PUBLICATIONS

@article{Piovesan2022144,

title = {Databases for intrinsically disordered proteins},

author = {Damiano Piovesan and Alexander Miguel Monzon and Federica Quaglia and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85123972941\&doi=10.110%2fS2059798321012109\&partnerID=40\&md5=fc97d8245c35d1b0c65faa617398ca2e},

doi = {10.1107/S2059798321012109},

issn = {20597983},

year  = {2022},

date = {2022-01-01},

journal = {Acta Crystallographica Section D: Structural Biology},

volume = {78},

pages = {144 \textendash 151},

publisher = {International Union of Crystallography},

abstract = {Intrinsically disordered regions (IDRs) lacking a fixed three-dimensional protein structure are widespread and play a central role in cell regulation. Only a small fraction of IDRs have been functionally characterized, with heterogeneous experimental evidence that is largely buried in the literature. Predictions of IDRs are still difficult to estimate and are poorly characterized. Here, an overview of the publicly available knowledge about IDRs is reported, including manually curated resources, deposition databases and prediction repositories. The types, scopes and availability of the various resources are analyzed, and their complementarity and overlap are highlighted. The volume of information included and the relevance to the field of structural biology are compared. © 2022.},

note = {Cited by: 8; All Open Access, Green Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Fusto2022,

title = {Expanding the clinical-pathological and genetic spectrum of RYR1-related congenital myopathies with cores and minicores: an Italian population study},

author = {Aurora Fusto and Denise Cassandrini and Chiara Fiorillo and Valentina Codemo and Guja Astrea and Adele D’Amico and Lorenzo Maggi and Francesca Magri and Marika Pane and Giorgio Tasca and Daniele Sabbatini and Luca Bello and Roberta Battini and Pia Bernasconi and Fabiana Fattori and Enrico Silvio Bertini and Giacomo Comi and Sonia Messina and Tiziana Mongini and Isabella Moroni and Chiara Panicucci and Angela Berardinelli and Alice Donati and Vincenzo Nigro and Antonella Pini and Melania Giannotta and Claudia Dosi and Enzo Ricci and Eugenio Mercuri and Giovanni Minervini and Silvio Tosatto and Filippo Santorelli and Claudio Bruno and Elena Pegoraro},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85128316270\&doi=10.118%2fs40478-022-01357-0\&partnerID=40\&md5=f45e114e5bbbb8609c97f49b53b08397},

doi = {10.1186/s40478-022-01357-0},

issn = {20515960},

year  = {2022},

date = {2022-01-01},

journal = {Acta Neuropathologica Communications},

volume = {10},

number = {1},

publisher = {BioMed Central Ltd},

abstract = {Mutations in the RYR1 gene, encoding ryanodine receptor 1 (RyR1), are a well-known cause of Central Core Disease (CCD) and Multi-minicore Disease (MmD). We screened a cohort of 153 patients carrying an histopathological diagnosis of core myopathy (cores and minicores) for RYR1 mutation. At least one RYR1 mutation was identified in 69 of them and these patients were further studied. Clinical and histopathological features were collected. Clinical phenotype was highly heterogeneous ranging from asymptomatic or paucisymptomatic hyperCKemia to severe muscle weakness and skeletal deformity with loss of ambulation. Sixty-eight RYR1 mutations, generally missense, were identified, of which 16 were novel. The combined analysis of the clinical presentation, disease progression and the structural bioinformatic analyses of RYR1 allowed to associate some phenotypes to mutations in specific domains. In addition, this study highlighted the structural bioinformatics potential in the prediction of the pathogenicity of RYR1 mutations. Further improvement in the comprehension of genotype\textendashphenotype relationship of core myopathies can be expected in the next future: the actual lack of the human RyR1 crystal structure paired with the presence of large intrinsically disordered regions in RyR1, and the frequent presence of more than one RYR1 mutation in core myopathy patients, require designing novel investigation strategies to completely address RyR1 mutation effect. © 2022, The Author(s).},

note = {Cited by: 8; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Catoni2022,

title = {Investigating the Retained Inhibitory Effect of Cobimetinib against p.P124L Mutated MEK1: A Combined Liquid Biopsy and in Silico Approach},

author = {Cristina Catoni and Cristina Poggiana and Antonella Facchinetti and Jacopo Pigozzo and Luisa Piccin and Vanna Chiarion-Sileni and Antonio Rosato and Giovanni Minervini and Maria Chiara Scaini},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85137888553\&doi=10.339%2fcancers14174153\&partnerID=40\&md5=97bebd411d8498591f1c8cf1320c09fe},

doi = {10.3390/cancers14174153},

issn = {20726694},

year  = {2022},

date = {2022-01-01},

journal = {Cancers},

volume = {14},

number = {17},

publisher = {MDPI},

abstract = {The systemic treatment of metastatic melanoma has radically changed, due to an improvement in the understanding of its genetic landscape and the advent of targeted therapy. However, the response to BRAF/MEK inhibitors is transitory, and big efforts were made to identify the mechanisms underlying the resistance. We exploited a combined approach, encompassing liquid biopsy analysis and molecular dynamics simulation, for tracking tumor evolution, and in parallel defining the best treatment option. The samples at different time points were collected from a BRAF-mutant melanoma patient who developed an early resistance to dabrafenib/trametinib. The analysis of the circulating tumor DNA (ctDNA) identified the MEK1 p.P124L mutation that confers resistance to trametinib. With an in silico modeling, we identified cobimetinib as an alternative MEK inhibitor, and consequently suggested a therapy switch to vemurafenib/cobimetinib. The patient response was followed by ctDNA tracking and circulating melanoma cell (CMC) count. The cobimetinib administration led to an important reduction in the BRAF p.V600E and MEK1 p.P124L allele fractions and in the CMC number, features suggestive of a putative response. In summary, this study emphasizes the usefulness of a liquid biopsy-based approach combined with in silico simulation, to track real-time tumor evolution while assessing the best treatment option. © 2022 by the authors.},

note = {Cited by: 4; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Varadi2022,

title = {3D-Beacons: Decreasing the gap between protein sequences and structures through a federated network of protein structure data resources},

author = {Mihaly Varadi and Sreenath Nair and Ian Sillitoe and Gerardo Tauriello and Stephen Anyango and Stefan Bienert and Clemente Borges and Mandar Deshpande and Tim Green and Demis Hassabis and Andras Hatos and Tamas Hegedus and Maarten L Hekkelman and Robbie Joosten and John Jumper and Agata Laydon and Dmitry Molodenskiy and Damiano Piovesan and Edoardo Salladini and Steven L Salzberg and Markus J Sommer and Martin Steinegger and Erzsebet Suhajda and Dmitri Svergun and Luiggi Tenorio-Ku and Silvio Tosatto and Kathryn Tunyasuvunakool and Andrew Mark Waterhouse and Augustin Z\'{i}dek and Torsten Schwede and Christine Orengo and Sameer Velankar},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85143181019\&doi=10.109%2fgigascienc%2fgiac118\&partnerID=40\&md5=dfed4704c49e7d2e74567a6f836f6dad},

doi = {10.1093/gigascience/giac118},

issn = {2047217X},

year  = {2022},

date = {2022-01-01},

journal = {GigaScience},

volume = {11},

publisher = {Oxford University Press},

abstract = {While scientists can often infer the biological function of proteins from their 3-dimensional quaternary structures, the gap between the number of known protein sequences and their experimentally determined structures keeps increasing. A potential solution to this problem is presented by ever more sophisticated computational protein modeling approaches. While often powerful on their own, most methods have strengths and weaknesses. Therefore, it benefits researchers to examine models from various model providers and perform comparative analysis to identify what models can best address their specific use cases. To make data from a large array of model providers more easily accessible to the broader scientific community, we established 3D-Beacons, a collaborative initiative to create a federated network with unified data access mechanisms. The 3D-Beacons Network allows researchers to collate coordinate files and metadata for experimentally determined and theoretical protein models from state-of-The-Art and specialist model providers and also from the Protein Data Bank. © 2022 The Author(s). Published by Oxford University Press GigaScience.},

note = {Cited by: 13; All Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Peronato2021130,

title = {New data on c1qdc from the colonial ascidian botryllus schlosseri},

author = {A. Peronato and G. Minervini and N. Franchi and Loriano Ballarin},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85118615793\&doi=10.2543%2f1824-307%2fisj.v18i1.130-137\&partnerID=40\&md5=bdf4a7a1e0386e2f75ff2d963fd22850},

doi = {10.25431/1824-307X/isj.v18i1.130-137},

issn = {1824307X},

year  = {2021},

date = {2021-01-01},

journal = {Invertebrate Survival Journal},

volume = {18},

number = {1},

pages = {130 \textendash 137},

publisher = {Universita degli Studi di Modena e Reggio Emilia},

abstract = {In the compound ascidian Botryllus schlosseri, we recently identified a novel C1q-domain-containing (C1qDC) protein expressed by circulating immunocytes, called BsC1qDC. It has two globular C1q domains and a signal peptide and can act either as an opsonin and facilitate the phagocytosis of nonself particles or as a cytokine and stimulate the degranulation of cytotoxic cells. In the present work, we used a commercial antibody raised against human CTRP4 (hCTRP4) to provide additional evidences of the involvement of this molecule in immune responses. The antibody was validated in immunoblot analysis and recognizes a band corresponding to the expected molecular weight inferred from the analysis of the amino acid sequence of BsC1qDC. The presence of the antibody in the culture medium in phagocytosis and degranulation assays significantly reduced the two responses. In addition, the relationships between complement C3 activation and bsc1qdc transcription was studied using the injection of C3aR agonist in the colonial vasculature. © 2021, Universita degli Studi di Modena e Reggio Emilia. All rights reserved.},

note = {Cited by: 1},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Dassie2021732,

title = {Neurocognitive assessment and DNA sequencing expand the phenotype and genotype spectrum of Alstr\"{o}m syndrome},

author = {Francesca Dassie and Riccardina Lorusso and Silvia Benavides-Varela and Gabriella Milan and Francesca Favaretto and Edward Callus and Stefano Cagnin and Francesco Reggiani and Giovanni Minervini and Silvio Tosatto and Roberto Vettor and Carlo Semenza and Pietro Maffei},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099072292\&doi=10.100%2fajmg.a.62029\&partnerID=40\&md5=90f9ce8208169184e4f97ee183a204b6},

doi = {10.1002/ajmg.a.62029},

issn = {15524825},

year  = {2021},

date = {2021-01-01},

journal = {American Journal of Medical Genetics, Part A},

volume = {185},

number = {3},

pages = {732 \textendash 742},

publisher = {John Wiley and Sons Inc},

abstract = {Alstr\"{o}m syndrome (OMI#203800) is an ultra-rare autosomal recessive monogenic disease presenting pathogenic variants in ALMS1 (chromosome 2p13). It is characterized by early onset of blindness, hearing loss and systemic comorbidities, with delayed development without cognitive impairment. We aimed to investigate the cognitive functions and describe new pathogenic variants in Alstr\"{o}m syndrome patients. Nineteen patients (13 adults, 6 children) underwent a thorough clinical, genetic, laboratory, instrumental, and neurocognitive assessment. Six new pathogenic variants in ALMS1 including the first described in exon 6 were identified. Four patients displayed a “mild phenotype” characterized by slow disease onset or absence of complications, including childhood obesity and association with at least one pathogenic variant in exon 5 or 6. At neurocognitive testing, a significant proportion of patients had deficits in three neurocognitive domains: similarities, phonological memory, and apraxia. In particular, 5% of patients showed difficulties in the auditory working memory test. We found ideomotor and buccofacial apraxia in 7% of patients. “Mild phenotype” patients performed better on auditory working memory and ideomotor apraxia test than “typical phenotype” ones (91.9 + 16.% vs. 41.7 + 34.% of correct answers},

note = {Cited by: 5},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ciaccio2021484,

title = {A Missense de Novo Variant in the CASK -interactor KIRREL3 Gene Leading to Neurodevelopmental Disorder with Mild Cerebellar Hypoplasia},

author = {Claudia Ciaccio and Emanuela Leonardi and Roberta Polli and Alessandra Murgia and Stefano D'Arrigo and Elisa Granocchio and Luisa Chiapparini and Chiara Pantaleoni and Silvia Esposito},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85104381200\&doi=10.105%2fs-0041-1725964\&partnerID=40\&md5=cc224c7e211e9b88045f92d2f23228ec},

doi = {10.1055/s-0041-1725964},

issn = {0174304X},

year  = {2021},

date = {2021-01-01},

journal = {Neuropediatrics},

volume = {52},

number = {6},

pages = {484 \textendash 488},

publisher = {Georg Thieme Verlag},

abstract = {KIRREL3 is a gene important for the central nervous system development-in particular for the process of neuronal migration, axonal fasciculation, and synaptogenesis-and colocalizes and cooperates in neurons with CASK gene. Alterations of KIRREL3 have been linked to neurodevelopmental disorders, ranging from developmental delay, to autism spectrum disorder, to attention deficit/hyperactivity disorder. The underlying mechanism is not yet fully understood, as it has been hypothesized a fully dominant effect, a risk factor role of KIRREL3 partially penetrating variants, and a recessive inheritance pattern. We report a novel and de novo KIRREL3 mutation in a child affected by severe neurodevelopmental disorder and with brain magnetic resonance imaging evidence of mega cisterna magna and mild cerebellar hypoplasia. This case strengthens the hypothesis that dominant KIRREL3 variants may lead to neurodevelopmental disruption; furthermore, given the strong interaction between KIRREL3 and CASK, we discuss as posterior fossa anomalies may also be part of the phenotype of KIRREL3 -related syndrome. © 2021 Georg Thieme Verlag. All rights reserved.},

note = {Cited by: 4},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Bertolio2021,

title = {A Novel Splice Variant of Human TGF-β Type II Receptor Encodes a Soluble Protein and Its Fc-Tagged Version Prevents Liver Fibrosis in vivo},

author = {Marcela Soledad Bertolio and Anabela La Colla and Alejandra Carrea and Ana Romo and Gabriela Canziani and Stella Maris Echarte and Sabrina Campisano and German Patricio Barletta and Alexander Miguel Monzon and Tania Melina Rodr\'{i}guez and Andrea Nancy Chisari and Ricardo Alfredo Dewey},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85115828696\&doi=10.338%2ffcell.2021.690397\&partnerID=40\&md5=26e5f138dcc93d1195f8a2ee8232f853},

doi = {10.3389/fcell.2021.690397},

issn = {2296634X},

year  = {2021},

date = {2021-01-01},

journal = {Frontiers in Cell and Developmental Biology},

volume = {9},

publisher = {Frontiers Media S.A.},

abstract = {We describe, for the first time, a new splice variant of the human TGF-β type II receptor (TβRII). The new transcript lacks 149 nucleotides, resulting in a frameshift and the emergence of an early stop codon, rendering a truncated mature protein of 57 amino acids. The predicted protein, lacking the transmembrane domain and with a distinctive 13-amino-acid stretch at its C-terminus, was named TβRII-Soluble Endogenous (TβRII-SE). Binding predictions indicate that the novel 13-amino-acid stretch interacts with all three TGF-β cognate ligands and generates a more extensive protein\textendashprotein interface than TβRII. TβRII-SE and human IgG1 Fc domain were fused in frame in a lentiviral vector (Lv) for further characterization. With this vector, we transduced 293T cells and purified TβRII-SE/Fc by A/G protein chromatography from conditioned medium. Immunoblotting revealed homogeneous bands of approximately 37 kDa (reduced) and 75 kDa (non-reduced), indicating that TβRII-SE/Fc is secreted as a disulfide-linked homodimer. Moreover, high-affinity binding of TβRII-SE to the three TGF-β isoforms was confirmed by surface plasmon resonance (SPR) analysis. Also, intrahepatic delivery of Lv.TβRII-SE/Fc in a carbon tetrachloride-induced liver fibrosis model revealed amelioration of liver injury and fibrosis. Our results indicate that TβRII-SE is a novel member of the TGF-β signaling pathway with distinctive characteristics. This novel protein offers an alternative for the prevention and treatment of pathologies caused by the overproduction of TGF-β ligands. © Copyright © 2021 Bertolio, La Colla, Carrea, Romo, Canziani, Echarte, Campisano, Barletta, Monzon, Rodr\'{i}guez, Chisari and Dewey.},

note = {Cited by: 2; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Parisi2021146,

title = {“Protein” no longer means what it used to},

author = {Gustavo Parisi and Nicolas Palopoli and Silvio C. E. Tosatto and Mar\'{i}a Silvina Fornasari and Peter Tompa},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85110173062\&doi=10.101%2fj.crstbi.2021.06.002\&partnerID=40\&md5=321e4bde0899a3591a6fa727f8d97700},

doi = {10.1016/j.crstbi.2021.06.002},

issn = {2665928X},

year  = {2021},

date = {2021-01-01},

journal = {Current Research in Structural Biology},

volume = {3},

pages = {146 \textendash 152},

publisher = {Elsevier B.V.},

abstract = {Every biologist knows that the word protein describes a group of macromolecules essential to sustain life on Earth. As biologists, we are invariably trained under a protein paradigm established since the early twentieth century. However, in recent years, the term protein unveiled itself as an euphemism to describe the overwhelming heterogeneity of these compounds. Most of our current studies are targeted on carefully selected subsets of proteins, but we tend to think and write about these as representative of the whole population. Here we discuss how seeking for universal definitions and general rules in any arbitrarily segmented study would be misleading about the conclusions. Of course, it is not our purpose to discourage the use of the word protein. Instead, we suggest to embrace the extended universe of proteins to reach a deeper understanding of their full potential, realizing that the term encompasses a group of molecules very heterogeneous in terms of size, shape, chemistry and functions, i.e. the term protein no longer means what it used to. © 2021 The Authors},

note = {Cited by: 2; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Palopoli2021,

title = {Intrinsically Disordered Protein Ensembles Shape Evolutionary Rates Revealing Conformational Patterns},

author = {Nicolas Palopoli and Julia Marchetti and Alexander M. Monzon and Diego J. Zea and Silvio C. E. Tosatto and Maria S. Fornasari and Gustavo Parisi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098132673\&doi=10.101%2fj.jmb.2020.166751\&partnerID=40\&md5=4ca93b56c7035b46d6e54336f45045da},

doi = {10.1016/j.jmb.2020.166751},

issn = {00222836},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Molecular Biology},

volume = {433},

number = {3},

publisher = {Academic Press},

abstract = {Intrinsically disordered proteins (IDPs) lack stable tertiary structure under physiological conditions. The unique composition and complex dynamical behaviour of IDPs make them a challenge for structural biology and molecular evolution studies. Using NMR ensembles, we found that IDPs evolve under a strong site-specific evolutionary rate heterogeneity, mainly originated by different constraints derived from their inter-residue contacts. Evolutionary rate profiles correlate with the experimentally observed conformational diversity of the protein, allowing the description of different conformational patterns possibly related to their structure-function relationships. The correlation between evolutionary rates and contact information improves when structural information is taken not from any individual conformer or the whole ensemble, but from combining a limited number of conformers. Our results suggest that residue contacts in disordered regions constrain evolutionary rates to conserve the dynamic behaviour of the ensemble and that evolutionary rates can be used as a proxy for the conformational diversity of IDPs. © 2020 Elsevier Ltd},

note = {Cited by: 3; All Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Walsh20211122,

title = {DOME: recommendations for supervised machine learning validation in biology},

author = {Ian Walsh and Dmytro Fishman and Dario Garcia-Gasulla and Tiina Titma and Gianluca Pollastri and Emidio Capriotti and Rita Casadio and Salvador Capella-Gutierrez and Davide Cirillo and Alessio Del Conte and Alexandros C. Dimopoulos and Victoria Dominguez Del Angel and Joaquin Dopazo and Piero Fariselli and Jos\'{e} Maria Fern\'{a}ndez and Florian Huber and Anna Kreshuk and Tom Lenaerts and Pier Luigi Martelli and Arcadi Navarro and Pilib \'{O} Broin and Janet Pi\~{n}ero and Damiano Piovesan and Martin Reczko and Francesco Ronzano and Venkata Satagopam and Castrense Savojardo and Vojtech Spiwok and Marco Antonio Tangaro and Giacomo Tartari and David Salgado and Alfonso Valencia and Federico Zambelli and Jennifer Harrow and Fotis E. Psomopoulos and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85111967406\&doi=10.103%2fs41592-021-01205-4\&partnerID=40\&md5=7d42fbefbd36a1f5502de4566a1f17f8},

doi = {10.1038/s41592-021-01205-4},

issn = {15487091},

year  = {2021},

date = {2021-01-01},

journal = {Nature Methods},

volume = {18},

number = {10},

pages = {1122 \textendash 1127},

publisher = {Nature Research},

note = {Cited by: 126; All Open Access, Bronze Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Blum2021D344,

title = {The InterPro protein families and domains database: 20 years on},

author = {Matthias Blum and Hsin-Yu Chang and Sara Chuguransky and Tiago Grego and Swaathi Kandasaamy and Alex Mitchell and Gift Nuka and Typhaine Paysan-Lafosse and Matloob Qureshi and Shriya Raj and Lorna Richardson and Gustavo A. Salazar and Lowri Williams and Peer Bork and Alan Bridge and Julian Gough and Daniel H. Haft and Ivica Letunic and Aron Marchler-Bauer and Huaiyu Mi and Darren A. Natale and Marco Necci and Christine A. Orengo and Arun P. Pandurangan and Catherine Rivoire and Christian J. A. Sigrist and Ian Sillitoe and Narmada Thanki and Paul D. Thomas and Silvio C. E. Tosatto and Cathy H. Wu and Alex Bateman and Robert D. Finn},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099149539\&doi=10.109%2fna%2fgkaa977\&partnerID=40\&md5=ec953cbde877f7bb90027b61a5e2df9e},

doi = {10.1093/nar/gkaa977},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {D1},

pages = {D344 \textendash D354},

publisher = {Oxford University Press},

abstract = {The InterPro database (https://www.ebi.ac.uk/interpro/) provides an integrative classification of protein sequences into families, and identifies functionally important domains and conserved sites. InterProScan is the underlying software that allows protein and nucleic acid sequences to be searched against InterPro's signatures. Signatures are predictive models which describe protein families, domains or sites, and are provided by multiple databases. InterPro combines signatures representing equivalent families, domains or sites, and provides additional information such as descriptions, literature references and Gene Ontology (GO) terms, to produce a comprehensive resource for protein classification. Founded in 1999, InterPro has become one of the most widely used resources for protein family annotation. Here, we report the status of InterPro (version 81.0) in its 20th year of operation and its associated software, including updates to database content, the release of a new website and REST API, and performance improvements in InterProScan. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.},

note = {Cited by: 1270; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hatos2021,

title = {APICURON: A database to credit and acknowledge the work of biocurators},

author = {Andr\'{a}s Hatos and Federica Quaglia and Damiano Piovesan and Silvio C. E Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105906122\&doi=10.109%2fdatabas%2fbaab019\&partnerID=40\&md5=9261770789a1898e282c359c43487109},

doi = {10.1093/database/baab019},

issn = {17580463},

year  = {2021},

date = {2021-01-01},

journal = {Database},

volume = {2021},

publisher = {Oxford University Press},

abstract = {APICURON is an open and freely accessible resource that tracks and credits the work of biocurators across multiple participating knowledgebases. Biocuration is essential to extract knowledge from research data and make it available in a structured and standardized way to the scientific community. However, processing biological data - mainly from literature - requires a huge effort that is difficult to attribute and quantify. APICURON collects biocuration events from third-party resources and aggregates this information, spotlighting biocurator contributions. APICURON promotes biocurator engagement implementing gamification concepts like badges, medals and leaderboards and at the same time provides a monitoring service for registered resources and for biocurators themselves. APICURON adopts a data model that is flexible enough to represent and track the majority of biocuration activities. Biocurators are identified through their Open Researcher and Contributor ID. The definition of curation events, scoring systems and rules for assigning badges and medals are resource-specific and easily customizable. Registered resources can transfer curation activities on the fly through a secure and robust Application Programming Interface (API). Here, we show how simple and effective it is to connect a resource to APICURON, describing the DisProt database of intrinsically disordered proteins as a use case. We believe APICURON will provide biological knowledgebases with a service to recognize and credit the effort of their biocurators, monitor their activity and promote curator engagement. Database URL: https://apicuron.org © 2021 The Author(s). Published by Oxford University Press.},

note = {Cited by: 9; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Paladin2021D452,

title = {RepeatsDB in 2021: Improved data and extended classification for protein tandem repeat structures},

author = {Lisanna Paladin and Martina Bevilacqua and Sara Errigo and Damiano Piovesan and Ivan Mi\v{c}eti\'{c} and Marco Necci and Alexander Miguel Monzon and Maria Laura Fabre and Jose Luis Lopez and Juliet F. Nilsson and Javier Rios and Pablo Lorenzano Menna and Maia Cabrera and Martin Gonzalez Buitron and Mariane Gon\c{c}alves Kulik and Sebastian Fernandez-Alberti and Maria Silvina Fornasari and Gustavo Parisi and Antonio Lagares and Layla Hirsh and Miguel A. Andrade-Navarro and Andrey V. Kajava and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099429028\&doi=10.109%2fna%2fgkaa1097\&partnerID=40\&md5=9a76417ee8612b9b07dd285c326e9b92},

doi = {10.1093/nar/gkaa1097},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {D1},

pages = {D452 \textendash D457},

publisher = {Oxford University Press},

abstract = {The RepeatsDB database (URL: https://repeatsdb.org/) provides annotations and classification for protein tandem repeat structures from the Protein Data Bank (PDB). Protein tandem repeats are ubiquitous in all branches of the tree of life. The accumulation of solved repeat structures provides new possibilities for classification and detection, but also increasing the need for annotation. Here we present RepeatsDB 3.0, which addresses these challenges and presents an extended classification scheme. The major conceptual change compared to the previous version is the hierarchical classification combining top levels based solely on structural similarity (Class \> Topology \> Fold) with two new levels (Clan \> Family) requiring sequence similarity and describing repeat motifs in collaboration with Pfam. Data growth has been addressed with improved mechanisms for browsing the classification hierarchy. A new UniProt-centric view unifies the increasingly frequent annotation of structures from identical or similar sequences. This update of RepeatsDB aligns with our commitment to develop a resource that extracts, organizes and distributes specialized information on tandem repeat protein structures. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 31; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quaglia2021,

title = {Exploring Curated Conformational Ensembles of Intrinsically Disordered Proteins in the Protein Ensemble Database},

author = {Federica Quaglia and Tamas Lazar and Andr\'{a}s Hatos and Peter Tompa and Damiano Piovesan and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85111647557\&doi=10.100%2fcpz1.192\&partnerID=40\&md5=53d4b56ebbb5608634b54a78006c8acb},

doi = {10.1002/cpz1.192},

issn = {26911299},

year  = {2021},

date = {2021-01-01},

journal = {Current Protocols},

volume = {1},

number = {7},

publisher = {John Wiley and Sons Inc},

abstract = {The Protein Ensemble Database (PED; https://proteinensemble.org/) is the major repository of conformational ensembles of intrinsically disordered proteins (IDPs). Conformational ensembles of IDPs are primarily provided by their authors or occasionally collected from literature, and are subsequently deposited in PED along with the corresponding structured, manually curated metadata. The modeling of conformational ensembles usually relies on experimental data from small-angle X-ray scattering (SAXS), fluorescence resonance energy transfer (FRET), NMR spectroscopy, and molecular dynamics (MD) simulations, or a combination of these techniques. The growing number of scientific studies based on these data, along with the astounding and swift progress in the field of protein intrinsic disorder, has required a significant update and upgrade of PED, first published in 2014. To this end, the database was entirely renewed in 2020 and now has a dedicated team of biocurators providing manually curated descriptions of the methods and conditions applied to generate the conformational ensembles and for checking consistency of the data. Here, we present a detailed description on how to explore PED with its protein pages and experimental pages, and how to interpret entries of conformational ensembles. We describe how to efficiently search conformational ensembles deposited in PED by means of its web interface and API. We demonstrate how to make sense of the PED protein page and its associated experimental entry pages with reference to the yeast Sic1 use case. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Performing a search in PED. Support Protocol 1: Programmatic access with the PED API. Basic Protocol 2: Interpreting the protein page and the experimental entry page\textemdashthe Sic1 use case. Support Protocol 2: Downloading options. Support Protocol 3: Understanding the validation report\textemdashthe Sic1 use case. Basic Protocol 3: Submitting new conformational ensembles to PED. Basic Protocol 4: Providing feedback in PED. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC.},

note = {Cited by: 4; All Open Access, Green Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Monzon2021,

title = {FLIPPER: Predicting and Characterizing Linear Interacting Peptides in the Protein Data Bank},

author = {Alexander Miguel Monzon and Paolo Bonato and Marco Necci and Silvio C. E. Tosatto and Damiano Piovesan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85102363042\&doi=10.101%2fj.jmb.2021.166900\&partnerID=40\&md5=8970e16f480a6c9b7822e5eeda13dbaa},

doi = {10.1016/j.jmb.2021.166900},

issn = {00222836},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Molecular Biology},

volume = {433},

number = {9},

publisher = {Academic Press},

abstract = {A large fraction of peptides or protein regions are disordered in isolation and fold upon binding. These regions, also called MoRFs, SLiMs or LIPs, are often associated with signaling and regulation processes. However, despite their importance, only a limited number of examples are available in public databases and their automatic detection at the proteome level is problematic. Here we present FLIPPER, an automatic method for the detection of structurally linear sub-regions or peptides that interact with another chain in a protein complex. FLIPPER is a random forest classification that takes the protein structure as input and provides the propensity of each amino acid to be part of a LIP region. Models are built taking into consideration structural features such as intra- and inter-chain contacts, secondary structure, solvent accessibility in both bound and unbound state, structural linearity and chain length. FLIPPER is accurate when evaluated on non-redundant independent datasets, 9% precision and 9% sensitivity on PixelDB-25 and 8% precision and 8% sensitivity on DIBS-25. Finally, we used FLIPPER to process the entire Protein Data Bank and identified different classes of LIPs based on different binding modes and partner molecules. We provide a detailed description of these LIP categories and show that a large fraction of these regions are not detected by disorder predictors. All FLIPPER predictions are integrated in the MobiDB 4.0 database. © 2021 Elsevier Ltd},

note = {Cited by: 9; All Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Laquatra2021,

title = {HIF1α-dependent induction of the mitochondrial chaperone TRAP1 regulates bioenergetic adaptations to hypoxia},

author = {Claudio Laquatra and Carlos Sanchez-Martin and Alberto Dinarello and Giuseppe Cannino and Giovanni Minervini and Elisabetta Moroni and Marco Schiavone and Silvio Tosatto and Francesco Argenton and Giorgio Colombo and Paolo Bernardi and Ionica Masgras and Andrea Rasola},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105148823\&doi=10.103%2fs41419-021-03716-6\&partnerID=40\&md5=ae8179c901d3fff15773d658be7669de},

doi = {10.1038/s41419-021-03716-6},

issn = {20414889},

year  = {2021},

date = {2021-01-01},

journal = {Cell Death and Disease},

volume = {12},

number = {5},

publisher = {Springer Nature},

abstract = {The mitochondrial paralog of the Hsp90 chaperone family TRAP1 is often induced in tumors, but the mechanisms controlling its expression, as well as its physiological functions remain poorly understood. Here, we find that TRAP1 is highly expressed in the early stages of Zebrafish development, and its ablation delays embryogenesis while increasing mitochondrial respiration of fish larvae. TRAP1 expression is enhanced by hypoxic conditions both in developing embryos and in cancer models of Zebrafish and mammals. The TRAP1 promoter contains evolutionary conserved hypoxic responsive elements, and HIF1α stabilization increases TRAP1 levels. TRAP1 inhibition by selective compounds or by genetic knock-out maintains a high level of respiration in Zebrafish embryos after exposure to hypoxia. Our data identify TRAP1 as a primary regulator of mitochondrial bioenergetics in highly proliferating cells following reduction in oxygen tension and HIF1α stabilization. © 2021, The Author(s).},

note = {Cited by: 19; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Galber2021,

title = {The f subunit of human ATP synthase is essential for normal mitochondrial morphology and permeability transition},

author = {Chiara Galber and Giovanni Minervini and Giuseppe Cannino and Francesco Boldrin and Valeria Petronilli and Silvio Tosatto and Giovanna Lippe and Valentina Giorgio},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105603447\&doi=10.101%2fj.celrep.2021.109111\&partnerID=40\&md5=6c60fcdbcffbd3acc8f253ed141569fa},

doi = {10.1016/j.celrep.2021.109111},

issn = {22111247},

year  = {2021},

date = {2021-01-01},

journal = {Cell Reports},

volume = {35},

number = {6},

publisher = {Elsevier B.V.},

abstract = {The f subunit is localized at the base of the ATP synthase peripheral stalk. Its function in the human enzyme is poorly characterized. Because full disruption of its ATP5J2 gene with the CRISPR-Cas9 strategy in the HAP1 human model has been shown to cause alterations in the amounts of other ATP synthase subunits, here we investigated the role of the f subunit in HeLa cells by regulating its levels through RNA interference. We confirm the role of the f subunit in ATP synthase dimer stability and observe that its downregulation per se does not alter the amounts of the other enzyme subunits or ATP synthase synthetic/hydrolytic activity. We show that downregulation of the f subunit causes abnormal crista organization and decreases permeability transition pore (PTP) size, whereas its re-expression in f subunit knockdown cells rescues mitochondrial morphology and PTP-dependent swelling. © 2021 The Authors},

note = {Cited by: 26; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Peronato2021,

title = {Characterisation and functional role of a novel C1qDC protein from a colonial ascidian},

author = {A. Peronato and G. Minervini and M. Tabarelli and L. Ballarin and N. Franchi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85105251462\&doi=10.101%2fj.dci.2021.104077\&partnerID=40\&md5=18bd3941006541963cb5078c6f76bcc0},

doi = {10.1016/j.dci.2021.104077},

issn = {0145305X},

year  = {2021},

date = {2021-01-01},

journal = {Developmental and Comparative Immunology},

volume = {122},

publisher = {Elsevier Ltd},

abstract = {As an invertebrate, the compound ascidian Botryllus schlosseri faces nonself only with innate immunity. In this species, we already identified the key components of the lectin and alternative complement activation pathways. In the present work, by mining the transcriptome, we identified a single transcript codifying for a protein, member of the C1q-domain-containing protein family, with a signal peptide followed by two globular C1q (gC1q) domains. It shares a similar domain organisation with C1q/TNF-related proteins 4, the only vertebrate protein family with two gC1q domains. Our gC1q domain-containing protein, called BsC1qDC, is actively transcribed by immunocytes. The transcription is modulated during the Botryllus blastogenetic cycle and is upregulated following the injection of Bacillus clausii cells in the circulation. Furthermore, the injection of bsc1qdc iRNA in the vasculature results in decreased transcription of the gene and a significant impairment of phagocytosis and degranulation, suggesting the involvement of this molecule in immune responses. © 2021 Elsevier Ltd},

note = {Cited by: 6},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Necci2021472,

title = {Critical assessment of protein intrinsic disorder prediction},

author = {Marco Necci and Damiano Piovesan and Md Tamjidul Hoque and Ian Walsh and Sumaiya Iqbal and Michele Vendruscolo and Pietro Sormanni and Chen Wang and Daniele Raimondi and Ronesh Sharma and Yaoqi Zhou and Thomas Litfin and Oxana Valerianovna Galzitskaya and Michail Yu. Lobanov and Wim Vranken and Bj\"{o}rn Wallner and Claudio Mirabello and Nawar Malhis and Zsuzsanna Doszt\'{a}nyi and G\'{a}bor Erd\H{o}s and B\'{a}lint M\'{e}sz\'{a}ros and Jianzhao Gao and Kui Wang and Gang Hu and Zhonghua Wu and Alok Sharma and Jack Hanson and Kuldip Paliwal and Isabelle Callebaut and Tristan Bitard-Feildel and Gabriele Orlando and Zhenling Peng and Jinbo Xu and Sheng Wang and David T. Jones and Domenico Cozzetto and Fanchi Meng and Jing Yan and J\"{o}rg Gsponer and Jianlin Cheng and Tianqi Wu and Lukasz Kurgan and Vasilis J. Promponas and Stella Tamana and Cristina Marino-Buslje and Elizabeth Mart\'{i}nez-P\'{e}rez and Anastasia Chasapi and Christos Ouzounis and A. Keith Dunker and Andrey V. Kajava and Jeremy Y. Leclercq and Burcu Aykac-Fas and Matteo Lambrughi and Emiliano Maiani and Elena Papaleo and Lucia Beatriz Chemes and Luc\'{i}a \'{A}lvarez and Nicol\'{a}s S. Gonz\'{a}lez-Foutel and Valentin Iglesias and Jordi Pujols and Salvador Ventura and Nicol\'{a}s Palopoli and Guillermo Ignacio Ben\'{i}tez and Gustavo Parisi and Claudio Bassot and Arne Elofsson and Sudha Govindarajan and John Lamb and Marco Salvatore and Andr\'{a}s Hatos and Alexander Miguel Monzon and Martina Bevilacqua and Ivan Mi\v{c}eti\'{c} and Giovanni Minervini and Lisanna Paladin and Federica Quaglia and Emanuela Leonardi and Norman Davey and Tamas Horvath and Orsolya Panna Kovacs and Nikoletta Murvai and Rita Pancsa and Eva Schad and Beata Szabo and Agnes Tantos and Sandra Macedo-Ribeiro and Jose Antonio Manso and Pedro Jos\'{e} Barbosa Pereira and Radoslav Davidovi\'{c} and Nevena Veljkovic and Borb\'{a}la Hajdu-Solt\'{e}sz and M\'{a}ty\'{a}s Pajkos and Tam\'{a}s Szaniszl\'{o} and Mainak Guharoy and Tamas Lazar and Mauricio Macossay-Castillo and Peter Tompa and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85104988931\&doi=10.103%2fs41592-021-01117-3\&partnerID=40\&md5=de0effc341a3dba548f76a749640b858},

doi = {10.1038/s41592-021-01117-3},

issn = {15487091},

year  = {2021},

date = {2021-01-01},

journal = {Nature Methods},

volume = {18},

number = {5},

pages = {472 \textendash 481},

publisher = {Nature Research},

abstract = {Intrinsically disordered proteins, defying the traditional protein structure\textendashfunction paradigm, are a challenge to study experimentally. Because a large part of our knowledge rests on computational predictions, it is crucial that their accuracy is high. The Critical Assessment of protein Intrinsic Disorder prediction (CAID) experiment was established as a community-based blind test to determine the state of the art in prediction of intrinsically disordered regions and the subset of residues involved in binding. A total of 43 methods were evaluated on a dataset of 646 proteins from DisProt. The best methods use deep learning techniques and notably outperform physicochemical methods. The top disorder predictor has Fmax = 0.483 on the full dataset and Fmax = 0.792 following filtering out of bona fide structured regions. Disordered binding regions remain hard to predict, with Fmax = 0.231. Interestingly, computing times among methods can vary by up to four orders of magnitude. © 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.},

note = {Cited by: 185; All Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Lazar2021D404,

title = {PED in 2021: A major update of the protein ensemble database for intrinsically disordered proteins},

author = {Tamas Lazar and Elizabeth Mart\'{i}nez-P\'{e}rez and Federica Quaglia and Andr\'{a}s Hatos and Luc\'{i}a B. Chemes and Javier A. Iserte and Nicol\'{a}s A. M\'{e}ndez and Nicol\'{a}s A. Garrone and Tadeo E. Salda\~{n}o and Julia Marchetti and Ana Julia Velez Rueda and Pau Bernad\'{o} and Martin Blackledge and Tiago N. Cordeiro and Eric Fagerberg and Julie D. Forman-Kay and Maria S. Fornasari and Toby J. Gibson and Gregory-Neal W. Gomes and Claudiu C. Gradinaru and Teresa Head-Gordon and Malene Ringkj\obing Jensen and Edward A. Lemke and Sonia Longhi and Cristina Marino-Buslje and Giovanni Minervini and Tanja Mittag and Alexander Miguel Monzon and Rohit V. Pappu and Gustavo Parisi and Sylvie Ricard-Blum and Kiersten M. Ruff and Edoardo Salladini and Marie Skep\"{o} and Dmitri Svergun and Sylvain D. Vallet and Mihaly Varadi and Peter Tompa and Silvio C. E. Tosatto and Damiano Piovesan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85095859724\&doi=10.109%2fna%2fgkaa1021\&partnerID=40\&md5=6f8bf0f0f08b4ca4c47029b9da1f5ac7},

doi = {10.1093/nar/gkaa1021},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {D1},

pages = {D404 \textendash D411},

publisher = {Oxford University Press},

abstract = {The Protein Ensemble Database (PED) (https://proteinensemble.org), which holds structural ensembles of intrinsically disordered proteins (IDPs), has been significantly updated and upgraded since its last release in 2016. The new version, PED 4.0, has been completely redesigned and reimplemented with cutting-edge technology and now holds about six times more data (162 versus 24 entries and 242 versus 60 structural ensembles) and a broader representation of state of the art ensemble generation methods than the previous version. The database has a completely renewed graphical interface with an interactive feature viewer for region-based annotations, and provides a series of descriptors of the qualitative and quantitative properties of the ensembles. High quality of the data is guaranteed by a new submission process, which combines both automatic and manual evaluation steps. A team of biocurators integrate structured metadata describing the ensemble generation methodology, experimental constraints and conditions. A new search engine allows the user to build advanced queries and search all entry fields including cross-references to IDP-related resources such as DisProt, MobiDB, BMRB and SASBDB. We expect that the renewed PED will be useful for researchers interested in the atomic-level understanding of IDP function, and promote the rational, structure-based design of IDP-targeting drugs. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited.},

note = {Cited by: 93; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mistry2021D412,

title = {Pfam: The protein families database in 2021},

author = {Jaina Mistry and Sara Chuguransky and Lowri Williams and Matloob Qureshi and Gustavo A. Salazar and Erik L. L. Sonnhammer and Silvio C. E. Tosatto and Lisanna Paladin and Shriya Raj and Lorna J. Richardson and Robert D. Finn and Alex Bateman},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099428285\&doi=10.109%2fna%2fgkaa913\&partnerID=40\&md5=6da16529eea077b4a9fc021675f4a745},

doi = {10.1093/nar/gkaa913},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {D1},

pages = {D412 \textendash D419},

publisher = {Oxford University Press},

abstract = {The Pfam database is a widely used resource for classifying protein sequences into families and domains. Since Pfam was last described in this journal, over 350 new families have been added in Pfam 33.1 and numerous improvements have been made to existing entries. To facilitate research on COVID-19, we have revised the Pfam entries that cover the SARS-CoV-2 proteome, and built new entries for regions that were not covered by Pfam. We have reintroduced Pfam-B which provides an automatically generated supplement to Pfam and contains 136 730 novel clusters of sequences that are not yet matched by a Pfam family. The new Pfam-B is based on a clustering by the MMseqs2 software. We have compared all of the regions in the RepeatsDB to those in Pfam and have started to use the results to build and refine Pfam repeat families. Pfam is freely available for browsing and download at http://pfam.xfam.org/. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 3071; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piovesan2021D361,

title = {MobiDB: Intrinsically disordered proteins in 2021},

author = {Damiano Piovesan and Marco Necci and Nahuel Escobedo and Alexander Miguel Monzon and Andr\'{a}s Hatos and Ivan Mi\v{c}eti\'{c} and Federica Quaglia and Lisanna Paladin and Pathmanaban Ramasamy and Zsuzsanna Doszt\'{a}nyi and Wim F. Vranken and Norman E. Davey and Gustavo Parisi and Monika Fuxreiter and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099427471\&doi=10.109%2fna%2fgkaa1058\&partnerID=40\&md5=a349acef72c8e82f889845d00b32a673},

doi = {10.1093/nar/gkaa1058},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {D1},

pages = {D361 \textendash D367},

publisher = {Oxford University Press},

abstract = {The MobiDB database (URL: https://mobidb.org/) provides predictions and annotations for intrinsically disordered proteins. Here, we report recent developments implemented in MobiDB version 4, regarding the database format, with novel types of annotations and an improved update process. The new website includes a re-designed user interface, a more effective search engine and advanced API for programmatic access. The new database schema gives more flexibility for the users, as well as simplifying the maintenance and updates. In addition, the new entry page provides more visualisation tools including customizable feature viewer and graphs of the residue contact maps. MobiDB v4 annotates the binding modes of disordered proteins, whether they undergo disorder-to-order transitions or remain disordered in the bound state. In addition, disordered regions undergoing liquid-liquid phase separation or post-translational modifications are defined. The integrated information is presented in a simplified interface, which enables faster searches and allows large customized datasets to be downloaded in TSV, Fasta or JSON formats. An alternative advanced interface allows users to drill deeper into features of interest. A new statistics page provides information at database and proteome levels. The new MobiDB version presents state-of-the-art knowledge on disordered proteins and improves data accessibility for both computational and experimental users. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.},

note = {Cited by: 154; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Rocca2021,

title = {Identification of rare lrp5 variants in a cohort of males with impaired bone mass},

author = {Maria Santa Rocca and Giovanni Minervini and Andrea Di Nisio and Maurizio Merico and Maria Bueno Marinas and Luca De Toni and Kalliopi Pilichou and Andrea Garolla and Carlo Foresta and Alberto Ferlin},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85116416860\&doi=10.339%2fijms221910834\&partnerID=40\&md5=0720864aebf74dfe5c3085da131bd69a},

doi = {10.3390/ijms221910834},

issn = {16616596},

year  = {2021},

date = {2021-01-01},

journal = {International Journal of Molecular Sciences},

volume = {22},

number = {19},

publisher = {MDPI},

abstract = {Osteoporosis is the most common bone disease characterized by reduced bone mass and increased bone fragility. Genetic contribution is one of the main causes of primary osteoporosis; therefore, both genders are affected by this skeletal disorder. Nonetheless, osteoporosis in men has received little attention, thus being underestimated and undertreated. The aim of this study was to identify novel genetic variants in a cohort of 128 males with idiopathic low bone mass using a next-generation sequencing (NGS) panel including genes whose mutations could result in reduced bone mineral density (BMD). Genetic analysis detected in eleven patients ten rare heterozygous variants within the LRP5 gene, which were categorized as VUS (variant of uncertain significance), likely pathogenic and benign variants according to American College of Medical Genetics and Genomics (ACMG) guidelines. Protein structural and Bayesian analysis performed on identified LRP5 variants pointed out p.R1036Q and p.R1135C as pathogenic, therefore suggesting the likely association of these two variants with the low bone mass phenotype. In conclusion, this study expands our understanding on the importance of a functional LRP5 protein in bone formation and highlights the necessity to sequence this gene in subjects with idiopathic low BMD. © 2021 by the authorsLicensee MDPI, Basel, Switzerland.},

note = {Cited by: 4; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Balatti202113366,

title = {Intrinsically Disordered Region Modulates Ligand Binding in Glutaredoxin 1 from Trypanosoma Brucei},

author = {Galo. E. Balatti and G. Patricio Barletta and Gustavo Parisi and Silvio. C. E. Tosatto and Massimo Bellanda and Sebastian Fernandez-Alberti},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85121123474\&doi=10.102%2facs.jpcb.1c07035\&partnerID=40\&md5=0c9b068123b32551ce5a76b53c8893f1},

doi = {10.1021/acs.jpcb.1c07035},

issn = {15206106},

year  = {2021},

date = {2021-01-01},

journal = {Journal of Physical Chemistry B},

volume = {125},

number = {49},

pages = {13366 \textendash 13375},

publisher = {American Chemical Society},

abstract = {Glutaredoxins are small proteins that share a common well-conserved thioredoxin-fold and participate in a wide variety of biological processes. Among them, class II Grx are redox-inactive proteins involved in iron\textendashsulfur (Fe-S) metabolism. In the present work, we report different structural and dynamics aspects of 1CGrx1 from the pathogenic parasite Trypanosoma brucei that differentiate it from other orthologues by the presence of a parasite-specific unstructured N-terminal extension whose role has not been fully elucidated yet. Previous nuclear magnetic resonance (NMR) studies revealed significant differences with respect to the mutant lacking the disordered tail. Herein, we have performed atomistic molecular dynamics simulations that, complementary to NMR studies, confirm the intrinsically disordered nature of the N-terminal extension. Moreover, we confirm the main role of these residues in modulating the conformational dynamics of the glutathione-binding pocket. We observe that the N-terminal extension modifies the ligand cavity stiffening it by specific interactions that ultimately modulate its intrinsic flexibility, which may modify its role in the storage and/or transfer of preformed iron\textendashsulfur clusters. These unique structural and dynamics aspects of Trypanosoma brucei 1CGrx1 differentiate it from other orthologues and could have functional relevance. In this way, our results encourage the study of other similar protein folding families with intrinsically disordered regions whose functional roles are still unrevealed and the screening of potential 1CGrx1 inhibitors as antitrypanosomal drug candidates. © 2021 American Chemical Society},

note = {Cited by: 3},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Csizmadia2021D355,

title = {The MemMoRF database for recognizing disordered protein regions interacting with cellular membranes},

author = {Georgina Csizmadia and G\'{a}bor Erd\H{o}s and Hedvig Tordai and Rita Pad\'{a}nyi and Silvio Tosatto and Zsuzsanna Doszt\'{a}nyi and Tam\'{a}s Heged\H{u}s},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099428815\&doi=10.109%2fna%2fgkaa954\&partnerID=40\&md5=52bde6b75921ce80ccf3a2c21243237c},

doi = {10.1093/nar/gkaa954},

issn = {03051048},

year  = {2021},

date = {2021-01-01},

journal = {Nucleic Acids Research},

volume = {49},

number = {D1},

pages = {D355 \textendash D360},

publisher = {Oxford University Press},

abstract = {Protein and lipid membrane interactions play fundamental roles in a large number of cellular processes (e.g. signalling, vesicle trafficking, or viral invasion). A growing number of examples indicate that such interactions can also rely on intrinsically disordered protein regions (IDRs), which can form specific reversible interactions not only with proteins but also with lipids. We named IDRs involved in such membrane lipid-induced disorder-to-order transition as MemMoRFs, in an analogy to IDRs exhibiting disorder-to-order transition upon interaction with protein partners termed Molecular Recognition Features (MoRFs). Currently, both the experimental detection and computational characterization of MemMoRFs are challenging, and information about these regions are scattered in the literature. To facilitate the related investigations we generated a comprehensive database of experimentally validated MemMoRFs based on manual curation of literature and structural data. To characterize the dynamics of MemMoRFs, secondary structure propensity and flexibility calculated from nuclear magnetic resonance chemical shifts were incorporated into the database. These data were supplemented by inclusion of sentences from papers, functional data and disease-related information. The MemMoRF database can be accessed via a user-friendly interface at https://memmorf.hegelab.org, potentially providing a central resource for the characterization of disordered regions in transmembrane and membrane-associated proteins. © The Author(s) 2020. Published by Oxford University Press on behalf of Nucleic Acids Research. This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com},

note = {Cited by: 8; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Mier2020458,

title = {Disentangling the complexity of low complexity proteins},

author = {Pablo Mier and Lisanna Paladin and Stella Tamana and Sophia Petrosian and Borb\'{a}la Hajdu-Solt\'{e}sz and Annika Urbanek and Aleksandra Gruca and Dariusz Plewczynski and Marcin Grynberg and Pau Bernad\'{o} and Zolt\'{a}n G\'{a}sp\'{a}ri and Christos A. Ouzounis and Vasilis J. Promponas and Andrey V. Kajava and John M Hancock and Silvio C. E. Tosatto and Zsuzsanna Dosztanyi and Miguel A. Andrade-Navarro},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083811469\&doi=10.109%2fbi%2fbbz007\&partnerID=40\&md5=47cf39e1999d8381365bf6821122f9f4},

doi = {10.1093/bib/bbz007},

issn = {14675463},

year  = {2020},

date = {2020-01-01},

journal = {Briefings in Bioinformatics},

volume = {21},

number = {2},

pages = {458 \textendash 472},

publisher = {Oxford University Press},

abstract = {There are multiple definitions for low complexity regions (LCRs) in protein sequences, with all of them broadly considering LCRs as regions with fewer amino acid types compared to an average composition. Following this view, LCRs can also be defined as regions showing composition bias. In this critical review, we focus on the definition of sequence complexity of LCRs and their connection with structure. We present statistics and methodological approaches that measure low complexity (LC) and related sequence properties. Composition bias is often associated with LC and disorder, but repeats, while compositionally biased, might also induce ordered structures. We illustrate this dichotomy, and more generally the overlaps between different properties related to LCRs, using examples. We argue that statistical measures alone cannot capture all structural aspects of LCRs and recommend the combined usage of a variety of predictive tools and measurements. While the methodologies available to study LCRs are already very advanced, we foresee that a more comprehensive annotation of sequences in the databases will enable the improvement of predictions and a better understanding of the evolution and the connection between structure and function of LCRs. This will require the use of standards for the generation and exchange of data describing all aspects of LCRs. Short abstract: There are multiple definitions for low complexity regions (LCRs) in protein sequences. In this critical review, we focus on the definition of sequence complexity of LCRs and their connection with structure. We present statistics and methodological approaches that measure low complexity (LC) and related sequence properties. Composition bias is often associated with LC and disorder, but repeats, while compositionally biased, might also induce ordered structures. We illustrate this dichotomy, plus overlaps between different properties related to LCRs, using examples. © 2019 The Author(s) 2019. Published by Oxford University Press.},

note = {Cited by: 64; All Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Reggiani2020,

title = {In silico prediction of blood cholesterol levels from genotype data},

author = {Francesco Reggiani and Marco Carraro and Anna Belligoli and Marta Sanna and Chiara Pr\`{a} and Francesca Favaretto and Carlo Ferrari and Roberto Vettor and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85079208028\&doi=10.137%2fjournal.pone.0227191\&partnerID=40\&md5=8d43519160bcd1590b8f7d0138a8b791},

doi = {10.1371/journal.pone.0227191},

issn = {19326203},

year  = {2020},

date = {2020-01-01},

journal = {PLoS ONE},

volume = {15},

number = {2},

publisher = {Public Library of Science},

abstract = {In this work we present a framework for blood cholesterol levels prediction from genotype data. The predictor is based on an algorithm for cholesterol metabolism simulation available in literature, implemented and optimized by our group in the R language. The main weakness of the former simulation algorithm was the need of experimental data to simulate mutations in genes altering the cholesterol metabolism. This caveat strongly limited the application of the model in the clinical practice. In this work we present how this limitation could be bypassed thanks to an optimization of model parameters based on patient cholesterol levels retrieved from literature. Prediction performance has been assessed taking into consideration several scoring indices currently used for performance evaluation of machine learning methods. Our assessment shows how the optimization phase improved model performance, compared to the original version available in literature. © 2020 Reggiani et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},

note = {Cited by: 3; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Saldan\~{o}20203068,

title = {Exploring Conformational Space with Thermal Fluctuations Obtained by Normal-Mode Analysis},

author = {Tadeo E. Saldan\~{o} and Victor M. Freixas and Silvio C. E. Tosatto and Gustavo Parisi and Sebastian Fernandez-Alberti},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086793285\&doi=10.102%2facs.jcim.9b01136\&partnerID=40\&md5=b3ced251679d8be814e39e8707f320e0},

doi = {10.1021/acs.jcim.9b01136},

issn = {15499596},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Chemical Information and Modeling},

volume = {60},

number = {6},

pages = {3068 \textendash 3080},

publisher = {American Chemical Society},

abstract = {Proteins in their native states can be represented as ensembles of conformers in dynamical equilibrium. Thermal fluctuations are responsible for transitions between these conformers. Normal-modes analysis (NMA) using elastic network models (ENMs) provides an efficient procedure to explore global dynamics of proteins commonly associated with conformational transitions. In the present work, we present an iterative approach to explore protein conformational spaces by introducing structural distortions according to their equilibrium dynamics at room temperature. The approach can be used either to perform unbiased explorations of conformational space or to explore guided pathways connecting two different conformations, e.g., apo and holo forms. In order to test its performance, four proteins with different magnitudes of structural distortions upon ligand binding have been tested. In all cases, the conformational selection model has been confirmed and the conformational space between apo and holo forms has been encompassed. Different strategies have been tested that impact on the efficiency either to achieve a desired conformational change or to achieve a balanced exploration of the protein conformational multiplicity. © 2020 American Chemical Society.},

note = {Cited by: 3},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Iserte2020,

title = {Chasing coevolutionary signals in intrinsically disordered proteins complexes},

author = {Javier A. Iserte and Tamas Lazar and Silvio C. E. Tosatto and Peter Tompa and Cristina Marino-Buslje},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85093107322\&doi=10.103%2fs41598-020-74791-6\&partnerID=40\&md5=1cdea5a59dc3f2747198d9192f0a7cc6},

doi = {10.1038/s41598-020-74791-6},

issn = {20452322},

year  = {2020},

date = {2020-01-01},

journal = {Scientific Reports},

volume = {10},

number = {1},

publisher = {Nature Research},

abstract = {Intrinsically disordered proteins/regions (IDPs/IDRs) are crucial components of the cell, they are highly abundant and participate ubiquitously in a wide range of biological functions, such as regulatory processes and cell signaling. Many of their important functions rely on protein interactions, by which they trigger or modulate different pathways. Sequence covariation, a powerful tool for protein contact prediction, has been applied successfully to predict protein structure and to identify protein\textendashprotein interactions mostly of globular proteins. IDPs/IDRs also mediate a plethora of protein\textendashprotein interactions, highlighting the importance of addressing sequence covariation-based inter-protein contact prediction of this class of proteins. Despite their importance, a systematic approach to analyze the covariation phenomena of intrinsically disordered proteins and their complexes is still missing. Here we carry out a comprehensive critical assessment of coevolution-based contact prediction in IDP/IDR complexes and detail the challenges and possible limitations that emerge from their analysis. We found that the coevolutionary signal is faint in most of the complexes of disordered proteins but positively correlates with the interface size and binding affinity between partners. In addition, we discuss the state-of-art methodology by biological interpretation of the results, formulate evaluation guidelines and suggest future directions of development to the field. © 2020, The Author(s).},

note = {Cited by: 6; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Galber20201199,

title = {The role of mitochondrial ATP synthase in cancer},

author = {Chiara Galber and Manuel Jesus Acosta and Giovanni Minervini and Valentina Giorgio},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092318936\&doi=10.151%2fhsz-2020-0157\&partnerID=40\&md5=d347b3c6f7911407dfb5a0375b3899a9},

doi = {10.1515/hsz-2020-0157},

issn = {14316730},

year  = {2020},

date = {2020-01-01},

journal = {Biological Chemistry},

volume = {401},

number = {11},

pages = {1199 \textendash 1214},

publisher = {De Gruyter Open Ltd},

abstract = {The mitochondrial ATP synthase is a multi-subunit enzyme complex located in the inner mitochondrial membrane which is essential for oxidative phosphorylation under physiological conditions. In this review, we analyse the enzyme functions involved in cancer progression by dissecting specific conditions in which ATP synthase contributes to cancer development or metastasis. Moreover, we propose the role of ATP synthase in the formation of the permeability transition pore (PTP) as an additional mechanism which controls tumour cell death. We further describe transcriptional and translational modifications of the enzyme subunits and of the inhibitor protein IF1 that may promote adaptations leading to cancer metabolism. Finally, we outline ATP synthase gene mutations and epigenetic modifications associated with cancer development or drug resistance, with the aim of highlighting this enzyme complex as a potential novel target for future anti-cancer therapy. © 2020 De Gruyter. All rights reserved.},

note = {Cited by: 34; All Open Access, Hybrid Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Hatos2020D269,

title = {DisProt: Intrinsic protein disorder annotation in 2020},

author = {Andr\'{a}s Hatos and Borb\'{a}la Hajdu-Solt\'{e}sz and Alexander M. Monzon and Nicolas Palopoli and Luc\'{i}a \'{A}lvarez and Burcu Aykac-Fas and Claudio Bassot and Guillermo I. Ben\'{i}tez and Martina Bevilacqua and Anastasia Chasapi and Lucia Chemes and Norman E. Davey and Radoslav Davidovi\'{c} and A Keith Dunker and Arne Elofsson and Julien Gobeill and Nicol\'{a}s S Gonz\'{a}lez Foutel and Govindarajan Sudha and Mainak Guharoy and Tamas Horvath and Valentin Iglesias and Andrey V. Kajava and Orsolya P. Kovacs and John Lamb and Matteo Lambrughi and Tamas Lazar and Jeremy Y. Leclercq and Emanuela Leonardi and Sandra MacEdo-Ribeiro and Mauricio MacOssay-Castillo and Emiliano Maiani and Jos\'{e} A. Manso and Cristina Marino-Buslje and Elizabeth Mart\'{i}nez-P\'{e}rez and B\'{a}lint M\'{e}sz\'{a}ros and Ivan Mi\v{c}eti\'{c} and Giovanni Minervini and Nikoletta Murvai and Marco Necci and Christos A. Ouzounis and M\'{a}ty\'{a}s Pajkos and Lisanna Paladin and Rita Pancsa and Elena Papaleo and Gustavo Parisi and Emilie Pasche and Pedro J. Barbosa Pereira and Vasilis J. Promponas and Jordi Pujols and Federica Quaglia and Patrick Ruch and Marco Salvatore and Eva Schad and Beata Szabo and Tam\'{a}s Szaniszl\'{o} and Stella Tamana and Agnes Tantos and Nevena Veljkovic and Salvador Ventura and Wim Vranken and Zsuzsanna Doszt\'{a}nyi and Peter Tompa and Silvio C. E. Tosatto and Damiano Piovesan},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85077666918\&doi=10.109%2fna%2fgkz975\&partnerID=40\&md5=9cc031113f613fdf6e77a58babe61916},

doi = {10.1093/nar/gkz975},

issn = {03051048},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Research},

volume = {48},

number = {D1},

pages = {D269 \textendash D276},

publisher = {Oxford University Press},

abstract = {The Database of Protein Disorder (DisProt, URL: https://disprot.org) provides manually curated annotations of intrinsically disordered proteins from the literature. Here we report recent developments with DisProt (version 8), including the doubling of protein entries, a new disorder ontology, improvements of the annotation format and a completely new website. The website includes a redesigned graphical interface, a better search engine, a clearer API for programmatic access and a new annotation interface that integrates text mining technologies. The new entry format provides a greater flexibility, simplifies maintenance and allows the capture of more information from the literature. The new disorder ontology has been formalized and made interoperable by adopting the OWL format, as well as its structure and term definitions have been improved. The new annotation interface has made the curation process faster and more effective. We recently showed that new DisProt annotations can be effectively used to train and validate disorder predictors. We believe the growth of DisProt will accelerate, contributing to the improvement of function and disorder predictors and therefore to illuminate the 'dark' proteome. © 2019 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 187; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Necci20205533,

title = {MobiDB-lite 3.0: Fast consensus annotation of intrinsic disorder flavors in proteins},

author = {Marco Necci and Damiano Piovesan and Damiano Clementel and Zsuzsanna Doszt\'{a}nyi and Silvio C. E Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85100492379\&doi=10.109%2fbioinformatic%2fbtaa1045\&partnerID=40\&md5=3b93e83456cc54b2d6a4a791b5ddbd25},

doi = {10.1093/bioinformatics/btaa1045},

issn = {13674803},

year  = {2020},

date = {2020-01-01},

journal = {Bioinformatics},

volume = {36},

number = {22-23},

pages = {5533 \textendash 5534},

publisher = {Oxford University Press},

abstract = {Motivation: The earlier version of MobiDB-lite is currently used in large-scale proteome annotation platforms to detect intrinsic disorder. However, new theoretical models allow for the classification of intrinsically disordered regions into subtypes from sequence features associated with specific polymeric properties or compositional bias. Results: MobiDB-lite 3.0 maintains its previous speed and performance but also provides a finer classification of disorder by identifying regions with characteristics of polyolyampholytes, positive or negative polyelectrolytes, low-complexity regions or enriched in cysteine, proline or glycine or polar residues. Subregions are abundantly detected in IDRs of the human proteome. The new version of MobiDB-lite represents a new step for the proteome level analysis of protein disorder. © 2020 The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.},

note = {Cited by: 50; All Open Access, Bronze Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{M\'{e}sz\'{a}ros2020D360,

title = {PhaSePro: The database of proteins driving liquid-liquid phase separation},

author = {B\'{a}lint M\'{e}sz\'{a}ros and G\'{a}bor Erdos and Be\'{a}ta Szab\'{o} and \'{E}va Sch\'{a}d and \'{A}gnes Tantos and Rawan Abukhairan and Tam\'{a}s Horv\'{a}th and Nikoletta Murvai and Orsolya P. Kov\'{a}cs and M\'{a}rton Kov\'{a}cs and Silvio C. E. Tosatto and P\'{e}ter Tompa and Zsuzsanna Doszt\'{a}nyi and Rita Pancsa},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85070436802\&doi=10.109%2fna%2fgkz848\&partnerID=40\&md5=d251acc60caab8abf7b403fd1ad953b5},

doi = {10.1093/nar/gkz848},

issn = {03051048},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Research},

volume = {48},

number = {D1},

pages = {D360 \textendash D367},

publisher = {Oxford University Press},

abstract = {Membraneless organelles (MOs) are dynamic liquid condensates that host a variety of specific cellular processes, such as ribosome biogenesis or RNA degradation. MOs form through liquid-liquid phase separation (LLPS), a process that relies on multivalent weak interactions of the constituent proteins and other macromolecules. Since the first discoveries of certain proteins being able to drive LLPS, it emerged as a general mechanism for the effective organization of cellular space that is exploited in all kingdoms of life. While numerous experimental studies report novel cases, the computational identification of LLPS drivers is lagging behind, and many open questions remain about the sequence determinants, composition, regulation and biological relevance of the resulting condensates. Our limited ability to overcome these issues is largely due to the lack of a dedicated LLPS database. Therefore, here we introduce PhaSePro (https://phasepro.elte.hu), an openly accessible, comprehensive, manually curated database of experimentally validated LLPS driver proteins/protein regions. It not only provides a wealth of information on such systems, but improves the standardization of data by introducing novel LLPS-specific controlled vocabularies. PhaSePro can be accessed through an appealing, user-friendly interface and thus has definite potential to become the central resource in this dynamically developing field. © 2019 The Author(s). Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 130; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Paladin2020,

title = {A novel approach to investigate the evolution of structured tandem repeat protein families by exon duplication},

author = {Lisanna Paladin and Marco Necci and Damiano Piovesan and Pablo Mier and Miguel A. Andrade-Navarro and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85090971828\&doi=10.101%2fj.jsb.2020.107608\&partnerID=40\&md5=1455611268e320d8f914b65e4888bf62},

doi = {10.1016/j.jsb.2020.107608},

issn = {10478477},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Structural Biology},

volume = {212},

number = {2},

publisher = {Academic Press Inc.},

abstract = {Tandem Repeat Proteins (TRPs) are ubiquitous in cells and are enriched in eukaryotes. They contributed to the evolution of organism complexity, specializing for functions that require quick adaptability such as immunity-related functions. To investigate the hypothesis of repeat protein evolution through exon duplication and rearrangement, we designed a tool to analyze the relationships between exon/intron patterns and structural symmetries. The tool allows comparison of the structure fragments as defined by exon/intron boundaries from Ensembl against the structural element repetitions from RepeatsDB. The all-against-all pairwise structural alignment between fragments and comparison of the two definitions (structural units and exons) are visualized in a single matrix, the “repeat/exon plot”. An analysis of different repeat protein families, including the solenoids Leucine-Rich, Ankyrin, Pumilio, HEAT repeats and the β propellers Kelch-like, WD40 and RCC1, shows different behaviors, illustrated here through examples. For each example, the analysis of the exon mapping in homologous proteins supports the conservation of their exon patterns. We propose that when a clear-cut relationship between exon and structural boundaries can be identified, it is possible to infer a specific “evolutionary pattern” which may improve TRPs detection and classification. © 2020 Elsevier Inc.},

note = {Cited by: 9},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Carletti2020,

title = {Revenant: A database of resurrected proteins},

author = {Matias Sebastian Carletti and Alexander Miguel Monzon and Emilio Garcia-Rios and Guillermo Benitez and Layla Hirsh and Maria Silvina Fornasari and Gustavo Parisi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084626047\&doi=10.109%2fdatabas%2fbaaa031\&partnerID=40\&md5=7c8360c976b26c39657c3ed04b08802c},

doi = {10.1093/database/baaa031},

issn = {17580463},

year  = {2020},

date = {2020-01-01},

journal = {Database},

volume = {2020},

publisher = {Oxford University Press},

abstract = {Revenant is a database of resurrected proteins coming from extinct organisms. Currently, it contains a manually curated collection of 84 resurrected proteins derived from bibliographic data. Each protein is extensively annotated, including structural, biochemical and biophysical information. Revenant contains a browse capability designed as a timeline from where the different proteins can be accessed. The oldest Revenant entries are between 4200 and 3500 million years ago, while the younger entries are between 8.8 and 6.3 million years ago. These proteins have been resurrected using computational tools called ancestral sequence reconstruction techniques combined with wet-laboratory synthesis and expression. Resurrected proteins are commonly used, with a noticeable increase during the past years, to explore and test different evolutionary hypotheses such as protein stability, to explore the origin of new functions, to get biochemical insights into past metabolisms and to explore specificity and promiscuous behaviour of ancient proteins. © 2020 The Author(s) 2020. Published by Oxford University Press.},

note = {Cited by: 6; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Kaur2020650,

title = {Expanding the genetic landscape of Rett syndrome to include lysine acetyltransferase 6A (KAT6A)},

author = {Simranpreet Kaur and Nicole J. Van Bergen and Bruria Ben-Zeev and Emanuela Leonardi and Tiong Y. Tan and David Coman and Benjamin Kamien and Susan M. White and Miya St John and Dean Phelan and Kristin Rigbye and Sze Chern Lim and Michelle C. Torres and Melanie Marty and Elena Savva and Teresa Zhao and Sean Massey and Alessandra Murgia and Wendy A. Gold and John Christodoulou},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85099166712\&doi=10.101%2fj.jgg.2020.09.003\&partnerID=40\&md5=93619e11a45e2af12e87a5519c25e6fb},

doi = {10.1016/j.jgg.2020.09.003},

issn = {16738527},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Genetics and Genomics},

volume = {47},

number = {10},

pages = {650 \textendash 654},

publisher = {Institute of Genetics and Developmental Biology},

note = {Cited by: 2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Cesca2020855,

title = {Frequency of Usher gene mutations in non-syndromic hearing loss: higher variability of the Usher phenotype},

author = {Federica Cesca and Elisa Bettella and Roberta Polli and Emanuela Leonardi and Maria Cristina Aspromonte and Barbara Sicilian and Franco Stanzial and Francesco Benedicenti and Alberto Sensi and Andrea Ciorba and Stefania Bigoni and Elona Cama and Pietro Scimemi and Rosamaria Santarelli and Alessandra Murgia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85085478685\&doi=10.103%2fs10038-020-0783-1\&partnerID=40\&md5=14dfffed6f51434ee852e8c1ab314cc6},

doi = {10.1038/s10038-020-0783-1},

issn = {14345161},

year  = {2020},

date = {2020-01-01},

journal = {Journal of Human Genetics},

volume = {65},

number = {10},

pages = {855 \textendash 864},

publisher = {Springer Nature},

abstract = {Non-syndromic hearing loss (NSHL) is characterized by a vast genetic heterogeneity; some syndromic forms as Usher syndrome (USH) have onset as isolated deafness and then evolve later in life. We developed an NGS targeted gene-panel containing 59 genes and a customized bioinformatic pipeline for the analysis of DNA samples from clinically highly selected subjects with sensorineural hearing loss, previously resulted negative for GJB2 mutations/GJB6 deletions. Among the 217 tested subjects, 24 (11.%) were found to carry mutations in genes involved both in NSHL and USH. For 6 out of 24 patients a diagnosis of USH was performed. Eleven subjects out of 24 had hearing loss without vestibular or ocular dysfunction and, due to their young age, it was not possible to establish whether their phenotype could be NSHL or USH. Seven subjects were diagnosed with NSHL, due to their age and phenotype. A total of 41 likely pathogenic/pathogenic mutations were identified, among which 17 novel ones. We report a high frequency of mutations in genes involved both in NSHL and in USH in a cohort of individuals tested for seemingly isolated deafness. Our data also highlight a wider than expected phenotypic variability in the USH phenotype. © 2020, The Author(s), under exclusive licence to The Japan Society of Human Genetics.},

note = {Cited by: 7},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Minervini2020,

title = {The pVHL neglected functions, a tale of hypoxia-dependent and -independent regulations in cancer},

author = {Giovanni Minervini and Maria Pennuto and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087390580\&doi=10.109%2frsob.200109\&partnerID=40\&md5=112d4094e068668876c98ead2abcc7df},

doi = {10.1098/rsob.200109},

issn = {20462441},

year  = {2020},

date = {2020-01-01},

journal = {Open Biology},

volume = {10},

number = {7},

publisher = {Royal Society Publishing},

abstract = {The von Hippel-Lindau protein (pVHL) is a tumour suppressor mainly known for its role as master regulator of hypoxia-inducible factor (HIF) activity. Functional inactivation of pVHL is causative of the von Hippel-Lindau disease, an inherited predisposition to develop different cancers. Due to its impact on human health, pVHL has been widely studied in the last few decades. However, investigations mostly focus on its role in degrading HIFs, whereas alternative pVHL protein-protein interactions and functions are insistently surfacing in the literature. In this review, we analyse these almost neglected functions by dissecting specific conditions in which pVHL is proposed to have differential roles in promoting cancer. We reviewed its role in regulating phosphorylation as a number of works suggest pVHL to act as an inhibitor by either degrading or promoting downregulation of specific kinases. Further, we summarize hypoxia-dependent and -independent pVHL interactions with multiple protein partners and discuss their implications in tumorigenesis. © 2020 The Authors.},

note = {Cited by: 17; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{DeBortoli2020E002824,

title = {Novel Missense Variant in MYL2 Gene Associated with Hypertrophic Cardiomyopathy Showing High Incidence of Restrictive Physiology},

author = {Marzia De Bortoli and Riccardo Vio and Cristina Basso and Martina Calore and Giovanni Minervini and Annalisa Angelini and Paola Melacini and Libero Vitiello and Giovanni Vazza and Gaetano Thiene and Silvio Tosatto and Domenico Corrado and Sabino Iliceto and Alessandra Rampazzo and Chiara Calore},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85083902829\&doi=10.116%2fCIRCGEN.119.002824\&partnerID=40\&md5=cf0abba828f4d17e79132045e6b83a40},

doi = {10.1161/CIRCGEN.119.002824},

issn = {25748300},

year  = {2020},

date = {2020-01-01},

journal = {Circulation: Genomic and Precision Medicine},

volume = {13},

number = {4},

pages = {E002824},

publisher = {Lippincott Williams and Wilkins},

note = {Cited by: 12; All Open Access, Bronze Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Paladin20203244,

title = {The Feature-Viewer: A visualization tool for positional annotations on a sequence},

author = {Lisanna Paladin and Mathieu Schaeffer and Pascale Gaudet and Monique Zahn-Zabal and Pierre-Andr\'{e} Michel and Damiano Piovesan and Silvio C. E. Tosatto and Amos Bairoch},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85084693969\&doi=10.109%2fbioinformatic%2fbtaa055\&partnerID=40\&md5=dc7a76f3d8645fd5e28bdbc4f52abea9},

doi = {10.1093/bioinformatics/btaa055},

issn = {13674803},

year  = {2020},

date = {2020-01-01},

journal = {Bioinformatics},

volume = {36},

number = {10},

pages = {3244 \textendash 3245},

publisher = {Oxford University Press},

abstract = {The Feature-Viewer is a lightweight library for the visualization of biological data mapped to a protein or nucleotide sequence. It is designed for ease of use while allowing for a full customization. The library is already used by several biological data resources and allows intuitive visual mapping of a full spectra of sequence features for different usages. © 2020 The Author(s). Published by Oxford University Press. All rights reserved.},

note = {Cited by: 17; All Open Access, Bronze Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vera2020,

title = {Clinical and molecular description of 19 patients with GATAD2B-Associated Neurodevelopmental Disorder (GAND)},

author = {Gabriella Vera and Arthur Sorlin and Geoffroy Delplancq and Fran\c{c}ois Lecoquierre and Marie Brasseur-Daudruy and Florence Petit and Thomas Smol and Alban Ziegler and Dominique Bonneau and Estelle Colin and Sandra Mercier and Benjamin Cogn\'{e} and St\'{e}phane B\'{e}zieau and Patrick Edery and Gaetan Lesca and Nicolas Chatron and Isabelle Sabatier and B\'{e}n\'{e}dicte Duban-Bedu and Cindy Colson and Am\'{e}lie Piton and Benjamin Durand and Yline Capri and Laurence Perrin and Antje Wiesener and Christiane Zweier and Reza Maroofian and Christopher J. Carroll and Hamid Galehdari and Neda Mazaheri and Bert Callewaert and Fabienne Giulianno and Khaoula Zaafrane-Khachnaoui and Rebecca Buchert-Lo and Tobias Haack and Janine Magg and Angelika Rie\ss and Maria Blandfort and Stephan Waldm\"{u}ller and Veronka Horber and Emanuela Leonardi and Roberta Polli and Licia Turolla and Alessandra Murgia and Thierry Frebourg and Anne Sophie Lebre and Ga\"{e}l Nicolas and Pascale Saugier-Veber and Anne-Marie Guerrot},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85089246670\&doi=10.101%2fj.ejmg.2020.104004\&partnerID=40\&md5=296955c2b38d812aa9104abf85762ddc},

doi = {10.1016/j.ejmg.2020.104004},

issn = {17697212},

year  = {2020},

date = {2020-01-01},

journal = {European Journal of Medical Genetics},

volume = {63},

number = {10},

publisher = {Elsevier Masson SAS},

abstract = {De novo pathogenic variants in the GATAD2B gene have been associated with a syndromic neurodevelopmental disorder (GAND) characterized by severe intellectual disability (ID), impaired speech, childhood hypotonia, and dysmorphic features. Since its first description in 2013, nine patients have been reported in case reports and a series of 50 patients was recently published, which is consistent with the relative frequency of GATAD2B pathogenic variants in public databases. We report the detailed phenotype of 19 patients from various ethnic backgrounds with confirmed pathogenic GATAD2B variants including intragenic deletions. All individuals presented developmental delay with a median age of 2.5 years for independent walking and of 3 years for first spoken words. GATAD2B variant carriers showed very little subsequent speech progress, two patients over 30 years of age remaining non-verbal. ID was mostly moderate to severe, with one profound and one mild case, which shows a wider spectrum of disease severity than previously reported. We confirm macrocephaly as a major feature in GAND (5%). Most common dysmorphic features included broad forehead, deeply set eyes, hypertelorism, wide nasal base, and pointed chin. Conversely, prenatal abnormalities, non-cerebral malformations, epilepsy, and autistic behavior were uncommon. Other features included feeding difficulties, behavioral abnormalities, and unspecific abnormalities on brain MRI. Improving our knowledge of the clinical phenotype is essential for correct interpretation of the molecular results and accurate patient management. © 2020},

note = {Cited by: 9; All Open Access, Bronze Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Monzon2020127,

title = {Exploring protein intrinsic disorder with MobiDB},

author = {Alexander Miguel Monzon and Andr\'{a}s Hatos and Marco Necci and Damiano Piovesan and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85088508369\&doi=10.100%2f978-1-0716-0524-0_6\&partnerID=40\&md5=3bb92616dc17c8794c6c4d5d9fd79ccd},

doi = {10.1007/978-1-0716-0524-0_6},

issn = {10643745},

year  = {2020},

date = {2020-01-01},

journal = {Methods in Molecular Biology},

volume = {2141},

pages = {127 \textendash 143},

publisher = {Humana Press Inc.},

abstract = {Nowadays, it is well established that many proteins or regions under physiological conditions lack a fixed three-dimensional structure and are intrinsically disordered. MobiDB is the main repository of protein disorder and mobility annotations, combining different data sources to provide an exhaustive overview of intrinsic disorder. MobiDB includes curated annotations from other databases, indirect disorder evidence from structural data, and disorder predictions from protein sequences. It provides an easy-to-use web server to visualize and explore disorder information. This chapter describes the data available in MobiDB, emphasizing how to use and access the intrinsic disorder data. MobiDB is available at URL http://mobidb.bio.unipd.it. © Springer Science+Business Media, LLC, part of Springer Nature 2020.},

note = {Cited by: 2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Falconieri2020,

title = {The E3 ubiquitin-protein ligase MDM2 is a novel interactor of the von Hippel\textendashLindau tumor suppressor},

author = {Antonella Falconieri and Giovanni Minervini and Raissa Bortolotto and Damiano Piovesan and Raffaele Lopreiato and Geppo Sartori and Maria Pennuto and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85091666355\&doi=10.103%2fs41598-020-72683-3\&partnerID=40\&md5=906dd8dc10b4313d94a6a85e44733a6b},

doi = {10.1038/s41598-020-72683-3},

issn = {20452322},

year  = {2020},

date = {2020-01-01},

journal = {Scientific Reports},

volume = {10},

number = {1},

publisher = {Nature Research},

abstract = {Mutations of the von Hippel\textendashLindau (pVHL) tumor suppressor are causative of a familiar predisposition to develop different types of cancer. pVHL is mainly known for its role in regulating hypoxia-inducible factor 1 α (HIF-1α) degradation, thus modulating the hypoxia response. There are different pVHL isoforms, including pVHL30 and pVHL19. However, little is known about isoform-specific functions and protein\textendashprotein interactions. Integrating in silico predictions with in vitro and in vivo assays, we describe a novel interaction between pVHL and mouse double minute 2 homolog (MDM2). We found that pVHL30, and not pVHL19, forms a complex with MDM2, and that the N-terminal acidic tail of pVHL30 is required for its association with MDM2. Further, we demonstrate that an intrinsically disordered region upstream of the tetramerization domain of MDM2 is responsible for its isoform-specific association with pVHL30. This region is highly conserved in higher mammals, including primates, similarly to what has been already shown for the N-terminal tail of pVHL30. Finally, we show that overexpression of pVHL30 and MDM2 together reduces cell metabolic activity and necrosis, suggesting a synergistic effect of these E3 ubiquitin ligases. Collectively, our data show an isoform-specific interaction of pVHL with MDM2, suggesting an interplay between these two E3 ubiquitin ligases. © 2020, The Author(s).},

note = {Cited by: 4; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Jarnot2020W77,

title = {PlaToLoCo: The first web meta-server for visualization and annotation of low complexity regions in proteins},

author = {Patryk Jarnot and Joanna Ziemska-Legiecka and Laszlo Dobson and Matthew Merski and Pablo Mier and Miguel A. Andrade-Navarro and John M. Hancock and Zsuzsanna Doszt\'{a}nyi and Lisanna Paladin and Marco Necci and Damiano Piovesan and Silvio C. E. Tosatto and Vasilis J. Promponas and Marcin Grynberg and Aleksandra Gruca},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087320561\&doi=10.109%2fNA%2fGKAA339\&partnerID=40\&md5=aaa381c1b497b75781851e23725baf24},

doi = {10.1093/NAR/GKAA339},

issn = {03051048},

year  = {2020},

date = {2020-01-01},

journal = {Nucleic Acids Research},

volume = {48},

number = {W1},

pages = {W77 \textendash W84},

publisher = {Oxford University Press},

abstract = {Low complexity regions (LCRs) in protein sequences are characterized by a less diverse amino acid composition compared to typically observed sequence diversity. Recent studies have shown that LCRs may co-occur with intrinsically disordered regions, are highly conserved in many organisms, and often play important roles in protein functions and in diseases. In previous decades, several methods have been developed to identify regions with LCRs or amino acid bias, but most of them as stand-alone applications and currently there is no web-based tool which allows users to explore LCRs in protein sequences with additional functional annotations. We aim to fill this gap by providing PlaToLoCo-PLAtform of TOols for LOw COmplexity-a meta-server that integrates and collects the output of five different state-of-theart tools for discovering LCRs and provides functional annotations such as domain detection, transmembrane segment prediction, and calculation of amino acid frequencies. In addition, the union or intersection of the results of the search on a query sequence can be obtained. By developing the Pla-ToLoCo meta-server, we provide the community with a fast and easily accessible tool for the analysis of LCRs with additional information included to aid the interpretation of the results. The PlaToLoCo platform is available at: Http://platoloco.aei.polsl.pl/. © 2020 Oxford University Press. All rights reserved.},

note = {Cited by: 29; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Piovesan2020,

title = {Assessing predictors for new post translational modification sites: A case study on hydroxylation},

author = {Damiano Piovesan and Andras Hatos and Giovanni Minervini and Federica Quaglia and Alexander Miguel Monzon and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85087532447\&doi=10.137%2fjournal.pcbi.1007967\&partnerID=40\&md5=1a02438dbd602f64650f78015a89e7e4},

doi = {10.1371/journal.pcbi.1007967},

issn = {1553734X},

year  = {2020},

date = {2020-01-01},

journal = {PLoS Computational Biology},

volume = {16},

number = {6},

publisher = {Public Library of Science},

abstract = {Post-translational modification (PTM) sites have become popular for predictor development. However, with the exception of phosphorylation and a handful of other examples, PTMs suffer from a limited number of available training examples and sparsity in protein sequences. Here, proline hydroxylation is taken as an example to compare different methods and evaluate their performance on new experimentally determined sites. As a guide for effective experimental design, predictors require both high specificity and sensitivity. However, the self-reported performance may often not be indicative of prediction quality and detection of new sites is not guaranteed. We have benchmarked seven published hydroxylation site predictors on two newly constructed independent datasets. The self-reported performance is found to widely overestimate the real accuracy measured on independent datasets. No predictor performs better than random on new examples, indicating the refined models do not sufficiently generalize to detect new sites. The number of false positives is high and precision low, in particular for non-collagen proteins whose motifs are not conserved. As hydroxylation site predictors do not generalize for new data, caution is advised when using PTM predictors in the absence of independent evaluations, in particular for highly specific sites involved in signalling. Copyright: © 2020 Piovesan et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.},

note = {Cited by: 9; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leonardi2020,

title = {Identification of SETBP1 Mutations by Gene Panel Sequencing in Individuals With Intellectual Disability or With “Developmental and Epileptic Encephalopathy”},

author = {Emanuela Leonardi and Elisa Bettella and Maria Federica Pelizza and Maria Cristina Aspromonte and Roberta Polli and Clementina Boniver and Stefano Sartori and Donatella Milani and Alessandra Murgia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85098481915\&doi=10.338%2ffneur.2020.593446\&partnerID=40\&md5=04f1b67055162f3b253734d9efadf821},

doi = {10.3389/fneur.2020.593446},

issn = {16642295},

year  = {2020},

date = {2020-01-01},

journal = {Frontiers in Neurology},

volume = {11},

publisher = {Frontiers Media S.A.},

abstract = {SETBP1 mutations are associated with the Schinzel-Giedion syndrome (SGS), characterized by profound neurodevelopmental delay, typical facial features, and multiple congenital malformations (OMIM 269150). Refractory epilepsy is a common feature of SGS. Loss of function mutations have been typically associated with a distinct and milder phenotype characterized by intellectual disability and expressive speech impairment. Here we report three variants of SETBP1, two novel de novo truncating mutations, identified by NGS analysis of an Intellectual Disability gene panel in 600 subjects with non-specific neurodevelopmental disorders, and one missense identified by a developmental epilepsy gene panel tested in 56 pediatric epileptic cases. The three individuals carrying the identified SETBP1 variants presented mild to severe developmental delay and lacked the cardinal features of classical SGS. One of these subjects, carrying the c.1765C\>T (p.Arg589*) mutation, had mild Intellectual Disability with speech delay; the second one carrying the c.2199_2203del (p.Glu734Alafs19*) mutation had generalized epilepsy, responsive to treatment, and moderate Intellectual Disability; the third patient showed a severe cognitive defects and had a history of drug resistant epilepsy with West syndrome evolved into a Lennox-Gastaut syndrome. This latter subject carries the missense c.2572G\>A (p.Glu858Lys) variant, which is absent from the control population, reported as de novo in a subject with ASD, and located close to the SETBP1 hot spot for SGS-associated mutations. Our findings contribute to further characterizing the associated phenotypes and suggest inclusion of SETBP1 in the list of prioritized genes for the genetic diagnosis of overlapping phenotypes ranging from non-specific neurodevelopmental disorders to “developmental and epileptic encephalopathy” (DEE). © Copyright © 2020 Leonardi, Bettella, Pelizza, Aspromonte, Polli, Boniver, Sartori, Milani and Murgia.},

note = {Cited by: 15; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quaglia2020,

title = {Exploring Manually Curated Annotations of Intrinsically Disordered Proteins with DisProt},

author = {Federica Quaglia and Andr\'{a}s Hatos and Damiano Piovesan and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85092678821\&doi=10.100%2fcpbi.107\&partnerID=40\&md5=7352d90afb4ba69a521d424167263d8b},

doi = {10.1002/cpbi.107},

issn = {19343396},

year  = {2020},

date = {2020-01-01},

journal = {Current Protocols in Bioinformatics},

volume = {72},

number = {1},

publisher = {John Wiley and Sons Inc},

abstract = {DisProt is the major repository of manually curated data for intrinsically disordered proteins collected from the literature. Although lacking a stable tertiary structure under physiological conditions, intrinsically disordered proteins carry out a plethora of biological functions, some of them directly arising from their flexible nature. A growing number of scientific studies have been published during the last few decades in an effort to shed light on their unstructured state, their binding modes, and their functions. DisProt makes use of a team of expert biocurators to provide up-to-date annotations of intrinsically disordered proteins from the literature, making them available to the scientific community. Here we present a comprehensive description on how to use DisProt in different contexts and provide a detailed explanation of how to explore and interpret manually curated annotations of intrinsically disordered proteins. We describe how to search DisProt annotations, using both the web interface and the API for programmatic access. Finally, we explain how to visualize and interpret a DisProt entry, p53, a widely studied protein characterized by the presence of unstructured N-terminal and C-terminal regions. © 2020 Wiley Periodicals LLC. Basic Protocol 1: Performing a search in DisProt. Support Protocol 1: Downloading options. Support Protocol 2: Programmatic access with DisProt REST API. Basic Protocol 2: Visualizing and interpreting DisProt entries: the p53 use case. Basic Protocol 3: Providing feedback and submitting new intrinsic disorder−related data. © 2020 Wiley Periodicals LLC},

note = {Cited by: 2; All Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Leonardi2020b,

title = {A novel WAC loss of function mutation in an individual presenting with encephalopathy related to status epilepticus during sleep (ESES)},

author = {Emanuela Leonardi and Mariagrazia Bellini and Maria C. Aspromonte and Roberta Polli and Anna Mercante and Claudia Ciaccio and Elisa Granocchio and Elisa Bettella and Ilaria Donati and Elisa Cainelli and Stefania Boni and Stefano Sartori and Chiara Pantaleoni and Clementina Boniver and Alessandra Murgia},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85082481693\&doi=10.339%2fgenes11030344\&partnerID=40\&md5=e698d9eb8008cf9749e41d6bc1e55939},

doi = {10.3390/genes11030344},

issn = {20734425},

year  = {2020},

date = {2020-01-01},

journal = {Genes},

volume = {11},

number = {3},

publisher = {MDPI AG},

abstract = {WAC (WW Domain Containing Adaptor With Coiled-Coil) mutations have been reported in only 20 individuals presenting a neurodevelopmental disorder characterized by intellectual disability, neonatal hypotonia, behavioral problems, and mildly dysmorphic features. Using targeted deep sequencing, we screened a cohort of 630 individuals with variable degrees of intellectual disability and identified five WAC rare variants: two variants were inherited from healthy parents; two previously reported de novo mutations, c.1661_1664del (p.Ser554*) and c.374C\>A (p.Ser125*); and a novel c.381+2T\>C variant causing the skipping of exon 4 of the gene, inherited from a reportedly asymptomatic father with somatic mosaicism. A phenotypic evaluation of this individual evidenced areas of cognitive and behavioral deficits. The patient carrying the novel splicing mutation had a clinical history of encephalopathy related to status epilepticus during slow sleep (ESES), recently reported in another WAC individual. This first report of a WAC somatic mosaic remarks the contribution of mosaicism in the etiology of neurodevelopmental and neuropsychiatric disorders. We summarized the clinical data of reported individuals with WAC pathogenic mutations, which together with our findings, allowed for the expansion of the phenotypic spectrum of WAC-related disorders. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},

note = {Cited by: 13; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Monzon20201,

title = {Experimentally determined long intrinsically disordered protein regions are now abundant in the protein data bank},

author = {Alexander Miguel Monzon and Marco Necci and Federica Quaglia and Ian Walsh and Giuseppe Zanotti and Damiano Piovesan and Silvio C. E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85086855750\&doi=10.339%2fijms21124496\&partnerID=40\&md5=6683d73ab13066ab99fe00d4acdfbee8},

doi = {10.3390/ijms21124496},

issn = {16616596},

year  = {2020},

date = {2020-01-01},

journal = {International Journal of Molecular Sciences},

volume = {21},

number = {12},

pages = {1 \textendash 13},

publisher = {MDPI AG},

abstract = {Intrinsically disordered protein regions are commonly defined from missing electron density in X-ray structures. Experimental evidence for long disorder regions (LDRs) of at least 30 residues was so far limited to manually curated proteins. Here, we describe a comprehensive and large-scale analysis of experimental LDRs for 3133 unique proteins, demonstrating an increasing coverage of intrinsic disorder in the Protein Data Bank (PDB) in the last decade. The results suggest that long missing residue regions are a good quality source to annotate intrinsically disordered regions and perform functional analysis in large data sets. The consensus approach used to define LDRs allows to evaluate context dependent disorder and provide a common definition at the protein level. © 2020 by the authors. Licensee MDPI, Basel, Switzerland.},

note = {Cited by: 26; All Open Access, Gold Open Access, Green Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}