID-9 infection suffer from persistent symptoms such as fatigue, dyspnoea, chest pain, arthralgia/myalgia, sleep disturbances, cognitive dysfunction and impairment of mental health. Different underlying pathomechanisms appear to be involved, in particular inflammation, alterations in amino acid metabolism, autonomic dysfunction and gut dysbiosis.
AIM: As routine tests are often inconspicuous in patients with Long COVID (LC), similarly to patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), accessible biomarkers indicating dysregulation of specific pathways are urgently needed to identify underlying pathomechanisms and enable personalized medicine treatment. Within this pilot study we aimed to proof traceability of altered metabolism by urine analysis. PATIENTS AND METHODS: Urine metabolome analyses were performed to investigate the metabolic signature of patients with LC (nâ=â25; 20 women, 5 men) in comparison to healthy controls (Ctrl},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
AIM: As routine tests are often inconspicuous in patients with Long COVID (LC), similarly to patients suffering from myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), accessible biomarkers indicating dysregulation of specific pathways are urgently needed to identify underlying pathomechanisms and enable personalized medicine treatment. Within this pilot study we aimed to proof traceability of altered metabolism by urine analysis. PATIENTS AND METHODS: Urine metabolome analyses were performed to investigate the metabolic signature of patients with LC (nâ=â25; 20 women, 5 men) in comparison to healthy controls (Ctrl
DĂaz, Magdalena; Monfort-Lanzas, Pablo; Quiroz-Moreno, Cristian; Rivadeneira, Erika; Castillejo, Pablo; Arnau, Vicente; DĂaz, Wladimiro; Agathos, Spiros N.; Sangari, FĂ©lix J.; JarrĂn-V, Pablo; Molina, C. Alfonso
The microbiome of the ice-capped Cayambe Volcanic Complex in Ecuador ArtĂculo de revista
En: Frontiers in Microbiology, vol. 14, pp. 1154815, 2023, ISSN: 1664-302X.
@article{diaz_microbiome_2023,
title = {The microbiome of the ice-capped Cayambe Volcanic Complex in Ecuador},
author = {Magdalena DĂaz and Pablo Monfort-Lanzas and Cristian Quiroz-Moreno and Erika Rivadeneira and Pablo Castillejo and Vicente Arnau and Wladimiro DĂaz and Spiros N. Agathos and FĂ©lix J. Sangari and Pablo JarrĂn-V and C. Alfonso Molina},
doi = {10.3389/fmicb.2023.1154815},
issn = {1664-302X},
year = {2023},
date = {2023-01-01},
journal = {Frontiers in Microbiology},
volume = {14},
pages = {1154815},
abstract = {A major challenge in microbial ecology is to understand the principles and processes by which microbes associate and interact in community assemblages. Microbial communities in mountain glaciers are unique as first colonizers and nutrient enrichment drivers for downstream ecosystems. However, mountain glaciers have been distinctively sensitive to climate perturbations and have suffered a severe retreat over the past 40 years, compelling us to understand glacier ecosystems before their disappearance. This is the first study in an Andean glacier in Ecuador offering insights into the relationship of physicochemical variables and altitude on the diversity and structure of bacterial communities. Our study covered extreme Andean altitudes at the Cayambe Volcanic Complex, from 4,783 to 5,583 masl. Glacier soil and ice samples were used as the source for 16S rRNA gene amplicon libraries. We found (1) effects of altitude on diversity and community structure, (2) the presence of few significantly correlated nutrients to community structure, (3) sharp differences between glacier soil and glacier ice in diversity and community structure, where, as quantified by the Shannon Îł-diversity distribution, the meta-community in glacier soil showed more diversity than in glacier ice; this pattern was related to the higher variability of the physicochemical distribution of variables in the former substrate, and (4) significantly abundant genera associated with either high or low altitudes that could serve as biomarkers for studies on climate change. Our results provide the first assessment of these unexplored communities, before their potential disappearance due to glacier retreat and climate change.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
2022
Monfort-Lanzas, Pablo; Gronauer, Raphael; Madersbacher, Leonie; Schatz, Christoph; Rieder, Dietmar; Hackl, Hubert
MIO: microRNA target analysis system for immuno-oncology ArtĂculo de revista
En: Bioinformatics (Oxford, England), vol. 38, no 14, pp. 3665â3667, 2022, ISSN: 1367-4811.
@article{monfort-lanzas_mio_2022,
title = {MIO: microRNA target analysis system for immuno-oncology},
author = {Pablo Monfort-Lanzas and Raphael Gronauer and Leonie Madersbacher and Christoph Schatz and Dietmar Rieder and Hubert Hackl},
doi = {10.1093/bioinformatics/btac366},
issn = {1367-4811},
year = {2022},
date = {2022-07-01},
journal = {Bioinformatics (Oxford, England)},
volume = {38},
number = {14},
pages = {3665â3667},
abstract = {SUMMARY: MicroRNAs have been shown to be able to modulate the tumor microenvironment and the immune response and hence could be interesting biomarkers and therapeutic targets in immuno-oncology; however, dedicated analysis tools are missing. Here, we present a user-friendly web platform MIO and a Python toolkit miopy integrating various methods for visualization and analysis of provided or custom bulk microRNA and gene expression data. We include regularized regression and survival analysis and provide information of 40 microRNA target prediction tools as well as a collection of curated immune related gene and microRNA signatures and processed TCGA data including estimations of infiltrated immune cells and the immunophenoscore. The integration of several machine learning methods enables the selection of prognostic and predictive microRNAs and gene interaction network biomarkers.
AVAILABILITY AND IMPLEMENTATION: https://mio.icbi.at, https://github.com/icbi-lab/mio and https://github.com/icbi-lab/miopy.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
AVAILABILITY AND IMPLEMENTATION: https://mio.icbi.at, https://github.com/icbi-lab/mio and https://github.com/icbi-lab/miopy.
SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
DĂaz, Magdalena; Quiroz-Moreno, Cristian; JarrĂn-V, Pablo; Piquer-Esteban, Samuel; Monfort-Lanzas, Pablo; Rivadeneira, Erika; Castillejo, Pablo; Arnau, Vicente; DĂaz, Wladimiro; Sangari, FĂ©lix J.; Molina, C. Alfonso
Soil Bacterial Community Along an Altitudinal Gradient in the Sumaco, a Stratovolcano in the Amazon Region ArtĂculo de revista
En: Frontiers in Forests and Global Change, vol. 5, 2022, ISSN: 2624-893X, (Publisher: Frontiers).
@article{diaz_soil_2022,
title = {Soil Bacterial Community Along an Altitudinal Gradient in the Sumaco, a Stratovolcano in the Amazon Region},
author = {Magdalena DĂaz and Cristian Quiroz-Moreno and Pablo JarrĂn-V and Samuel Piquer-Esteban and Pablo Monfort-Lanzas and Erika Rivadeneira and Pablo Castillejo and Vicente Arnau and Wladimiro DĂaz and FĂ©lix J. Sangari and C. Alfonso Molina},
url = {https://www.frontiersin.org/journals/forests-and-global-change/articles/10.3389/ffgc.2022.738568/full},
doi = {10.3389/ffgc.2022.738568},
issn = {2624-893X},
year = {2022},
date = {2022-03-01},
urldate = {2025-10-17},
journal = {Frontiers in Forests and Global Change},
volume = {5},
abstract = {Our study is a pioneering exploration of the microbiome in the soil of the Sumaco stratovolcano and an assessment of the effects of an elevational gradient and related physicochemical soil parameters on richness and community structure. The Sumaco, as an isolated Amazonian stratovolcano, may be among one of the least studied ecosystems in Ecuador and perhaps the Amazon region. Universal patterns remain unresolved or available information inconclusive to establish a supported consensus on general governing processes by which elevation and its associated environmental gradients may determine the microbial richness and community structure. We tested a recent proposal on how microbial diversity responds to montane gradients, placing a central role in soils as potentially independent of altitude along an elevational gradient. Correlations and effects among soil physicochemical parameters and altitude were contrasted against richness and community structure through quantitative ecology. The most informative physicochemical parameter in our assessment of bacterial community structure was neither pH nor altitude, but sulfur, which was mostly independent of the other tested parameters. We established a positive effect of richness by parameters associated with metallic cations such as Mn2+, and CEC, which were negatively correlated to altitude and pH. The possible relation between the significant role of sulfur on bacteria community structure with the unique geological origin of the Sumaco stratovolcano should be examined in the context of specialized sulfur metabolisms and additional information on community structure and environmental constraints. Our study establishes an initial baseline for further explorations of microbial diversity in this unexplored tropical stratovolcano},
note = {Publisher: Frontiers},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
