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Book ; Online: The Pangenome

Tettelin, Hervé / Medini, Duccio

Diversity, Dynamics and Evolution of Genomes

2020

Author's details	edited by Hervé Tettelin, Duccio Medini
Keywords	Microbial genetics ; Microbial genomics ; Evolutionary biology ; Biomathematics ; Microbial ecology ; Human genetics ; Genetics
Subject code	579.135
Language	English
Size	1 Online-Ressource (XIV, 309 p. 43 illus., 41 illus. in color)
Edition	1st ed. 2020
Publisher	Springer International Publishing ; Imprint: Springer
Publishing place	Cham
Document type	Book ; Online
HBZ-ID	HT020443980
ISBN	978-3-030-38281-0 ; 9783030382803 ; 9783030382827 ; 9783030382834 ; 3-030-38281-8 ; 303038280X ; 3030382826 ; 3030382834
DOI	10.1007/978-3-030-38281-0
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Book ; Online: The Pangenome

Tettelin, Hervé / Medini, Duccio

2020

Abstract: This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of ...

Abstract	This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of the earliest examples of big data in biology that opened biology to the unbounded. The study of genetic variation observed within a species challenges existing views and has profound consequences for our understanding of the fundamental mechanisms underpinning bacterial biology and evolution. The underlying rationale extends well beyond the initial prokaryotic focus to all kingdoms of life and evolves into similar concepts for metagenomes, phenomes and epigenomes. The book's respective chapters address a range of topics, from the serendipitous emergence of the pan-genome concept and its impacts on the fields of microbiology, vaccinology and antimicrobial resistance, to the study of microbial communities, bioinformatic applications and mathematical models that tie in with complex systems and economic theory. Given its scope, the book will appeal to a broad readership interested in population dynamics, evolutionary biology and genomics
Keywords	Biology (General) ; Mathematics ; Ecology ; Medicine (General)
Size	1 electronic resource (307 pages)
Publisher	Springer Nature
Document type	Book ; Online
Note	English ; Open Access
HBZ-ID	HT020481425
ISBN	9783030382810 ; 3030382818
DOI	10.1007/978-3-030-38281-0
Database	ZB MED Catalogue: Medicine, Health, Nutrition, Environment, Agriculture

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Article ; Online: Deep-learning image analysis for high-throughput screening of opsono-phagocytosis-promoting monoclonal antibodies against Neisseria gonorrhoeae.

Vacca, Fabiola / Cardamone, Dario / Andreano, Emanuele / Medini, Duccio / Rappuoli, Rino / Sala, Claudia

Scientific reports

2024 Volume 14, Issue 1, Page(s) 4807

Abstract: Antimicrobial resistance (AMR) is nowadays a global health concern as bacterial pathogens are increasingly developing resistance to antibiotics. Monoclonal antibodies (mAbs) represent a powerful tool for addressing AMR thanks to their high specificity ... ...

Abstract	Antimicrobial resistance (AMR) is nowadays a global health concern as bacterial pathogens are increasingly developing resistance to antibiotics. Monoclonal antibodies (mAbs) represent a powerful tool for addressing AMR thanks to their high specificity for pathogenic bacteria which allows sparing the microbiota, kill bacteria through complement deposition, enhance phagocytosis or inhibit bacterial adhesion to epithelial cells. Here we describe a visual opsono-phagocytosis assay which relies on confocal microscopy to measure the impact of mAbs on phagocytosis of the bacterium Neisseria gonorrhoeae by macrophages. With respect to traditional CFU-based assays, generated images can be automatically analysed by convolutional neural networks. Our results demonstrate that confocal microscopy and deep learning-based analysis allow screening for phagocytosis-promoting mAbs against N. gonorrhoeae, even when mAbs are not purified and are expressed at low concentration. Ultimately, the flexibility of the staining protocol and of the deep-learning approach make the assay suitable for other bacterial species and cell lines where mAb activity needs to be investigated.
MeSH term(s)	Humans ; Neisseria gonorrhoeae ; Antibodies, Monoclonal ; High-Throughput Screening Assays ; Deep Learning ; Anti-Bacterial Agents/pharmacology ; Phagocytosis ; Gonorrhea
Chemical Substances	Antibodies, Monoclonal ; Anti-Bacterial Agents
Language	English
Publishing date	2024-02-27
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-024-55606-4
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Book ; Online: The Pangenome

Tettelin, Hervé / Medini, Duccio

2020

Abstract	This open access book offers the first comprehensive account of the pan-genome concept and its manifold implications. The realization that the genetic repertoire of a biological species always encompasses more than the genome of each individual is one of the earliest examples of big data in biology that opened biology to the unbounded. The study of genetic variation observed within a species challenges existing views and has profound consequences for our understanding of the fundamental mechanisms underpinning bacterial biology and evolution. The underlying rationale extends well beyond the initial prokaryotic focus to all kingdoms of life and evolves into similar concepts for metagenomes, phenomes and epigenomes. The book’s respective chapters address a range of topics, from the serendipitous emergence of the pan-genome concept and its impacts on the fields of microbiology, vaccinology and antimicrobial resistance, to the study of microbial communities, bioinformatic applications and mathematical models that tie in with complex systems and economic theory. Given its scope, the book will appeal to a broad readership interested in population dynamics, evolutionary biology and genomics.
Keywords	Microbial Genetics and Genomics ; Evolutionary Biology ; Genetics and Population Dynamics ; Microbial Ecology ; Human Genetics ; Genetics and Genomics ; Comparative genomics ; Metagenomics ; Microbial Population Analysis ; Pangenome Profile ; Supra-Genome Analysis ; Adaptive Evolution ; Computational Tools ; Bioinformatic Genomics ; Core Dispensable Genome ; Selection ; Recombination ; Composition ; Acquired Resistance ; Bacterial Species Concept ; Genomic Diversity ; Bacterial Ecology ; Microevolution ; Open Access ; Pan-metagenomics ; Pan-microbiomics ; Pan-epigenome ; Gene Transfer ; Pan-phenomes ; Microbiology (non-medical) ; Genetics (non-medical) ; Evolution ; Applied mathematics ; Ecological science ; the Biosphere ; Medical genetics
Language	English
Publisher	Springer Nature
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Comparison of Open-Source Reverse Vaccinology Programs for Bacterial Vaccine Antigen Discovery.

Dalsass, Mattia / Brozzi, Alessandro / Medini, Duccio / Rappuoli, Rino

Frontiers in immunology

2019 Volume 10, Page(s) 113

Abstract: Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational analyses. Since its first application in Group ... ...

Abstract	Reverse Vaccinology (RV) is a widely used approach to identify potential vaccine candidates (PVCs) by screening the proteome of a pathogen through computational analyses. Since its first application in Group B
MeSH term(s)	Animals ; Antigens, Bacterial/immunology ; Antigens, Bacterial/isolation & purification ; Bacterial Infections/immunology ; Bacterial Vaccines/immunology ; Computational Biology ; Datasets as Topic ; High-Throughput Screening Assays ; Humans ; Machine Learning ; Proteomics ; Software ; Vaccinology/trends
Chemical Substances	Antigens, Bacterial ; Bacterial Vaccines
Language	English
Publishing date	2019-02-14
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2606827-8
ISSN	1664-3224 ; 1664-3224
ISSN (online)	1664-3224
ISSN	1664-3224
DOI	10.3389/fimmu.2019.00113
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A re-assessment of 4CMenB vaccine effectiveness against serogroup B invasive meningococcal disease in England based on an incidence model.

Argante, Lorenzo / Abbing-Karahagopian, Victoria / Vadivelu, Kumaran / Rappuoli, Rino / Medini, Duccio

BMC infectious diseases

2021 Volume 21, Issue 1, Page(s) 1244

Abstract: Background: The four-component serogroup B meningococcal 4CMenB vaccine (Bexsero, GSK) has been routinely given to all infants in the United Kingdom at 2, 4 and 12 months of age since September 2015. After 3 years, Public Health England (PHE) reported a ...

Abstract	Background: The four-component serogroup B meningococcal 4CMenB vaccine (Bexsero, GSK) has been routinely given to all infants in the United Kingdom at 2, 4 and 12 months of age since September 2015. After 3 years, Public Health England (PHE) reported a 75% [95% confidence interval 64%; 81%] reduction in the incidence of serogroup B invasive meningococcal disease (IMD) in age groups eligible to be fully vaccinated. In contrast, vaccine effectiveness (VE) evaluated in the same immunization program applying the screening method was not statistically significant. We re-analyzed the data using an incidence model. Methods: Aggregate data-stratified by age, year and doses received-were provided by PHE: serogroup B IMD case counts for the entire population of England (years 2011-2018) and 4CMenB vaccine uptake in infants. We combined uptake with national population estimates to obtain counts of vaccinated and unvaccinated person-time by age and time. We re-estimated VE comparing incidence rates in vaccinated and non-vaccinated subjects using a Bayesian Poisson model for case counts with person-time data as an offset. The model was adjusted for age, time and number of doses received. Results: The incidence model showed that cases decreased until 2013-2014, followed by an increasing trend that continued in the non-vaccinated population during the immunization program. VE in fully vaccinated subjects (three doses) was 80.1% [95% Bayesian credible interval (BCI): 70.3%; 86.7%]. After a single dose, VE was 33.5% [12.4%; 49.7%] Conclusions: Our estimates of VE had higher precision than previous estimates based on the screening method, which were statistically not significant, and in line with the 75% incidence reduction previously reported by PHE. When disease incidence is low and vaccine uptake is high, the screening method applied to cases exclusively from the population eligible for vaccination may not be precise enough and may produce misleading point-estimates. Precise and accurate VE estimates are fundamental to inform public health decision making. VE assessment can be enhanced using models that leverage data on subjects not eligible for vaccination.
MeSH term(s)	Bayes Theorem ; England/epidemiology ; Humans ; Incidence ; Infant ; Meningococcal Infections/epidemiology ; Meningococcal Infections/prevention & control ; Meningococcal Vaccines ; Neisseria meningitidis, Serogroup B ; Serogroup ; Vaccine Efficacy
Chemical Substances	4CMenB vaccine ; Meningococcal Vaccines
Language	English
Publishing date	2021-12-11
Publishing country	England
Document type	Journal Article
ZDB-ID	2041550-3
ISSN	1471-2334 ; 1471-2334
ISSN (online)	1471-2334
ISSN	1471-2334
DOI	10.1186/s12879-021-06906-x
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Evaluating the Impact of Meningococcal Vaccines With Synthetic Controls.

Prunas, Ottavia / Weinberger, Daniel M / Medini, Duccio / Tizzoni, Michele / Argante, Lorenzo

American journal of epidemiology

2021 Volume 191, Issue 4, Page(s) 724–734

Abstract: Invasive meningococcal disease (IMD) has a low and unpredictable incidence, presenting challenges for real-world evaluations of meningococcal vaccines. Traditionally, meningococcal vaccine impact is evaluated by predicting counterfactuals from pre- ... ...

Abstract	Invasive meningococcal disease (IMD) has a low and unpredictable incidence, presenting challenges for real-world evaluations of meningococcal vaccines. Traditionally, meningococcal vaccine impact is evaluated by predicting counterfactuals from pre-immunization IMD incidences, possibly controlling for IMD in unvaccinated age groups, but the selection of controls can influence results. We retrospectively applied a synthetic control (SC) method, previously used for pneumococcal disease, to data from 2 programs for immunization of infants against serogroups B and C IMD in England and Brazil. Time series of infectious/noninfectious diseases in infants and IMD cases in older unvaccinated age groups were used as candidate controls, automatically combined in a SC through Bayesian variable selection. SC closely predicted IMD in absence of vaccination, adjusting for nontrivial changes in IMD incidence. Vaccine impact estimates were in line with previous assessments. IMD cases in unvaccinated age groups were the most frequent SC-selected controls. Similar results were obtained when excluding IMD from control sets and using other diseases only, particularly respiratory diseases and measles. Using non-IMD controls may be important where there are herd immunity effects. SC is a robust and flexible method that addresses uncertainty introduced when equally plausible controls exhibit different post-immunization behaviors, allowing objective comparisons of IMD programs between countries.
MeSH term(s)	Aged ; Bayes Theorem ; Humans ; Incidence ; Infant ; Meningococcal Infections/epidemiology ; Meningococcal Infections/prevention & control ; Meningococcal Vaccines ; Retrospective Studies ; Vaccination ; Vaccines, Conjugate
Chemical Substances	Meningococcal Vaccines ; Vaccines, Conjugate
Language	English
Publishing date	2021-11-09
Publishing country	United States
Document type	Journal Article
ZDB-ID	2937-3
ISSN	1476-6256 ; 0002-9262
ISSN (online)	1476-6256
ISSN	0002-9262
DOI	10.1093/aje/kwab266
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Interplay Between Virulence and Variability Factors as a Potential Driver of Invasive Meningococcal Disease

Siena, Emilio / Bodini, Margherita / Medini, Duccio

Computational and Structural Biotechnology Journal. 2018, v. 16

2018

Abstract: Neisseria meningitidis (Nm) is frequently found in the upper respiratory tract of the human population. Despite its prevalence as a commensal organism, Nm can occasionally invade the pharyngeal mucosal epithelium causing septicemia and life-threatening ... ...

Abstract	Neisseria meningitidis (Nm) is frequently found in the upper respiratory tract of the human population. Despite its prevalence as a commensal organism, Nm can occasionally invade the pharyngeal mucosal epithelium causing septicemia and life-threatening disease. A number of studies have tried to identify factors that are responsible for the onset of a virulent phenotype. Despite this however, we still miss clear causative elements. Several factors have been identified to be associated to an increased susceptibility to meningococcal disease in humans. None of them, however, could unambiguously discriminate healthy carrier from infected individuals. Similarly, comparative studies of virulent and apathogenic strains failed to identify virulence factors that could explain the emergence of the pathogenic phenotype. In line with this, a recent study of within host evolution found that Nm accumulates genomic changes during the asymptomatic carriage phase and that these are likely to contribute to the shift to a pathogenic phenotype. These results suggest that the presence of virulence factors in the meningococcal genome is not a sufficient condition for developing virulent traits, but is rather the ability to promote phenotypic variation, through the stochastic assortment of the repertoire of such factors, which could explain the occasional and unpredictable onset of IMD. Here, we present a series of argumentations supporting the hypothesis that invasive meningococcal disease comes as a result of the coexistence of bacterial virulence and variability factors in a plot that can be further complicated by additional latent factors, like host pre-existing immune status and genetic predisposition.
Keywords	Neisseria meningitidis ; avirulent strains ; epithelium ; evolution ; genome ; genomics ; humans ; pharynx ; phenotype ; phenotypic variation ; respiratory system ; septicemia ; virulence
Language	English
Size	p. 61-69.
Publishing place	Elsevier B.V.
Document type	Article
ISSN	2001-0370
DOI	10.1016/j.csbj.2018.02.002
Database	NAL-Catalogue (AGRICOLA)

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Article: Interplay Between Virulence and Variability Factors as a Potential Driver of Invasive Meningococcal Disease.

Siena, Emilio / Bodini, Margherita / Medini, Duccio

Computational and structural biotechnology journal

2018 Volume 16, Page(s) 61–69

Language	English
Publishing date	2018-02-15
Publishing country	Netherlands
Document type	Journal Article ; Review
ISSN	2001-0370
ISSN	2001-0370
DOI	10.1016/j.csbj.2018.02.002
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Genetic Features of a Representative Panel of 110 Meningococcal B Isolates to Assess the Efficacy of Meningococcal B Vaccines.

Muzzi, Alessandro / Bodini, Margherita / Topaz, Nadav / Masignani, Vega / Vadivelu, Kumaran / Marjuki, Henju / Wang, Xin / Serino, Laura / Medini, Duccio

mSphere

2022 Volume 7, Issue 5, Page(s) e0038522

Abstract: Predictions of vaccine efficacy against Neisseria meningitidis serogroup B (NmB) disease are hindered by antigenic variability, limiting the representativeness of individual NmB isolates. A qualitative human serum bactericidal assay using endogenous ... ...

Abstract	Predictions of vaccine efficacy against Neisseria meningitidis serogroup B (NmB) disease are hindered by antigenic variability, limiting the representativeness of individual NmB isolates. A qualitative human serum bactericidal assay using endogenous complements of individual subjects (enc-hSBA) enables large panels of NmB isolates to be tested. A 110-isolate panel was randomly selected from 442 invasive NmB isolates from United States cases reported to the Centers for Disease Control (CDC) from 2000 to 2008. Typing analyses confirmed the 110-isolate panel is representative of the 442 isolates. The genetic features of the 110-isolate panel were compared against over 4,200 invasive NmB isolates collected from 2000 to 2018 in the United States, Australia, Canada, and nine European countries. Clonal complexes in the 110-isolate panel are also present in each geographical region; cumulative percentages show that these account for around 81% of the clonal complexes found in NmB isolates in other panels. For the antigens (fHbp, NHBA, PorA1.4, NadA) included in the currently licensed meningococcal serogroup B (MenB) vaccines, specifically considering the presence of at least one antigen with a matched genotype, the 110-isolate panel represents approximately 89% of the NmB isolates circulating worldwide, ranging from 87% for the European isolates to 95% and 97% for NmB isolates in the United States and Australia, respectively. The 110-isolate panel includes the most prevalent clonal complexes and genetic variants of MenB vaccine antigens found in a multinational collection of invasive NmB isolates. This panel is useful for assessing the efficacy of MenB vaccines in clinical trials worldwide.
MeSH term(s)	Humans ; United States ; Antigens, Bacterial/genetics ; Meningococcal Vaccines ; Neisseria meningitidis, Serogroup B ; Meningococcal Infections/prevention & control ; Genotype
Chemical Substances	Antigens, Bacterial ; Meningococcal Vaccines
Language	English
Publishing date	2022-09-21
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ISSN	2379-5042
ISSN (online)	2379-5042
DOI	10.1128/msphere.00385-22
Database	MEDical Literature Analysis and Retrieval System OnLINE

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