Group Leader
SOCIAL
CONTACTS
+39 049 827 6260
+39 049 827 6269
Profile
BIOGRAPHY
Silvio C. E. Tosatto is currently Full Professor of Bioinformatics and Head of the BioComputing UP lab at the Department of Biomedical Sciences of the University of Padua (Italy). Within ELIXIR, the European infrastructure for blife science data, he is deputy Head of Node of ELIXIR Italy, ExCo of the Data Platform, co-lead of the Cellular & Molecular Research priority area as well as co-lead of the Machine Learning focus group.
ACADEMIC POSITION
Full professor
since (10/2016)
DEGREES
- 2002 – PhD (Dr. rer. nat., Grade: Magna cum laude) in bioinformatics (computer science)
Universität Mannheim – Germany - 1998 – Graduate in Computer Science & Business Administration (Diplom Wirtschaftsinformatiker)
Universität Mannheim – Germany
LANGUAGES
English
Spanish
German
Italian
(Fluent)
(Fluent)
(Native)
(Native)
Publications
2024
Journal Articles
1.
Alessio Del Conte; Giorgia F Camagni; Damiano Clementel; Giovanni Minervini; Alexander Miguel Monzon; Carlo Ferrari; Damiano Piovesan; Silvio C. E Tosatto
RING 4.0: Faster residue interaction networks with novel interaction types across over 35,000 different chemical structures Journal Article
In: Nucleic Acids Research, vol. 52, no. W1, pp. W306 – W312, 2024, ISSN: 03051048, (Cited by: 5; All Open Access, Gold Open Access).
@article{DelConte2024W306,
title = {RING 4.0: Faster residue interaction networks with novel interaction types across over 35,000 different chemical structures},
author = { Alessio Del Conte and Giorgia F Camagni and Damiano Clementel and Giovanni Minervini and Alexander Miguel Monzon and Carlo Ferrari and Damiano Piovesan and Silvio C. E Tosatto},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85197788039&doi=10.1093%2fnar%2fgkae337&partnerID=40&md5=bca70d16fbb39f5466a3957673ef9eef},
doi = {10.1093/nar/gkae337},
issn = {03051048},
year = {2024},
date = {2024-01-01},
journal = {Nucleic Acids Research},
volume = {52},
number = {W1},
pages = {W306 – W312},
publisher = {Oxford University Press},
abstract = {Residue interaction networks (RINs) are a valuable approach for representing contacts in protein structures. RINs have been widely used in various research areas, including the analysis of mutation effects, domain-domain communication, catalytic activity, and molecular dynamics simulations. The RING server is a powerful tool to calculate non-covalent molecular interactions based on geometrical parameters, providing high-quality and reliable results. Here, we introduce RING 4.0, which includes significant enhancements for identifying both covalent and non-covalent bonds in protein structures. It now encompasses seven different interaction types, with the addition of π-hydrogen, halogen bonds and metal ion coordination sites. The definitions of all available bond types have also been refined and RING can now process the complete PDB chemical component dictionary (over 35000 different molecules) which provides atom names and covalent connectivity information for all known ligands. Optimization of the software has improved execution time by an order of magnitude. The RING web server has been redesigned to provide a more engaging and interactive user experience, incorporating new visualization tools. Users can now visualize all types of interactions simultaneously in the structure viewer and network component. The web server, including extensive help and tutorials, is available from URL: https://ring.biocomputingup.it/. © 2024 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.},
note = {Cited by: 5; All Open Access, Gold Open Access},
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pubstate = {published},
tppubtype = {article}
}
Residue interaction networks (RINs) are a valuable approach for representing contacts in protein structures. RINs have been widely used in various research areas, including the analysis of mutation effects, domain-domain communication, catalytic activity, and molecular dynamics simulations. The RING server is a powerful tool to calculate non-covalent molecular interactions based on geometrical parameters, providing high-quality and reliable results. Here, we introduce RING 4.0, which includes significant enhancements for identifying both covalent and non-covalent bonds in protein structures. It now encompasses seven different interaction types, with the addition of π-hydrogen, halogen bonds and metal ion coordination sites. The definitions of all available bond types have also been refined and RING can now process the complete PDB chemical component dictionary (over 35000 different molecules) which provides atom names and covalent connectivity information for all known ligands. Optimization of the software has improved execution time by an order of magnitude. The RING web server has been redesigned to provide a more engaging and interactive user experience, incorporating new visualization tools. Users can now visualize all types of interactions simultaneously in the structure viewer and network component. The web server, including extensive help and tutorials, is available from URL: https://ring.biocomputingup.it/. © 2024 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.
2.
Damiano Piovesan; Davide Zago; Parnal Joshi; M. Clara De Paolis Kaluza; Mahta Mehdiabadi; Rashika Ramola; Alexander Miguel Monzon; Walter Reade; Iddo Friedberg; Predrag Radivojac; Silvio C. E. Tosatto
CAFA-evaluator: a Python tool for benchmarking ontological classification methods Journal Article
In: Bioinformatics Advances, vol. 4, no. 1, 2024, ISSN: 26350041, (Cited by: 2; All Open Access, Gold Open Access).
@article{Piovesan2024,
title = {CAFA-evaluator: a Python tool for benchmarking ontological classification methods},
author = { Damiano Piovesan and Davide Zago and Parnal Joshi and M. Clara De Paolis Kaluza and Mahta Mehdiabadi and Rashika Ramola and Alexander Miguel Monzon and Walter Reade and Iddo Friedberg and Predrag Radivojac and Silvio C. E. Tosatto},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188993912&doi=10.1093%2fbioadv%2fvbae043&partnerID=40&md5=b6e09ea188a60708097f5bc31ba115dd},
doi = {10.1093/bioadv/vbae043},
issn = {26350041},
year = {2024},
date = {2024-01-01},
journal = {Bioinformatics Advances},
volume = {4},
number = {1},
publisher = {Oxford University Press},
abstract = {We present CAFA-evaluator, a powerful Python program designed to evaluate the performance of prediction methods on targets with hierarchical concept dependencies. It generalizes multi-label evaluation to modern ontologies where the prediction targets are drawn from a directed acyclic graph and achieves high efficiency by leveraging matrix computation and topological sorting. The program requirements include a small number of standard Python libraries, making CAFA-evaluator easy to maintain. The code replicates the Critical Assessment of protein Function Annotation (CAFA) benchmarking, which evaluates predictions of the consistent subgraphs in Gene Ontology. Owing to its reliability and accuracy, the organizers have selected CAFA-evaluator as the official CAFA evaluation software. © 2024 The Author(s). Published by Oxford University Press.},
note = {Cited by: 2; All Open Access, Gold Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
We present CAFA-evaluator, a powerful Python program designed to evaluate the performance of prediction methods on targets with hierarchical concept dependencies. It generalizes multi-label evaluation to modern ontologies where the prediction targets are drawn from a directed acyclic graph and achieves high efficiency by leveraging matrix computation and topological sorting. The program requirements include a small number of standard Python libraries, making CAFA-evaluator easy to maintain. The code replicates the Critical Assessment of protein Function Annotation (CAFA) benchmarking, which evaluates predictions of the consistent subgraphs in Gene Ontology. Owing to its reliability and accuracy, the organizers have selected CAFA-evaluator as the official CAFA evaluation software. © 2024 The Author(s). Published by Oxford University Press.
3.
Massimo Bellanda; Milena Damulewicz; Barbara Zambelli; Elisa Costanzi; Francesco Gregoris; Stefano Mammi; Silvio C. E. Tosatto; Rodolfo Costa; Giovanni Minervini; Gabriella M. Mazzotta
A PDZ scaffolding/CaM-mediated pathway in Cryptochrome signaling Journal Article
In: Protein Science, vol. 33, no. 3, 2024, ISSN: 09618368, (Cited by: 0).
@article{Bellanda2024,
title = {A PDZ scaffolding/CaM-mediated pathway in Cryptochrome signaling},
author = { Massimo Bellanda and Milena Damulewicz and Barbara Zambelli and Elisa Costanzi and Francesco Gregoris and Stefano Mammi and Silvio C. E. Tosatto and Rodolfo Costa and Giovanni Minervini and Gabriella M. Mazzotta},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85185346556&doi=10.1002%2fpro.4914&partnerID=40&md5=9d3ca7169c5c85e7e43289adbe2c3e24},
doi = {10.1002/pro.4914},
issn = {09618368},
year = {2024},
date = {2024-01-01},
journal = {Protein Science},
volume = {33},
number = {3},
publisher = {John Wiley and Sons Inc},
abstract = {Cryptochromes are cardinal constituents of the circadian clock, which orchestrates daily physiological rhythms in living organisms. A growing body of evidence points to their participation in pathways that have not traditionally been associated with circadian clock regulation, implying that cryptochromes may be subject to modulation by multiple signaling mechanisms. In this study, we demonstrate that human CRY2 (hCRY2) forms a complex with the large, modular scaffolding protein known as Multi-PDZ Domain Protein 1 (MUPP1). This interaction is facilitated by the calcium-binding protein Calmodulin (CaM) in a calcium-dependent manner. Our findings suggest a novel cooperative mechanism for the regulation of mammalian cryptochromes, mediated by calcium ions (Ca2+) and CaM. We propose that this Ca2+/CaM-mediated signaling pathway may be an evolutionarily conserved mechanism that has been maintained from Drosophila to mammals, most likely in relation to its potential role in the broader context of cryptochrome function and regulation. Further, the understanding of cryptochrome interactions with other proteins and signaling pathways could lead to a better definition of its role within the intricate network of molecular interactions that govern circadian rhythms. © 2024 The Protein Society.},
note = {Cited by: 0},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Cryptochromes are cardinal constituents of the circadian clock, which orchestrates daily physiological rhythms in living organisms. A growing body of evidence points to their participation in pathways that have not traditionally been associated with circadian clock regulation, implying that cryptochromes may be subject to modulation by multiple signaling mechanisms. In this study, we demonstrate that human CRY2 (hCRY2) forms a complex with the large, modular scaffolding protein known as Multi-PDZ Domain Protein 1 (MUPP1). This interaction is facilitated by the calcium-binding protein Calmodulin (CaM) in a calcium-dependent manner. Our findings suggest a novel cooperative mechanism for the regulation of mammalian cryptochromes, mediated by calcium ions (Ca2+) and CaM. We propose that this Ca2+/CaM-mediated signaling pathway may be an evolutionarily conserved mechanism that has been maintained from Drosophila to mammals, most likely in relation to its potential role in the broader context of cryptochrome function and regulation. Further, the understanding of cryptochrome interactions with other proteins and signaling pathways could lead to a better definition of its role within the intricate network of molecular interactions that govern circadian rhythms. © 2024 The Protein Society.
4.
Paula Nazarena Arrías; Zarifa Osmanli; Estefanía Peralta; Patricio Manuel Chinestrad; Alexander Miguel Monzon; Silvio C. E. Tosatto
Diversity and structural-functional insights of alpha-solenoid proteins Journal Article
In: Protein Science, vol. 33, no. 11, 2024, ISSN: 09618368, (Cited by: 0; All Open Access, Hybrid Gold Open Access).
@article{Arrías2024,
title = {Diversity and structural-functional insights of alpha-solenoid proteins},
author = { Paula Nazarena Arrías and Zarifa Osmanli and Estefanía Peralta and Patricio Manuel Chinestrad and Alexander Miguel Monzon and Silvio C. E. Tosatto},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85207813713&doi=10.1002%2fpro.5189&partnerID=40&md5=846b239a4c9a4105e9b257d05a64e1fb},
doi = {10.1002/pro.5189},
issn = {09618368},
year = {2024},
date = {2024-01-01},
journal = {Protein Science},
volume = {33},
number = {11},
publisher = {John Wiley and Sons Inc},
abstract = {Alpha-solenoids are a significant and diverse subset of structured tandem repeat proteins (STRPs) that are important in various domains of life. This review examines their structural and functional diversity and highlights their role in critical cellular processes such as signaling, apoptosis, and transcriptional regulation. Alpha-solenoids can be classified into three geometric folds: low curvature, high curvature, and corkscrew, as well as eight subfolds: ankyrin repeats; Huntingtin, elongation factor 3, protein phosphatase 2A, and target of rapamycin; armadillo repeats; tetratricopeptide repeats; pentatricopeptide repeats; Pumilio repeats; transcription activator-like; and Sel-1 and Sel-1-like repeats. These subfolds represent distinct protein families with unique structural properties and functions, highlighting the versatility of alpha-solenoids. The review also discusses their association with disease, highlighting their potential as therapeutic targets and their role in protein design. Advances in state-of-the-art structure prediction methods provide new opportunities and challenges in the functional characterization and classification of this kind of fold, emphasizing the need for continued development of methods for their identification and proper data curation and deposition in the main databases. © 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.},
note = {Cited by: 0; All Open Access, Hybrid Gold Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
Alpha-solenoids are a significant and diverse subset of structured tandem repeat proteins (STRPs) that are important in various domains of life. This review examines their structural and functional diversity and highlights their role in critical cellular processes such as signaling, apoptosis, and transcriptional regulation. Alpha-solenoids can be classified into three geometric folds: low curvature, high curvature, and corkscrew, as well as eight subfolds: ankyrin repeats; Huntingtin, elongation factor 3, protein phosphatase 2A, and target of rapamycin; armadillo repeats; tetratricopeptide repeats; pentatricopeptide repeats; Pumilio repeats; transcription activator-like; and Sel-1 and Sel-1-like repeats. These subfolds represent distinct protein families with unique structural properties and functions, highlighting the versatility of alpha-solenoids. The review also discusses their association with disease, highlighting their potential as therapeutic targets and their role in protein design. Advances in state-of-the-art structure prediction methods provide new opportunities and challenges in the functional characterization and classification of this kind of fold, emphasizing the need for continued development of methods for their identification and proper data curation and deposition in the main databases. © 2024 The Author(s). Protein Science published by Wiley Periodicals LLC on behalf of The Protein Society.
5.
Francesco Gregoris; Giovanni Minervini; Silvio C. E. Tosatto
In Silico Exploration of AHR-HIF Pathway Interplay: Implications for Therapeutic Targeting in ccRCC Journal Article
In: Genes, vol. 15, no. 9, 2024, ISSN: 20734425, (Cited by: 0; All Open Access, Gold Open Access).
@article{Gregoris2024,
title = {In Silico Exploration of AHR-HIF Pathway Interplay: Implications for Therapeutic Targeting in ccRCC},
author = { Francesco Gregoris and Giovanni Minervini and Silvio C. E. Tosatto},
url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85205114282&doi=10.3390%2fgenes15091167&partnerID=40&md5=4358b236c257d898f6c44e2639ebbd9d},
doi = {10.3390/genes15091167},
issn = {20734425},
year = {2024},
date = {2024-01-01},
journal = {Genes},
volume = {15},
number = {9},
publisher = {Multidisciplinary Digital Publishing Institute (MDPI)},
abstract = {The oxygen-sensing pathway is a crucial regulatory circuit that defines cellular conditions and is extensively exploited in cancer development. Pathogenic mutations in the von Hippel–Lindau (VHL) tumour suppressor impair its role as a master regulator of hypoxia-inducible factors (HIFs), leading to constitutive HIF activation and uncontrolled angiogenesis, increasing the risk of developing clear cell renal cell carcinoma (ccRCC). HIF hyperactivation can sequester HIF-1β, preventing the aryl hydrocarbon receptor (AHR) from correctly activating gene expression in response to endogenous and exogenous ligands such as TCDD (dioxins). In this study, we used protein–protein interaction networks and gene expression profiling to characterize the impact of VHL loss on AHR activity. Our findings reveal specific expression patterns of AHR interactors following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in ccRCC. We identified several AHR interactors significantly associated with poor survival rates in ccRCC patients. Notably, the upregulation of the androgen receptor (AR) and retinoblastoma-associated protein (RB1) by TCDD, coupled with their respective downregulation in ccRCC and association with poor survival rates, suggests novel therapeutic targets. The strategic activation of the AHR via selective AHR modulators (SAhRMs) could stimulate its anticancer activity, specifically targeting RB1 and AR to reduce cell cycle progression and metastasis formation in ccRCC. Our study provides comprehensive insights into the complex interplay between the AHR and HIF pathways in ccRCC pathogenesis, offering novel strategies for targeted therapeutic interventions. © 2024 by the authors.},
note = {Cited by: 0; All Open Access, Gold Open Access},
keywords = {},
pubstate = {published},
tppubtype = {article}
}
The oxygen-sensing pathway is a crucial regulatory circuit that defines cellular conditions and is extensively exploited in cancer development. Pathogenic mutations in the von Hippel–Lindau (VHL) tumour suppressor impair its role as a master regulator of hypoxia-inducible factors (HIFs), leading to constitutive HIF activation and uncontrolled angiogenesis, increasing the risk of developing clear cell renal cell carcinoma (ccRCC). HIF hyperactivation can sequester HIF-1β, preventing the aryl hydrocarbon receptor (AHR) from correctly activating gene expression in response to endogenous and exogenous ligands such as TCDD (dioxins). In this study, we used protein–protein interaction networks and gene expression profiling to characterize the impact of VHL loss on AHR activity. Our findings reveal specific expression patterns of AHR interactors following exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) and in ccRCC. We identified several AHR interactors significantly associated with poor survival rates in ccRCC patients. Notably, the upregulation of the androgen receptor (AR) and retinoblastoma-associated protein (RB1) by TCDD, coupled with their respective downregulation in ccRCC and association with poor survival rates, suggests novel therapeutic targets. The strategic activation of the AHR via selective AHR modulators (SAhRMs) could stimulate its anticancer activity, specifically targeting RB1 and AR to reduce cell cycle progression and metastasis formation in ccRCC. Our study provides comprehensive insights into the complex interplay between the AHR and HIF pathways in ccRCC pathogenesis, offering novel strategies for targeted therapeutic interventions. © 2024 by the authors.