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2. The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Author

Zhou, Naihui, Jiang, Yuxiang, Bergquist, Timothy R, Lee, Alexandra J, Kacsoh, Balint Z, Crocker, Alex W, Lewis, Kimberley A, Georghiou, George, Nguyen, Huy N, Hamid, Md Nafiz, Davis, Larry, Dogan, Tunca, Atalay, Volkan, Rifaioglu, Ahmet S, Dalkıran, Alperen, Cetin Atalay, Rengul, Zhang, Chengxin, Hurto, Rebecca L, Freddolino, Peter L, Zhang, Yang, Bhat, Prajwal, Supek, Fran, Fernández, José M, Gemovic, Branislava, Perovic, Vladimir R, Davidović, Radoslav S, Sumonja, Neven, Veljkovic, Nevena, Asgari, Ehsaneddin, Mofrad, Mohammad RK, Profiti, Giuseppe, Savojardo, Castrense, Martelli, Pier Luigi, Casadio, Rita, Boecker, Florian, Schoof, Heiko, Kahanda, Indika, Thurlby, Natalie, McHardy, Alice C, Renaux, Alexandre, Saidi, Rabie, Gough, Julian, Freitas, Alex A, Antczak, Magdalena, Fabris, Fabio, Wass, Mark N, Hou, Jie, Cheng, Jianlin, Wang, Zheng, Romero, Alfonso E, Paccanaro, Alberto, Yang, Haixuan, Goldberg, Tatyana, Zhao, Chenguang, Holm, Liisa, Törönen, Petri, Medlar, Alan J, Zosa, Elaine, Borukhov, Itamar, Novikov, Ilya, Wilkins, Angela, Lichtarge, Olivier, Chi, Po-Han, Tseng, Wei-Cheng, Linial, Michal, Rose, Peter W, Dessimoz, Christophe, Vidulin, Vedrana, Dzeroski, Saso, Sillitoe, Ian, Das, Sayoni, Lees, Jonathan Gill, Jones, David T, Wan, Cen, Cozzetto, Domenico, Fa, Rui, Torres, Mateo, Warwick Vesztrocy, Alex, Rodriguez, Jose Manuel, Tress, Michael L, Frasca, Marco, Notaro, Marco, Grossi, Giuliano, Petrini, Alessandro, Re, Matteo, Valentini, Giorgio, Mesiti, Marco, Roche, Daniel B, Reeb, Jonas, Ritchie, David W, Aridhi, Sabeur, Alborzi, Seyed Ziaeddin, Devignes, Marie-Dominique, Koo, Da Chen Emily, Bonneau, Richard, Gligorijević, Vladimir, Barot, Meet, Fang, Hai, Toppo, Stefano, and Lavezzo, Enrico

Subjects
Human Genome, Networking and Information Technology R&D (NITRD), Genetics, Generic health relevance, Animals, Biofilms, Candida albicans, Drosophila melanogaster, Genome, Bacterial, Genome, Fungal, Humans, Locomotion, Memory, Long-Term, Molecular Sequence Annotation, Pseudomonas aeruginosa, Protein function prediction, Long-term memory, Biofilm, Critical assessment, Community challenge, Environmental Sciences, Biological Sciences, Information and Computing Sciences, Bioinformatics
Abstract

BackgroundThe Critical Assessment of Functional Annotation (CAFA) is an ongoing, global, community-driven effort to evaluate and improve the computational annotation of protein function.ResultsHere, we report on the results of the third CAFA challenge, CAFA3, that featured an expanded analysis over the previous CAFA rounds, both in terms of volume of data analyzed and the types of analysis performed. In a novel and major new development, computational predictions and assessment goals drove some of the experimental assays, resulting in new functional annotations for more than 1000 genes. Specifically, we performed experimental whole-genome mutation screening in Candida albicans and Pseudomonas aureginosa genomes, which provided us with genome-wide experimental data for genes associated with biofilm formation and motility. We further performed targeted assays on selected genes in Drosophila melanogaster, which we suspected of being involved in long-term memory.ConclusionWe conclude that while predictions of the molecular function and biological process annotations have slightly improved over time, those of the cellular component have not. Term-centric prediction of experimental annotations remains equally challenging; although the performance of the top methods is significantly better than the expectations set by baseline methods in C. albicans and D. melanogaster, it leaves considerable room and need for improvement. Finally, we report that the CAFA community now involves a broad range of participants with expertise in bioinformatics, biological experimentation, biocuration, and bio-ontologies, working together to improve functional annotation, computational function prediction, and our ability to manage big data in the era of large experimental screens.

Published
2019

3. Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

Author

Lavezzo, Enrico, Pacenti, Monia, Manuto, Laura, Boldrin, Caterina, Cattai, Margherita, Grazioli, Marco, Bianca, Federico, Sartori, Margherita, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Vanuzzo, Maria Cristina, Lisi, Vittoria, Antonello, Maria, Grimaldi, Carmela Ileana, Zulian, Chiara, Del Vecchio, Claudia, Plebani, Mario, Padoan, Andrea, Cirillo, Daniela Maria, Brazzale, Alessandra R., Tonon, Giovanni, Toppo, Stefano, Dorigatti, Ilaria, and Crisanti, Andrea

Published
2022
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5. An expanded evaluation of protein function prediction methods shows an improvement in accuracy

Author

Jiang, Yuxiang, Oron, Tal Ronnen, Clark, Wyatt T, Bankapur, Asma R, D'Andrea, Daniel, Lepore, Rosalba, Funk, Christopher S, Kahanda, Indika, Verspoor, Karin M, Ben-Hur, Asa, Koo, Emily, Penfold-Brown, Duncan, Shasha, Dennis, Youngs, Noah, Bonneau, Richard, Lin, Alexandra, Sahraeian, Sayed ME, Martelli, Pier Luigi, Profiti, Giuseppe, Casadio, Rita, Cao, Renzhi, Zhong, Zhaolong, Cheng, Jianlin, Altenhoff, Adrian, Skunca, Nives, Dessimoz, Christophe, Dogan, Tunca, Hakala, Kai, Kaewphan, Suwisa, Mehryary, Farrokh, Salakoski, Tapio, Ginter, Filip, Fang, Hai, Smithers, Ben, Oates, Matt, Gough, Julian, Törönen, Petri, Koskinen, Patrik, Holm, Liisa, Chen, Ching-Tai, Hsu, Wen-Lian, Bryson, Kevin, Cozzetto, Domenico, Minneci, Federico, Jones, David T, Chapman, Samuel, C., Dukka B K., Khan, Ishita K, Kihara, Daisuke, Ofer, Dan, Rappoport, Nadav, Stern, Amos, Cibrian-Uhalte, Elena, Denny, Paul, Foulger, Rebecca E, Hieta, Reija, Legge, Duncan, Lovering, Ruth C, Magrane, Michele, Melidoni, Anna N, Mutowo-Meullenet, Prudence, Pichler, Klemens, Shypitsyna, Aleksandra, Li, Biao, Zakeri, Pooya, ElShal, Sarah, Tranchevent, Léon-Charles, Das, Sayoni, Dawson, Natalie L, Lee, David, Lees, Jonathan G, Sillitoe, Ian, Bhat, Prajwal, Nepusz, Tamás, Romero, Alfonso E, Sasidharan, Rajkumar, Yang, Haixuan, Paccanaro, Alberto, Gillis, Jesse, Sedeño-Cortés, Adriana E, Pavlidis, Paul, Feng, Shou, Cejuela, Juan M, Goldberg, Tatyana, Hamp, Tobias, Richter, Lothar, Salamov, Asaf, Gabaldon, Toni, Marcet-Houben, Marina, Supek, Fran, Gong, Qingtian, Ning, Wei, Zhou, Yuanpeng, Tian, Weidong, Falda, Marco, Fontana, Paolo, Lavezzo, Enrico, Toppo, Stefano, Ferrari, Carlo, Giollo, Manuel, Piovesan, Damiano, Tosatto, Silvio, del Pozo, Angela, Fernández, José M, Maietta, Paolo, Valencia, Alfonso, Tress, Michael L, Benso, Alfredo, Di Carlo, Stefano, Politano, Gianfranco, Savino, Alessandro, Rehman, Hafeez Ur, Re, Matteo, Mesiti, Marco, Valentini, Giorgio, Bargsten, Joachim W, van Dijk, Aalt DJ, Gemovic, Branislava, Glisic, Sanja, Perovic, Vladmir, Veljkovic, Veljko, Veljkovic, Nevena, Almeida-e-Silva, Danillo C, Vencio, Ricardo ZN, Sharan, Malvika, Vogel, Jörg, Kansakar, Lakesh, Zhang, Shanshan, Vucetic, Slobodan, Wang, Zheng, Sternberg, Michael JE, Wass, Mark N, Huntley, Rachael P, Martin, Maria J, O'Donovan, Claire, Robinson, Peter N, Moreau, Yves, Tramontano, Anna, Babbitt, Patricia C, Brenner, Steven E, Linial, Michal, Orengo, Christine A, Rost, Burkhard, Greene, Casey S, Mooney, Sean D, Friedberg, Iddo, and Radivojac, Predrag

Subjects
Quantitative Biology - Quantitative Methods
Abstract

Background: The increasing volume and variety of genotypic and phenotypic data is a major defining characteristic of modern biomedical sciences. At the same time, the limitations in technology for generating data and the inherently stochastic nature of biomolecular events have led to the discrepancy between the volume of data and the amount of knowledge gleaned from it. A major bottleneck in our ability to understand the molecular underpinnings of life is the assignment of function to biological macromolecules, especially proteins. While molecular experiments provide the most reliable annotation of proteins, their relatively low throughput and restricted purview have led to an increasing role for computational function prediction. However, accurately assessing methods for protein function prediction and tracking progress in the field remain challenging. Methodology: We have conducted the second Critical Assessment of Functional Annotation (CAFA), a timed challenge to assess computational methods that automatically assign protein function. One hundred twenty-six methods from 56 research groups were evaluated for their ability to predict biological functions using the Gene Ontology and gene-disease associations using the Human Phenotype Ontology on a set of 3,681 proteins from 18 species. CAFA2 featured significantly expanded analysis compared with CAFA1, with regards to data set size, variety, and assessment metrics. To review progress in the field, the analysis also compared the best methods participating in CAFA1 to those of CAFA2. Conclusions: The top performing methods in CAFA2 outperformed the best methods from CAFA1, demonstrating that computational function prediction is improving. This increased accuracy can be attributed to the combined effect of the growing number of experimental annotations and improved methods for function prediction., Comment: Submitted to Genome Biology

Published
2016
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6. Immune System Deficiencies Do Not Alter SARS-CoV-2 Evolutionary Rate but Favour the Emergence of Mutations by Extending Viral Persistence

Author

Manuto, Laura, primary, Bado, Martina, additional, Cola, Marco, additional, Vanzo, Elena, additional, Antonello, Maria, additional, Mazzotti, Giorgia, additional, Pacenti, Monia, additional, Cordioli, Giampaolo, additional, Sasset, Lolita, additional, Cattelan, Anna Maria, additional, Toppo, Stefano, additional, and Lavezzo, Enrico, additional

Published
2024
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7. Author Correction: SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

Author

Dorigatti, Ilaria, Lavezzo, Enrico, Manuto, Laura, Ciavarella, Constanze, Pacenti, Monia, Boldrin, Caterina, Cattai, Margherita, Saluzzo, Francesca, Franchin, Elisa, Del Vecchio, Claudia, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Guglielmo, Simone, Fascina, Mariateresa, Grazioli, Marco, Alvisi, Gualtiero, Vanuzzo, Maria Cristina, Zupo, Tiziano, Calandrin, Reginetta, Lisi, Vittoria, Rossi, Lucia, Castagliuolo, Ignazio, Merigliano, Stefano, Unwin, H. Juliette T., Plebani, Mario, Padoan, Andrea, Brazzale, Alessandra R., Toppo, Stefano, Ferguson, Neil M., Donnelly, Christl A., and Crisanti, Andrea

Published
2021
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8. SARS-CoV-2 antibody dynamics and transmission from community-wide serological testing in the Italian municipality of Vo’

Author

Dorigatti, Ilaria, Lavezzo, Enrico, Manuto, Laura, Ciavarella, Constanze, Pacenti, Monia, Boldrin, Caterina, Cattai, Margherita, Saluzzo, Francesca, Franchin, Elisa, Del Vecchio, Claudia, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Guglielmo, Simone, Fascina, Mariateresa, Grazioli, Marco, Alvisi, Gualtiero, Vanuzzo, Maria Cristina, Zupo, Tiziano, Calandrin, Reginetta, Lisi, Vittoria, Rossi, Lucia, Castagliuolo, Ignazio, Merigliano, Stefano, Unwin, H. Juliette T., Plebani, Mario, Padoan, Andrea, Brazzale, Alessandra R., Toppo, Stefano, Ferguson, Neil M., Donnelly, Christl A., and Crisanti, Andrea

Published
2021
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9. A large-scale evaluation of computational protein function prediction

Author

Radivojac, Predrag, Clark, Wyatt T, Oron, Tal Ronnen, Schnoes, Alexandra M, Wittkop, Tobias, Sokolov, Artem, Graim, Kiley, Funk, Christopher, Verspoor, Karin, Ben-Hur, Asa, Pandey, Gaurav, Yunes, Jeffrey M, Talwalkar, Ameet S, Repo, Susanna, Souza, Michael L, Piovesan, Damiano, Casadio, Rita, Wang, Zheng, Cheng, Jianlin, Fang, Hai, Gough, Julian, Koskinen, Patrik, Törönen, Petri, Nokso-Koivisto, Jussi, Holm, Liisa, Cozzetto, Domenico, Buchan, Daniel WA, Bryson, Kevin, Jones, David T, Limaye, Bhakti, Inamdar, Harshal, Datta, Avik, Manjari, Sunitha K, Joshi, Rajendra, Chitale, Meghana, Kihara, Daisuke, Lisewski, Andreas M, Erdin, Serkan, Venner, Eric, Lichtarge, Olivier, Rentzsch, Robert, Yang, Haixuan, Romero, Alfonso E, Bhat, Prajwal, Paccanaro, Alberto, Hamp, Tobias, Kaßner, Rebecca, Seemayer, Stefan, Vicedo, Esmeralda, Schaefer, Christian, Achten, Dominik, Auer, Florian, Boehm, Ariane, Braun, Tatjana, Hecht, Maximilian, Heron, Mark, Hönigschmid, Peter, Hopf, Thomas A, Kaufmann, Stefanie, Kiening, Michael, Krompass, Denis, Landerer, Cedric, Mahlich, Yannick, Roos, Manfred, Björne, Jari, Salakoski, Tapio, Wong, Andrew, Shatkay, Hagit, Gatzmann, Fanny, Sommer, Ingolf, Wass, Mark N, Sternberg, Michael JE, Škunca, Nives, Supek, Fran, Bošnjak, Matko, Panov, Panče, Džeroski, Sašo, Šmuc, Tomislav, Kourmpetis, Yiannis AI, van Dijk, Aalt DJ, Braak, Cajo JF ter, Zhou, Yuanpeng, Gong, Qingtian, Dong, Xinran, Tian, Weidong, Falda, Marco, Fontana, Paolo, Lavezzo, Enrico, Di Camillo, Barbara, Toppo, Stefano, Lan, Liang, Djuric, Nemanja, Guo, Yuhong, Vucetic, Slobodan, Bairoch, Amos, Linial, Michal, Babbitt, Patricia C, Brenner, Steven E, Orengo, Christine, and Rost, Burkhard

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Algorithms, Animals, Computational Biology, Databases, Protein, Exoribonucleases, Forecasting, Humans, Molecular Biology, Molecular Sequence Annotation, Proteins, Species Specificity, Technology, Medical and Health Sciences, Developmental Biology, Biological sciences
Abstract

Automated annotation of protein function is challenging. As the number of sequenced genomes rapidly grows, the overwhelming majority of protein products can only be annotated computationally. If computational predictions are to be relied upon, it is crucial that the accuracy of these methods be high. Here we report the results from the first large-scale community-based critical assessment of protein function annotation (CAFA) experiment. Fifty-four methods representing the state of the art for protein function prediction were evaluated on a target set of 866 proteins from 11 organisms. Two findings stand out: (i) today's best protein function prediction algorithms substantially outperform widely used first-generation methods, with large gains on all types of targets; and (ii) although the top methods perform well enough to guide experiments, there is considerable need for improvement of currently available tools.

Published
2013

11. A comparative analysis of polyomaviruses Large Tumor Antigens reveals evolution of different importin α-dependent nuclear localization signals

Author

Alvisi, Gualtiero, primary, Cross, Emily, additional, Akbari, Nasim, additional, Ghassabian, Hanieh, additional, Hoad, Mikayla, additional, Pavan, Silvia, additional, Ariawan, Daryl, additional, Donnelly, Camilla, additional, Lavezzo, Enrico, additional, Petersen, Gayle, additional, and Forwood, Jade, additional

Published
2023
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13. A functional and structural comparative analysis of large tumor antigens reveals evolution of different importin α‐dependent nuclear localization signals.

Author

Cross, Emily M., Akbari, Nasim, Ghassabian, Hanieh, Hoad, Mikayla, Pavan, Silvia, Ariawan, Daryl, Donnelly, Camilla M., Lavezzo, Enrico, Petersen, Gayle F., Forwood, Jade K., and Alvisi, Gualtiero

Abstract

Nucleocytoplasmic transport regulates the passage of proteins between the nucleus and cytoplasm. In the best characterized pathway, importin (IMP) α bridges cargoes bearing basic, classical nuclear localization signals (cNLSs) to IMPβ1, which mediates transport through the nuclear pore complex. IMPα recognizes three types of cNLSs via two binding sites: the major binding site accommodates monopartite cNLSs, the minor binding site recognizes atypical cNLSs, while bipartite cNLSs simultaneously interact with both major and minor sites. Despite the growing knowledge regarding IMPα‐cNLS interactions, our understanding of the evolution of cNLSs is limited. We combined bioinformatic, biochemical, functional, and structural approaches to study this phenomenon, using polyomaviruses (PyVs) large tumor antigens (LTAs) as a model. We characterized functional cNLSs from all human (H)PyV LTAs, located between the LXCXE motif and origin binding domain. Surprisingly, the prototypical SV40 monopartite NLS is not well conserved; HPyV LTA NLSs are extremely heterogenous in terms of structural organization, IMPα isoform binding, and nuclear targeting abilities, thus influencing the nuclear accumulation properties of full‐length proteins. While several LTAs possess bipartite cNLSs, merkel cell PyV contains a hybrid bipartite cNLS whose upstream stretch of basic amino acids can function as an atypical cNLS, specifically binding to the IMPα minor site upon deletion of the downstream amino acids after viral integration in the host genome. Therefore, duplication of a monopartite cNLS and subsequent accumulation of point mutations, optimizing interaction with distinct IMPα binding sites, led to the evolution of bipartite and atypical NLSs binding at the minor site. [ABSTRACT FROM AUTHOR]

Published
2024
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16. Role of the Extracytoplasmic Function Sigma Factor SigE in the Stringent Response of Mycobacterium tuberculosis

Author

Baruzzo, Giacomo, primary, Serafini, Agnese, additional, Finotello, Francesca, additional, Sanavia, Tiziana, additional, Cioetto-Mazzabò, Laura, additional, Boldrin, Francesca, additional, Lavezzo, Enrico, additional, Barzon, Luisa, additional, Toppo, Stefano, additional, Provvedi, Roberta, additional, Manganelli, Riccardo, additional, and Di Camillo, Barbara, additional

Published
2023
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20. Prospective epidemiological, molecular, and genetic characterization of a novel coronavirus disease in the Val Venosta/Vinschgau : the CHRIS COVID-19 study protocol

Author

Pattaro, Cristian, Barbieri, Giulia, Foco, Luisa, Weichenberger, Christian X., Biasiotto, Roberta, De Grandi, Alessandro, Fuchsberger, Christian, Egger, Clemens, Amon, Vera S. C., Hicks, Andrew A., Mian, Michael, Mahlknecht, Angelika, Lombardo, Stefano, Meier, Horand, Weiss, Helmuth, Rainer, Robert, Dejaco, Christian, Weiss, Günter, Lavezzo, Enrico, Crisanti, Andrea, Pizzato, Massimo, Domingues, Francisco S., Mascalzoni, Deborah, Gögele, Martin, Melotti, Roberto, Pramstaller, Peter P., Pattaro, Cristian, Barbieri, Giulia, Foco, Luisa, Weichenberger, Christian X., Biasiotto, Roberta, De Grandi, Alessandro, Fuchsberger, Christian, Egger, Clemens, Amon, Vera S. C., Hicks, Andrew A., Mian, Michael, Mahlknecht, Angelika, Lombardo, Stefano, Meier, Horand, Weiss, Helmuth, Rainer, Robert, Dejaco, Christian, Weiss, Günter, Lavezzo, Enrico, Crisanti, Andrea, Pizzato, Massimo, Domingues, Francisco S., Mascalzoni, Deborah, Gögele, Martin, Melotti, Roberto, and Pramstaller, Peter P.

Abstract

The COVID-19 pandemic has been threatening the healthcare and socioeconomic systems of entire nations. While population-based surveys to assess the distribution of SARS-CoV-2 infection have become a priority, pre-existing longitudinal studies are ideally suited to assess the determinants of COVID-19 onset and severity.The Cooperative Health Research In South Tyrol (CHRIS) study completed the baseline recruitment of 13,393 adults from the Venosta/Vinschgau rural district in 2018, collecting extensive phenotypic and biomarker data, metabolomic data, densely imputed genotype and whole-exome sequencing data.Based on CHRIS, we designed a prospective study, called CHRIS COVID-19, aimed at: 1) estimating the incidence of SARS-CoV-2 infections; 2) screening for and investigating the determinants of incident infection among CHRIS participants and their household members; 3) monitoring the immune response of infected participants prospectively.An online screening questionnaire was sent to all CHRIS participants and their household members. A random sample of 1450 participants representative of the district population was invited to assess active (nasopharyngeal swab) or past (serum antibody test) infections. We prospectively invited for complete SARS-CoV-2 testing all questionnaire completers gauged as possible cases of past infection and their household members. In positive tested individuals, antibody response is monitored quarterly for one year. Untested and negative participants receive the screening questionnaire every four weeks until gauged as possible incident cases or till the study end.Originated from a collaboration between researchers and community stakeholders, the CHRIS COVID-19 study aims at generating knowledge about the epidemiological, molecular, and genetic characterization of COVID-19 and its long-term sequelae.

Published
2022
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22. Longitudinal analysis of T cell receptor repertoires reveals shared patterns of antigen-specific response to SARS-CoV-2 infection

Author

Gittelman, Rachel M., primary, Lavezzo, Enrico, additional, Snyder, Thomas M., additional, Zahid, H. Jabran, additional, Carty, Cara L., additional, Elyanow, Rebecca, additional, Dalai, Sudeb, additional, Kirsch, Ilan, additional, Baldo, Lance, additional, Manuto, Laura, additional, Franchin, Elisa, additional, Del Vecchio, Claudia, additional, Pacenti, Monia, additional, Boldrin, Caterina, additional, Cattai, Margherita, additional, Saluzzo, Francesca, additional, Padoan, Andrea, additional, Plebani, Mario, additional, Simeoni, Fabio, additional, Bordini, Jessica, additional, Lorè, Nicola I., additional, Lazarević, Dejan, additional, Cirillo, Daniela M., additional, Ghia, Paolo, additional, Toppo, Stefano, additional, Carlson, Jonathan M., additional, Robins, Harlan S., additional, Crisanti, Andrea, additional, and Tonon, Giovanni, additional

Published
2022
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23. Additional file 1 of Neutralising reactivity against SARS-CoV-2 Delta and Omicron variants by vaccination and infection history

Author

Lavezzo, Enrico, Pacenti, Monia, Manuto, Laura, Boldrin, Caterina, Cattai, Margherita, Grazioli, Marco, Bianca, Federico, Sartori, Margherita, Caldart, Federico, Castelli, Gioele, Nicoletti, Michele, Nieddu, Eleonora, Salvadoretti, Elisa, Labella, Beatrice, Fava, Ludovico, Vanuzzo, Maria Cristina, Lisi, Vittoria, Antonello, Maria, Grimaldi, Carmela Ileana, Zulian, Chiara, Del Vecchio, Claudia, Plebani, Mario, Padoan, Andrea, Cirillo, Daniela Maria, Brazzale, Alessandra R., Tonon, Giovanni, Toppo, Stefano, Dorigatti, Ilaria, and Crisanti, Andrea

Abstract

Additional file 1: Figure S1. Anti-N antibody titres and dynamics in vaccinated and unvaccinated subjects; Figure S2. Anti-N antibody titres of vaccinated and unvaccinated individuals previously exposed to SARS-CoV-2 infection differ according to age; Figure S3. Correlation among DiaSorin S1/S2, DiaSorin trimeric tests and neutralisation assay; Figure S4. Features of the cohorts analysed in this study. Table S1. Concordance between S1/S2 and trimericS DiaSorin assays.

Published
2022
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25. Phylogeography and genomic epidemiology of SARS-CoV-2 in Italy and Europe with newly characterized Italian genomes between February-June 2020

Author

Lai, Alessia, Bergna, Annalisa, Toppo, Stefano, Morganti, Marina, Menzo, Stefano, Ghisetti, Valeria, Bruzzone, Bianca, Codeluppi, Mauro, Fiore, Vito, Rullo, Emmanuele Venanzi, Antonelli, Guido, Sarmati, Loredana, Brindicci, Gaetano, Callegaro, Annapaola, Sagnelli, Caterina, Francisci, Daniela, Vicenti, Ilaria, Miola, Arianna, Tonon, Giovanni, Cirillo, Daniela, Menozzi, Ilaria, Caucci, Sara, Cerutti, Francesco, Orsi, Andrea, Schiavo, Roberta, Babudieri, Sergio, Nunnari, Giuseppe, Mastroianni, Claudio M., Andreoni, Massimo, Monno, Laura, Guarneri, Davide, Coppola, Nicola, Crisanti, Andrea, Galli, Massimo, Zehender, Gianguglielmo, Balotta, Claudia, Ventura, Carla della, Schiuma, Marco, Lavezzo, Enrico, Fontana, Paolo, Bianco, Luca, Bertolotti, Luigi, Manuto, Laura, Grazioli, Marco, Bianca, Federico, Del Vecchio, Claudia, Franchin, Elisa, Onelia, Francesco, Spitaleri, Andrea, Saluzzo, Francesca, Lorenzin, Giovanni, Pongolini, Stefano, Scaltriti, Erika, Soliani, Laura, Bagnarelli, Patrizia, Turchi, Chiara, Onofri, Valerio, Melchionda, Filomena, Tagliabracci, Adriano, Burdino, Elisa, Milia, Maria Grazia, Caligiuri, Patrizia, De Pace, Vanessa, Ricucci, Valentina, Domnich, Alexander, Boccotti, Simona, Cristina, Leoni Maria, Cascio, Giuliana Lo, Rubino, Salvatore, Lai, Vincenzo, Rocca, Giulia, Govoni, Rosalba, Mancuso, Giuseppe, Campagna, Roberta, Mazzuti, Laura, Oliveto, Giuseppe, Turriziani, Ombretta, Campogiani, Laura, Compagno, Mirko, Coppola, Luigi, Crea, Angela Maria Antonia, De Simone, Giuseppe, Di Lorenzo, Andrea, Ferrari, Ludovica, Iannetta, Marco, Malagnino, Vincenzo, Mulas, Tiziana, Rossi, Benedetta, Spalliera, Ilaria, Tedde, Simona, Teti, Elisabetta, Vitale, Pietro, Zordan, Marta, Milano, Eugenio, Lagioia, Antonella, Gallitelli, Rosa, Starace, Mario, Minichini, Carmine, Di Fraia, Alessia, Schioppa, Maddalena, Greco, Rita, Gidari, Anna, Zazzi, Maurizio, Dragoni, Filippo, Puma, Laura Li, Ronchiadin, Silvia, Ruggerone, Luigi, Russignaga, Dario, Lai, Alessia, Bergna, Annalisa, Toppo, Stefano, Morganti, Marina, Menzo, Stefano, Ghisetti, Valeria, Bruzzone, Bianca, Codeluppi, Mauro, Fiore, Vito, Rullo, Emmanuele Venanzi, Antonelli, Guido, Sarmati, Loredana, Brindicci, Gaetano, Callegaro, Annapaola, Sagnelli, Caterina, Francisci, Daniela, Vicenti, Ilaria, Miola, Arianna, Tonon, Giovanni, Cirillo, Daniela, Menozzi, Ilaria, Caucci, Sara, Cerutti, Francesco, Orsi, Andrea, Schiavo, Roberta, Babudieri, Sergio, Nunnari, Giuseppe, Mastroianni, Claudio M, Andreoni, Massimo, Monno, Laura, Guarneri, Davide, Coppola, Nicola, Crisanti, Andrea, Galli, Massimo, and Zehender, Gianguglielmo

Subjects
Europe, Phylogeography, Genome, Italy, SARS-CoV-2, Communicable Disease Control, Humans, COVID-19, Genome, Viral, Viral, Settore MED/17, Human
Abstract

The aims of this study were to characterize new SARS-CoV-2 genomes sampled all over Italy and to reconstruct the origin and the evolutionary dynamics in Italy and Europe between February and June 2020. The cluster analysis showed only small clusters including < 80 Italian isolates, while most of the Italian strains were intermixed in the whole tree. Pure Italian clusters were observed mainly after the lockdown and distancing measures were adopted. Lineage B and B.1 spread between late January and early February 2020, from China to Veneto and Lombardy, respectively. Lineage B.1.1 (20B) most probably evolved within Italy and spread from central to south Italian regions, and to European countries. The lineage B.1.1.1 (20D) developed most probably in other European countries entering Italy only in the second half of March and remained localized in Piedmont until June 2020. In conclusion, within the limitations of phylogeographical reconstruction, the estimated ancestral scenario suggests an important role of China and Italy in the widespread diffusion of the D614G variant in Europe in the early phase of the pandemic and more dispersed exchanges involving several European countries from the second half of March 2020.

Published
2022

27. Impact of antigen test target failure and testing strategies on the transmission of SARS-CoV-2 variants

Author

Vecchio, Claudia Del, primary, Daniels, Bethan Cracknell, additional, Brancaccio, Giuseppina, additional, Brazzale, Alessandra, additional, Lavezzo, Enrico, additional, Ciavarella, Constanze, additional, Onelia, Francesco, additional, Franchin, Elisa, additional, Manuto, Laura, additional, Bianca, Federico, additional, Cianci, Vito, additional, Cattelan, Annamaria, additional, Dorigatti, Ilaria, additional, Toppo, Stefano, additional, and Crisanti, Andrea, additional

Published
2022
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28. Rapid SARS-CoV-2 Intra-Host and Within-Household Emergence of Novel Haplotypes

Author

Manuto, Laura, primary, Grazioli, Marco, additional, Spitaleri, Andrea, additional, Fontana, Paolo, additional, Bianco, Luca, additional, Bertolotti, Luigi, additional, Bado, Martina, additional, Mazzotti, Giorgia, additional, Bianca, Federico, additional, Onelia, Francesco, additional, Lorenzin, Giovanni, additional, Simeoni, Fabio, additional, Lazarevic, Dejan, additional, Franchin, Elisa, additional, Vecchio, Claudia Del, additional, Dorigatti, Ilaria, additional, Tonon, Giovanni, additional, Cirillo, Daniela Maria, additional, Lavezzo, Enrico, additional, Crisanti, Andrea, additional, and Toppo, Stefano, additional

Published
2022
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29. Rapid longitudinal SARS-CoV-2 intra-host emergence of novel haplotypes regardless of immune deficiencies

Author

Manuto, Laura, primary, Grazioli, Marco, additional, Spitaleri, Andrea, additional, Fontana, Paolo, additional, Bianco, Luca, additional, Bertolotti, Luigi, additional, Bado, Martina, additional, Mazzotti, Giorgia, additional, Bianca, Federico, additional, Onelia, Francesco, additional, Lorenzin, Giovanni, additional, Simeoni, Fabio, additional, Lazarevic, Dejan, additional, Franchin, Elisa, additional, Del Vecchio, Claudia, additional, Dorigatti, Ilaria, additional, Tonon, Giovanni, additional, Cirillo, daniela, additional, Lavezzo, Enrico, additional, Crisanti, Andrea, additional, and Toppo, Stefano, additional

Published
2021
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30. Neutralising reactivity against SARS-CoV-2 B.1.617.2 (Delta) variant by vaccination status and pre-exposure

Author

Lavezzo, Enrico, primary, Pacenti, Monia, additional, Manuto, Laura, additional, Boldrin, Caterina, additional, Cattai, Margherita, additional, Grazioli, Marco, additional, Bianca, Federico, additional, Sartori, Margherita, additional, Caldart, Federico, additional, Castelli, Gioele, additional, Nicoletti, Michele, additional, Nieddu, Eleonora, additional, Salvadoretti, Elisa, additional, Labella, Beatrice, additional, Fava, Ludovico, additional, Vanuzzo, Maria, additional, Lisi, Vittoria, additional, Antonello, Maria, additional, Grimaldi, Carmela, additional, Zulian, Chiara, additional, Vecchio, Claudia Del, additional, Plebani, Mario, additional, Padoan, Andrea, additional, Cirillo, Daniela Maria, additional, Brazzale, Alessandra, additional, Tonon, Giovanni, additional, Toppo, Stefano, additional, Dorigatti, laria, additional, and Crisanti, Andrea, additional

Published
2021
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31. Prospective epidemiological, molecular, and genetic characterization of a novel coronavirus disease in the Val Venosta/Vinschgau: the CHRIS COVID-19 study protocol

Author

Pattaro, Cristian, primary, Barbieri, Giulia, additional, Foco, Luisa, additional, Weichenberger, Christian X., additional, Biasiotto, Roberta, additional, De Grandi, Alessandro, additional, Fuchsberger, Christian, additional, Egger, Clemens, additional, Amon, Vera S. C., additional, Hicks, Andrew A., additional, Mian, Michael, additional, Mahlknecht, Angelika, additional, Lombardo, Stefano, additional, Meier, Horand, additional, Weiss, Helmuth, additional, Rainer, Robert, additional, Dejaco, Christian, additional, Weiss, Günter, additional, Lavezzo, Enrico, additional, Crisanti, Andrea, additional, Pizzato, Massimo, additional, Domingues, Francisco S., additional, Mascalzoni, Deborah, additional, Gögele, Martin, additional, Melotti, Roberto, additional, and Pramstaller, Peter P., additional

Published
2021
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33. Disease Severity and Prognosis of SARS-CoV-2 Infection in Hospitalized Patients Is Not Associated With Viral Load in Nasopharyngeal Swab

Author

Cocconcelli, Elisabetta, primary, Castelli, Gioele, additional, Onelia, Francesco, additional, Lavezzo, Enrico, additional, Giraudo, Chiara, additional, Bernardinello, Nicol, additional, Fichera, Giulia, additional, Leoni, Davide, additional, Trevenzoli, Marco, additional, Saetta, Marina, additional, Cattelan, Annamaria, additional, Crisanti, Andrea, additional, Spagnolo, Paolo, additional, and Balestro, Elisabetta, additional

Published
2021
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34. Prospective epidemiological, molecular, and genetic characterization of a novel coronavirus disease in the Val Venosta/Vinschgau : the CHRIS COVID-19 study protocol

Author

Pattaro, Cristian, Barbieri, Giulia, Foco, Luisa, Weichenberger, Christian X., Biasiotto, Roberta, De Grandi, Alessandro, Fuchsberger, Christian, Egger, Clemens, Amon, Vera S. C., Hicks, Andrew A., Mian, Michael, Mahlknecht, Angelika, Lombardo, Stefano, Meier, Horand, Weiss, Helmuth, Rainer, Robert, Dejaco, Christian, Weiss, Günter, Lavezzo, Enrico, Crisanti, Andrea, Pizzato, Massimo, Domingues, Francisco S., Mascalzoni, Deborah, Gögele, Martin, Melotti, Roberto, Pramstaller, Peter P., Pattaro, Cristian, Barbieri, Giulia, Foco, Luisa, Weichenberger, Christian X., Biasiotto, Roberta, De Grandi, Alessandro, Fuchsberger, Christian, Egger, Clemens, Amon, Vera S. C., Hicks, Andrew A., Mian, Michael, Mahlknecht, Angelika, Lombardo, Stefano, Meier, Horand, Weiss, Helmuth, Rainer, Robert, Dejaco, Christian, Weiss, Günter, Lavezzo, Enrico, Crisanti, Andrea, Pizzato, Massimo, Domingues, Francisco S., Mascalzoni, Deborah, Gögele, Martin, Melotti, Roberto, and Pramstaller, Peter P.

Abstract

The COVID-19 pandemic has been threatening the healthcare and socioeconomic systems of entire nations. While population-based surveys to assess the distribution of SARS-CoV-2 infection have become a priority, pre-existing longitudinal studies are ideally suited to assess the determinants of COVID-19 onset and severity.The Cooperative Health Research In South Tyrol (CHRIS) study completed the baseline recruitment of 13,393 adults from the Venosta/Vinschgau rural district in 2018, collecting extensive phenotypic and biomarker data, metabolomic data, densely imputed genotype and whole-exome sequencing data.Based on CHRIS, we designed a prospective study, called CHRIS COVID-19, aimed at: 1) estimating the incidence of SARS-CoV-2 infections; 2) screening for and investigating the determinants of incident infection among CHRIS participants and their household members; 3) monitoring the immune response of infected participants prospectively.An online screening questionnaire was sent to all CHRIS participants and their household members. A random sample of 1450 participants representative of the district population was invited to assess active (nasopharyngeal swab) or past (serum antibody test) infections. We prospectively invited for complete SARS-CoV-2 testing all questionnaire completers gauged as possible cases of past infection and their household members. In positive tested individuals, antibody response is monitored quarterly for one year. Untested and negative participants receive the screening questionnaire every four weeks until gauged as possible incident cases or till the study end.Originated from a collaboration between researchers and community stakeholders, the CHRIS COVID-19 study aims at generating knowledge about the epidemiological, molecular, and genetic characterization of COVID-19 and its long-term sequelae.

Published
2021
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37. Suppression of a SARS-CoV-2 outbreak in the Italian municipality of Vo’

Author

Lavezzo, Enrico, Franchin, Elisa, Ciavarella, Constanze, Cuomo-Dannenburg, Gina, Barzon, Luisa, Del Vecchio, Claudia, Rossi, Lucia, Manganelli, Riccardo, Loregian, Arianna, Navarin, Nicolò, Abate, Davide, Sciro, Manuela, Merigliano, Stefano, De Canale, Ettore, Vanuzzo, Maria Cristina, Besutti, Valeria, Saluzzo, Francesca, Onelia, Francesco, Pacenti, Monia, Parisi, Saverio G., Carretta, Giovanni, Donato, Daniele, Flor, Luciano, Cocchio, Silvia, Masi, Giulia, Sperduti, Alessandro, Cattarino, Lorenzo, Salvador, Renato, Nicoletti, Michele, Caldart, Federico, Castelli, Gioele, Nieddu, Eleonora, Labella, Beatrice, Fava, Ludovico, Drigo, Matteo, Gaythorpe, Katy A. M., Brazzale, Alessandra R., Toppo, Stefano, Trevisan, Marta, Baldo, Vincenzo, Donnelly, Christl A., Ferguson, Neil M., Dorigatti, Ilaria, Crisanti, Andrea, Ainslie, Kylie E. C., Baguelin, Marc, Bhatt, Samir, Boonyasiri, Adhiratha, Boyd, Olivia, Coupland, Helen L., Cucunubá, Zulma, Djafaara, Bimandra A., van Elsland, Sabine L., FitzJohn, Rich, Flaxman, Seth, Green, Will D., Hallett, Timothy, Hamlet, Arran, Haw, David, Imai, Natsuko, Jeffrey, Benjamin, Knock, Edward, Laydon, Daniel J., Mellan, Thomas, Mishra, Swapnil, Nedjati-Gilani, Gemma, Nouvellet, Pierre, Okell, Lucy C., Parag, Kris V., Riley, Steven, Thompson, Hayley A., Unwin, H. Juliette T., Verity, Robert, Vollmer, Michaela A. C., Walker, Patrick G. T., Walters, Caroline E., Wang, Haowei, Wang, Yuanrong, Watson, Oliver J., Whittaker, Charles, Whittles, Lilith K., Xi, Xiaoyue, Medical Research Council (MRC), Medical Research Council, The Royal Society, Bill & Melinda Gates Foundation, Imperial College Healthcare NHS Trust- BRC Funding, The Academy of Medical Sciences, National Institute for Health Research, UK Research and Innovation, and Wellcome Trust

Subjects
0301 basic medicine, Male, CORONAVIRUS, Viral Nonstructural Proteins, medicine.disease_cause, Disease Outbreaks, 0302 clinical medicine, Viral Envelope Proteins, Prevalence, 030212 general & internal medicine, Child, Asymptomatic Infections, Coronavirus, Aged, 80 and over, education.field_of_study, Coronavirus RNA-Dependent RNA Polymerase, Multidisciplinary, Middle Aged, Viral Load, 3. Good health, Multidisciplinary Sciences, Policy, Italy, Child, Preschool, Science & Technology - Other Topics, Female, medicine.symptom, Coronavirus Infections, Viral load, Serial interval, Adult, medicine.medical_specialty, Adolescent, General Science & Technology, Population, Pneumonia, Viral, Policy and public health in microbiology, Asymptomatic, 03 medical and health sciences, Betacoronavirus, Coronavirus Envelope Proteins, Young Adult, Internal medicine, medicine, Imperial College COVID-19 Response Team, Humans, Author Correction, education, Pandemics, Aged, Science & Technology, business.industry, SARS-CoV-2, Infant, Newborn, Outbreak, COVID-19, Infant, medicine.disease, RNA-Dependent RNA Polymerase, Confidence interval, Pneumonia, 030104 developmental biology, business
Abstract

On 21 February 2020, a resident of the municipality of Vo', a small town near Padua (Italy), died of pneumonia due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection1. This was the first coronavirus disease 19 (COVID-19)-related death detected in Italy since the detection of SARS-CoV-2 in the Chinese city of Wuhan, Hubei province2. In response, the regional authorities imposed the lockdown of the whole municipality for 14 days3. Here we collected information on the demography, clinical presentation, hospitalization, contact network and the presence of SARS-CoV-2 infection in nasopharyngeal swabs for 85.9% and 71.5% of the population of Vo' at two consecutive time points. From the first survey, which was conducted around the time the town lockdown started, we found a prevalence of infection of 2.6% (95% confidence interval (CI): 2.1-3.3%). From the second survey, which was conducted at the end of the lockdown, we found a prevalence of 1.2% (95% CI: 0.8-1.8%). Notably, 42.5% (95% CI: 31.5-54.6%) of the confirmed SARS-CoV-2 infections detected across the two surveys were asymptomatic (that is, did not have symptoms at the time of swab testing and did not develop symptoms afterwards). The mean serial interval was 7.2 days (95% CI: 5.9-9.6). We found no statistically significant difference in the viral load of symptomatic versus asymptomatic infections (P = 0.62 and 0.74 for E and RdRp genes, respectively, exact Wilcoxon-Mann-Whitney test). This study sheds light on the frequency of asymptomatic SARS-CoV-2 infection, their infectivity (as measured by the viral load) and provides insights into its transmission dynamics and the efficacy of the implemented control measures.

Published
2020
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38. Argot2: a large scale function prediction tool relying on semantic similarity of weighted Gene Ontology terms

Author

Falda Marco, Toppo Stefano, Pescarolo Alessandro, Lavezzo Enrico, Di Camillo Barbara, Facchinetti Andrea, Cilia Elisa, Velasco Riccardo, and Fontana Paolo

Subjects
Computer applications to medicine. Medical informatics, R858-859.7, Biology (General), QH301-705.5
Abstract

Abstract Background Predicting protein function has become increasingly demanding in the era of next generation sequencing technology. The task to assign a curator-reviewed function to every single sequence is impracticable. Bioinformatics tools, easy to use and able to provide automatic and reliable annotations at a genomic scale, are necessary and urgent. In this scenario, the Gene Ontology has provided the means to standardize the annotation classification with a structured vocabulary which can be easily exploited by computational methods. Results Argot2 is a web-based function prediction tool able to annotate nucleic or protein sequences from small datasets up to entire genomes. It accepts as input a list of sequences in FASTA format, which are processed using BLAST and HMMER searches vs UniProKB and Pfam databases respectively; these sequences are then annotated with GO terms retrieved from the UniProtKB-GOA database and the terms are weighted using the e-values from BLAST and HMMER. The weighted GO terms are processed according to both their semantic similarity relations described by the Gene Ontology and their associated score. The algorithm is based on the original idea developed in a previous tool called Argot. The entire engine has been completely rewritten to improve both accuracy and computational efficiency, thus allowing for the annotation of complete genomes. Conclusions The revised algorithm has been already employed and successfully tested during in-house genome projects of grape and apple, and has proven to have a high precision and recall in all our benchmark conditions. It has also been successfully compared with Blast2GO, one of the methods most commonly employed for sequence annotation. The server is freely accessible at http://www.medcomp.medicina.unipd.it/Argot2.

Published
2012
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39. Emergence of N antigen SARS-CoV-2 genetic variants escaping detection of antigenic tests

Author

Del Vecchio, Claudia, primary, Brancaccio, Giuseppina, additional, Brazzale, Alessandra Rosalba, additional, Lavezzo, Enrico, additional, Onelia, Francesco, additional, Franchin, Elisa, additional, Manuto, Laura, additional, Bianca, Federico, additional, Cianci, Vito, additional, Cattelan, Annamaria, additional, Toppo, Stefano, additional, and Crisanti, Andrea, additional

Published
2021
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40. SARS-CoV-2 Antibody Dynamics, Within-Household Transmission and the Impact of Contact Tracing from Community-Wide Serological Testing in the Italian Municipality of Vo’

Author

Dorigatti, Ilaria, primary, Lavezzo, Enrico, additional, Manuto, Laura, additional, Ciavarella, Constanze, additional, Pacenti, Monia, additional, Boldrin, Caterina, additional, Cattai, Margherita, additional, Saluzzo, Francesca, additional, Franchin, Elisa, additional, Del Vecchio, Claudia, additional, Caldart, Federico, additional, Castelli, Gioele, additional, Nicoletti, Michele, additional, Nieddu, Eleonora, additional, Salvadoretti, Elisa, additional, Labella, Beatrice, additional, Fava, Ludovico, additional, Guglielmo, Simone, additional, Fascina, Mariateresa, additional, Alvisi, Gualtiero, additional, Vanuzzo, Maria Cristina, additional, Zupo, Tiziano, additional, Calandrin, Reginetta, additional, Lisi, Vittoria, additional, Rossi, Lucia, additional, Castigliuolo, Ignazio, additional, Merigliano, Stefano, additional, Unwin, H. Juliette T., additional, Plebani, Mario, additional, Padoan, Andrea, additional, Brazzale, Alessandra R., additional, Toppo, Stefano, additional, Ferguson, Neil M., additional, Donnelly, Christl, additional, and Crisanti, Andrea, additional

Published
2021
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42. Diagnosis and Tracking of SARS-CoV-2 Infection By T-Cell Receptor Sequencing

Author

Gittelman, Rachel M., primary, Lavezzo, Enrico, additional, Snyder, Thomas M., additional, Zahid, H. Jabran, additional, Elyanow, Rebecca, additional, Dalai, Sudeb, additional, Kirsch, Ilan, additional, Baldo, Lance, additional, Manuto, Laura, additional, Franchin, Elisa, additional, Vecchio, Claudia Del, additional, Pacenti, Monia, additional, Boldrin, Caterina, additional, Cattai, Margherita, additional, Saluzzo, Francesca, additional, Padoan, Andrea, additional, Plebani, Mario, additional, Simeoni, Fabio, additional, Bordini, Jessica, additional, Lorè, Nicola I., additional, Lazarevic, Dejan, additional, Cirillo, Daniela M., additional, Ghia, Paolo, additional, Toppo, Stefano, additional, Carlson, Jonathan M., additional, Robins, Harlan S., additional, Tonon, Giovanni, additional, and Crisanti, Andrea, additional

Published
2020
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44. MOESM1 of The CAFA challenge reports improved protein function prediction and new functional annotations for hundreds of genes through experimental screens

Author

Naihui Zhou, Yuxiang Jiang, Bergquist, Timothy, Lee, Alexandra, Balint Kacsoh, Crocker, Alex, Lewis, Kimberley, Georghiou, George, Nguyen, Huy, Md Nafiz Hamid, Davis, Larry, Tunca Dogan, Atalay, Volkan, Rifaioglu, Ahmet, Dalkıran, Alperen, Rengul Cetin Atalay, Chengxin Zhang, Hurto, Rebecca, Freddolino, Peter, Zhang, Yang, Prajwal Bhat, Supek, Fran, Fernández, José, Gemovic, Branislava, Perovic, Vladimir, Davidović, Radoslav, Sumonja, Neven, Veljkovic, Nevena, Ehsaneddin Asgari, Mofrad, Mohammad, Profiti, Giuseppe, Castrense Savojardo, Martelli, Pier Luigi, Casadio, Rita, Boecker, Florian, Schoof, Heiko, Indika Kahanda, Thurlby, Natalie, McHardy, Alice, Renaux, Alexandre, Saidi, Rabie, Gough, Julian, Freitas, Alex, Antczak, Magdalena, Fabris, Fabio, Wass, Mark, Hou, Jie, Jianlin Cheng, Wang, Zheng, Romero, Alfonso, Paccanaro, Alberto, Haixuan Yang, Goldberg, Tatyana, Chenguang Zhao, Holm, Liisa, Törönen, Petri, Medlar, Alan, Zosa, Elaine, Borukhov, Itamar, Novikov, Ilya, Wilkins, Angela, Lichtarge, Olivier, Po-Han Chi, Tseng, Wei-Cheng, Linial, Michal, Rose, Peter, Dessimoz, Christophe, Vidulin, Vedrana, Saso Dzeroski, Sillitoe, Ian, Sayoni Das, Lees, Jonathan Gill, Jones, David, Wan, Cen, Cozzetto, Domenico, Fa, Rui, Torres, Mateo, Vesztrocy, Alex Warwick, Rodriguez, Jose Manuel, Tress, Michael, Frasca, Marco, Notaro, Marco, Grossi, Giuliano, Petrini, Alessandro, Re, Matteo, Valentini, Giorgio, Mesiti, Marco, Roche, Daniel, Reeb, Jonas, Ritchie, David, Sabeur Aridhi, Alborzi, Seyed Ziaeddin, Marie-Dominique Devignes, Koo, Da Chen Emily, Bonneau, Richard, Gligorijević, Vladimir, Meet Barot, Fang, Hai, Toppo, Stefano, Lavezzo, Enrico, Falda, Marco, Berselli, Michele, Tosatto, Silvio, Carraro, Marco, Piovesan, Damiano, Hafeez Ur Rehman, Qizhong Mao, Shanshan Zhang, Vucetic, Slobodan, Black, Gage, Jo, Dane, Suh, Erica, Dayton, Jonathan, Larsen, Dallas, Omdahl, Ashton, McGuffin, Liam, Brackenridge, Danielle, Babbitt, Patricia, Yunes, Jeffrey, Fontana, Paolo, Zhang, Feng, Shanfeng Zhu, Ronghui You, Zihan Zhang, Suyang Dai, Shuwei Yao, Weidong Tian, Renzhi Cao, Chandler, Caleb, Amezola, Miguel, Johnson, Devon, Chang, Jia-Ming, Wen-Hung Liao, Liu, Yi-Wei, Pascarelli, Stefano, Yotam Frank, Hoehndorf, Robert, Kulmanov, Maxat, Boudellioua, Imane, Politano, Gianfranco, Carlo, Stefano Di, Benso, Alfredo, Hakala, Kai, Ginter, Filip, Mehryary, Farrokh, Suwisa Kaewphan, Björne, Jari, Moen, Hans, Tolvanen, Martti, Salakoski, Tapio, Kihara, Daisuke, Aashish Jain, Šmuc, Tomislav, Altenhoff, Adrian, Ben-Hur, Asa, Rost, Burkhard, Brenner, Steven, Orengo, Christine, Jeffery, Constance, Bosco, Giovanni, Hogan, Deborah, Martin, Maria, O’Donovan, Claire, Mooney, Sean, Greene, Casey, Radivojac, Predrag, and Friedberg, Iddo

Subjects
Pharmacology, FOS: Biological sciences, Data_FILES, Genetics, Biochemistry, Molecular Biology, 69999 Biological Sciences not elsewhere classified, Developmental Biology
Abstract

Additional file 1 Additional figures and tables referenced in the article.

Published
2019
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46. KPC-mediated resistance in Klebsiella pneumoniae in two hospitals in Padua, Italy, June 2009-December 2011: massive spreading of a KPC-3-encoding plasmid and involvement of non-intensive care units

Author

Richter Sara N, Frasson Ilaria, Franchin Elisa, Bergo Cristina, Lavezzo Enrico, Barzon Luisa, Cavallaro Antonietta, and Palù Giorgio

Subjects
KPC, Carbapenemase, Klebsiella pneumoniae, Plasmid-mediated antimicrobial resistance, Gram-negative, Nosocomial infections, Diseases of the digestive system. Gastroenterology, RC799-869
Abstract

Abstract Background Klebsiella pneumoniae carbapenemases (KPCs) producing bacteria have emerged as a cause of multidrug-resistant nosocomial infections worldwide. KPCs are plasmid-encoded enzymes capable of hydrolysing a broad spectrum of beta-lactams, including carbapenems and monobactams, therefore worryingly limiting antimicrobial treatment options. Analysis of circulating bacterial strains and KPC alleles may help understanding the route of KPC dissemination and therefore help containing the infection. Methods KPC-producing Klebsiella pneumoniae dissemination in two 1580- and 300- bed hospitals in Padua, Italy, from initial outbreak in 2009 to late 2011 was analysed. Molecular and clinical epidemiology, including bacterial strains, KPC-encoding plasmid sequences and associated resistance genes, involved hospital wards and relocation of patients were described. Routine antimicrobial susceptibility testing and MIC of carbapenems on clinical isolates were performed. Detection of resistance genes was obtained by PCR and sequencing. MLST, PFGE and ERIC were used for molecular genotyping. Plasmid analysis was obtained by digestion with restriction enzymes and deep sequencing. Results KPC-positive clinical samples were isolated from nearly 200 patients. In the initial outbreak intensive care units were almost exclusively involved, while medical, surgical and long-term wards were successively massively concerned. Analysis of KPC alleles, plasmids and bacterial sequence types (STs) indicated that during the initial outbreak KPC-3 in ST258 and KPC-2 in ST147 were each confined in one of the two surveilled hospitals. While KPC-2 dissemination was effectively contained, KPC-3 in ST258 cross-spreading was observed. The simultaneous presence of two carbapenemases, VIM-1 and KPC-2, in the same isolate was also observed in three patients. Total sequencing of plasmid content of two KPC-3 strains showed novel association of resistance plasmids. Conclusions The acquired molecular epidemiology demonstrated that 1) both acquisitions from outward sources and patient relocation within the hospitals were responsible for the observed spreading; 2) KPC-3-encoding Klebsiella pneumoniae ST258 prevailed over other strains. In addition, the described massive transfer of KPC-mediated resistance to non-intensive care units may anticipate spreading of resistance to the non-hospitalized population. Therefore, genotypic analysis alongside phenotypic identification of carbapenemase producers, also at the carriage state, is advisable to prevent and contain further carbapenemase resistance dissemination.

Published
2012
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