Emanuela Leonardi

@article{Aspromonte2024D434,

title = {DisProt in 2024: improving function annotation of intrinsically disordered proteins},

author = { Maria Cristina Aspromonte and Maria Victoria Nugnes and Federica Quaglia and Adel Bouharoua and Silvio C.E. Tosatto and Damiano Piovesan and Vasileios Sagris and Vasilis J. Promponas and Anastasia Chasapi and Erzs\'{e}bet Fich\'{o} and Galo E. Balatti and Gustavo Parisi and Mart\'{i}n Gonz\'{a}lez Buitr\'{o}n and Gabor Erdos and Matyas Pajkos and Zsuzsanna Doszt\'{a}nyi and Laszlo Dobson and Alessio Del Conte and Damiano Clementel and Edoardo Salladini and Emanuela Leonardi and Fatemeh Kordevani and Hamidreza Ghafouri and Luiggi G. Tenorio Ku and Alexander Miguel Monzon and Carlo Ferrari and Zs\'{o}fia K\'{a}lm\'{a}n and Juliet F. Nilsson and Jaime Santos and Carlos Pintado-Grima and Salvador Ventura and Veronika \'{A}cs and Rita Pancsa and Mariane Goncalves Kulik and Miguel A. Andrade-Navarro and Pedro Jos\'{e} Barbosa Pereira and Sonia Longhi and Philippe Le Mercier and Julian Bergier and Peter Tompa and Tamas Lazar},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85176208048\&doi=10.1093%2fnar%2fgkad928\&partnerID=40\&md5=fc34ce08667ff42029fdb54d5142c08f},

doi = {10.1093/nar/gkad928},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

abstract = {DisProt (URL: https://disprot.org) is the gold standard database for intrinsically disordered proteins and regions, providing valuable information about their functions. The latest version of DisProt brings significant advancements, including a broader representation of functions and an enhanced curation process. These improvements aim to increase both the quality of annotations and their coverage at the sequence level. Higher coverage has been achieved by adopting additional evidence codes. Quality of annotations has been improved by systematically applying Minimum Information About Disorder Experiments (MIADE) principles and reporting all the details of the experimental setup that could potentially influence the structural state of a protein. The DisProt database now includes new thematic datasets and has expanded the adoption of Gene Ontology terms, resulting in an extensive functional repertoire which is automatically propagated to UniProtKB. Finally, we show that DisProt’s curated annotations strongly correlate with disorder predictions inferred from AlphaFold2 pLDDT (predicted Local Distance Difference Test) confidence scores. This comparison highlights the utility of DisProt in explaining apparent uncertainty of certain well-defined predicted structures, which often correspond to folding-upon-binding fragments. Overall, DisProt serves as a comprehensive resource, combining experimental evidence of disorder information to enhance our understanding of intrinsically disordered proteins and their functional implications. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 10; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Quaglia2024,

title = {Best practices for the manual curation of intrinsically disordered proteins in DisProt},

author = { Federica Quaglia and Anastasia Chasapi and Maria Victoria Nugnes and Maria Cristina Aspromonte and Emanuela Leonardi and Damiano Piovesan and Silvio C.E. Tosatto},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85188297172\&doi=10.1093%2fdatabase%2fbaae009\&partnerID=40\&md5=df4fca19479789139b3fd19bb35c817f},

doi = {10.1093/database/baae009},

issn = {17580463},

year  = {2024},

date = {2024-01-01},

abstract = {The DisProt database is a resource containing manually curated data on experimentally validated intrinsically disordered proteins (IDPs) and intrinsically disordered regions (IDRs) from the literature. Developed in 2005, its primary goal was to collect structural and functional information into proteins that lack a fixed three-dimensional structure.Today, DisProt has evolved into a major repository that not only collects experimental data but also contributes to our understanding of the IDPs/IDRs roles in various biological processes, such as autophagy or the life cycle mechanisms in viruses or their involvement in diseases (such as cancer and neurodevelopmental disorders). DisProt offers detailed information on the structural states of IDPs/IDRs, including state transitions, interactions and their functions, all provided as curated annotations. One of the central activities of DisProt is the meticulous curation of experimental data from the literature. For this reason, to ensure that every expert and volunteer curator possesses the requisite knowledge for data evaluation, collection and integration, training courses and curation materials are available. However, biocuration guidelines concur on the importance of developing robust guidelines that not only provide critical information about data consistency but also ensure data acquisition.This guideline aims to provide both biocurators and external users with best practices for manually curating IDPs and IDRs in DisProt. It describes every step of the literature curation process and provides use cases of IDP curation within DisProt. © The Author(s) 2024. Published by Oxford University Press.},

note = {Cited by: 1; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Ghafouri2024D536,

title = {PED in 2024: improving the community deposition of structural ensembles for intrinsically disordered proteins},

author = { Hamidreza Ghafouri and Tamas Lazar and Alessio Del Conte and Luiggi G. Tenorio Ku and Peter Tompa and Silvio C.E. Tosatto and Alexander Miguel Monzon and Maria C. Aspromonte and Pau Bernad\'{o} and Bel\'{e}n Chaves-Arquero and Lucia Beatriz Chemes and Damiano Clementel and Tiago N. Cordeiro and Carlos A. Elena-Real and Michael Feig and Isabella C. Felli and Carlo Ferrari and Julie D. Forman-Kay and Tiago Gomes and Frank Gondelaud and Claudiu C. Gradinaru and T\^{a}p Ha-Duong and Teresa Head-Gordon and P\'{e}tur O. Heidarsson and Giacomo Janson and Gunnar Jeschke and Emanuela Leonardi and Zi Hao Liu and Sonia Longhi and Xamuel L. Lund and Maria J. Macias and Pau Martin-Malpartida and Davide Mercadante and Assia Mouhand and Gabor Nagy and Mar\'{i}a Victoria Nugnes and Jos\'{e} Manuel P\'{e}rez-Ca\~{n}adillas and Giulia Pesce and Roberta Pierattelli and Damiano Piovesan and Federica Quaglia and Sylvie Ricard-Blum and Paul Robustelli and Amin Sagar and Edoardo Salladini and Lucile S\'{e}nicourt and Nathalie Sibille and Jo\~{a}o M.C. Teixeira and Thomas E. Tsangaris and Mihaly Varadi},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85181761325\&doi=10.1093%2fnar%2fgkad947\&partnerID=40\&md5=0ad51562357f3e5f603d744e02f8729a},

doi = {10.1093/nar/gkad947},

issn = {03051048},

year  = {2024},

date = {2024-01-01},

abstract = {The Protein Ensemble Database (PED) (URL: https://proteinensemble.org) is the primary resource for depositing structural ensembles of intrinsically disordered proteins. This updated version of PED reflects advancements in the field, denoting a continual expansion with a total of 461 entries and 538 ensembles, including those generated without explicit experimental data through novel machine learning (ML) techniques. With this significant increment in the number of ensembles, a few yet-unprecedented new entries entered the database, including those also determined or refined by electron paramagnetic resonance or circular dichroism data. In addition, PED was enriched with several new features, including a novel deposition service, improved user interface, new database cross-referencing options and integration with the 3D-Beacons network\textemdashall representing efforts to improve the FAIRness of the database. Foreseeably, PED will keep growing in size and expanding with new types of ensembles generated by accurate and fast ML-based generative models and coarse-grained simulations. Therefore, among future efforts, priority will be given to further develop the database to be compatible with ensembles modeled at a coarse-grained level. © The Author(s) 2023. Published by Oxford University Press on behalf of Nucleic Acids Research.},

note = {Cited by: 10; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Gehin2023,

title = {CERT1 mutations perturb human development by disrupting sphingolipid homeostasis},

author = { Charlotte Gehin and Museer A. Lone and Winston Lee and Laura Capolupo and Sylvia Ho and Adekemi M. Adeyemi and Erica H. Gerkes and Alexander P.A. Stegmann and Estrella L\'{o}pez-Mart\'{i}n and Eva Bermejo-S\'{a}nchez and Beatriz Mart\'{i}nez-Delgado and Christiane Zweier and Cornelia Kraus and Bernt Popp and Vincent Strehlow and Daniel Gr\"{a}fe and Ina Knerr and Eppie R. Jones and Stefano Zamuner and Luciano A. Abriata and Vidya Kunnathully and Brandon E. Moeller and Anthony Vocat and Samuel Rommelaere and Jean-Philippe Bocquete and Evelyne Ruchti and Greta Limoni and Marine Van Campenhoudt and Samuel Bourgeat and Petra Henklein and Christian Gilissen and Bregje W. van Bon and Rolph Pfundt and Marjolein H. Willemsen and Jolanda H. Schieving and Emanuela Leonardi and Fiorenza Soli and Alessandra Murgia and Hui Guo and Qiumeng Zhang and Kun Xia and Christina R. Fagerberg and Christoph P. Beier and Martin J. Larsen and Irene Valenzuela and Paula Fern\'{a}ndez-\'{A}lvarez and Shiyi Xiong and Robert \'{S}migiel and Vanesa L\'{o}pez-Gonz\'{a}lez and Llu\'{i}s Armengol and Manuela Morleo and Angelo Selicorni and Annalaura Torella and Moira Blyth and Nicola S. Cooper and Valerie Wilson and Renske Oegema and Yvan Herenger and Aurore Garde and Ange-Line Bruel and Frederic Tran Mau-Them and Alexis B.R. Maddocks and Jennifer M. Bain and Musadiq A. Bhat and Gregory Costain and Peter Kannu and Ashish Marwaha and Neena L. Champaigne and Michael J. Friez and Ellen B. Richardson and Vykuntaraju K. Gowda and Varunvenkat M. Srinivasan and Yask Gupta and Tze Y. Lim and Simone Sanna-Cherchi and Bruno Lemaitre and Toshiyuki Yamaji and Kentaro Hanada and John E. Burke and Ana Marjia Jak\v{s}i\'{c} and Brian D. McCabe and Paolo De Los Rios and Thorsten Hornemann and Giovanni D’Angelo and Vincenzo A. Gennarino},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85159733545\&doi=10.1172%2fJCI165019\&partnerID=40\&md5=0f32fc96f0219379d9b830efbbbbefb6},

doi = {10.1172/JCI165019},

issn = {00219738},

year  = {2023},

date = {2023-01-01},

abstract = {Neural differentiation, synaptic transmission, and action potential propagation depend on membrane sphingolipids, whose metabolism is tightly regulated. Mutations in the ceramide transporter CERT (CERT1), which is involved in sphingolipid biosynthesis, are associated with intellectual disability, but the pathogenic mechanism remains obscure. Here, we characterize 31 individuals with de novo missense variants in CERT1. Several variants fall into a previously uncharacterized dimeric helical domain that enables CERT homeostatic inactivation, without which sphingolipid production goes unchecked. The clinical severity reflects the degree to which CERT autoregulation is disrupted, and inhibiting CERT pharmacologically corrects morphological and motor abnormalities in a Drosophila model of the disease, which we call ceramide transporter (CerTra) syndrome. These findings uncover a central role for CERT autoregulation in the control of sphingolipid biosynthetic flux, provide unexpected insight into the structural organization of CERT, and suggest a possible therapeutic approach for patients with CerTra syndrome. © 2023, Gehin et al.},

note = {Cited by: 11; All Open Access, Gold Open Access},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Vos2023351,

title = {DNA methylation episignatures are sensitive and specific biomarkers for detection of patients with KAT6A/KAT6B variants},

author = { Niels Vos and Jack Reilly and Mariet W Elting and Philippe M Campeau and David Coman and Zornitza Stark and Tiong Yang Tan and David J Amor and Simran Kaur and Miya Stjohn and Angela T Morgan and Benjamin A Kamien and Chirag Patel and Matthew L Tedder and Giuseppe Merla and Paolo Prontera and Marco Castori and Kai Muru and Felicity Collins and John Christodoulou and Janine Smith and Bruria Ben Zeev and Alessandra Murgia and Emanuela Leonardi and Natacha Esber and Antonio Martinez-Monseny and Didac Casas-Alba and Matthew Wallis and Marcel Mannens and Michael A Levy and Raissa Relator and Marielle Alders and Bekim Sadikovic},

url = {https://www.scopus.com/inward/record.uri?eid=2-s2.0-85160965403\&doi=10.2217%2fepi-2023-0079\&partnerID=40\&md5=5fb586acb83064545e1a62385bf47b83},

doi = {10.2217/epi-2023-0079},

issn = {17501911},

year  = {2023},

date = {2023-01-01},

abstract = {Accurate diagnosis for patients living with neurodevelopmental disorders is often met with numerous challenges, related to the ambiguity of findings and lack of specificity in genetic variants leading to pathology. Genome-wide DNA methylation analysis has been used to develop highly sensitive and specific 'episignatures' as biomarkers capable of differentiating and classifying complex neurodevelopmental disorders. In this study we describe distinct episignatures for KAT6A syndrome, caused by pathogenic variants in the lysine acetyltransferase A gene (KAT6A), and for the two neurodevelopmental disorders associated with lysine acetyl transferase B (KAT6B). We demonstrate the ability of our models to differentiate between highly overlapping episignatures, increasing the ability to effectively identify and diagnose these conditions. © 2023 Future Medicine Ltd.},

note = {Cited by: 2},

keywords = {},

pubstate = {published},

tppubtype = {article}

}