Publications

@article{Wegner2024,

title = {How much should we sequence? An analysis of the Swiss SARS-CoV-2 surveillance effort},

author = {Fanny Wegner and Blanca Cabrera-Gil and Araud Tanguy and Christiane Beckmann and Niko Beerenwinkel and Claire Bertelli and Matteo Carrara and Lorenzo Cerutti and Chaoran Chen and Samuel Cordey and Alexis Dumoulin and Louis du Plessis and Marc Friedli and Yannick Gerth and Gilbert Greub and Adrian Härri and Hans Hirsch and Cedric Howald and Michael Huber and Alexander Imhof and Laurent Kaiser and Verena Kufner and Stephen L. Leib and Karoline Leuzinger and Etleva Lleshi and Gladys Martinetti and Mirjam Mäusezahl and Milo Moraz and Richard Neher and Oliver Nolte and Alban Ramette and Maurice Redondo and Lorenz Risch and Lionel Rohner and Tim Roloff and Pascal Schläepfer and Katrin Schneider and Franziska Singer and Valeria Spina and Tanja Stadler and Erik Studer and Ivan Topolsky and Alexandra Trkola and Daniel Walther and Nadia Wohlwend and Cinzia Zehnder and Aitana Neves and Adrian Egli and },

editor = {Sophia B. Georghiou},

doi = {10.1128/spectrum.03628-23},

issn = {2165-0497},

year  = {2024},

date = {2024-05-02},

journal = {Microbiol Spectr},

volume = {12},

number = {5},

publisher = {American Society for Microbiology},

abstract = {ABSTRACT

          

            

            During the SARS-CoV-2 pandemic, many countries directed substantial resources toward genomic surveillance to detect and track viral variants. There is a debate over how much sequencing effort is necessary in national surveillance programs for SARS-CoV-2 and future pandemic threats. We aimed to investigate the effect of reduced sequencing on surveillance outcomes in a large genomic data set from Switzerland, comprising more than 143k sequences. We employed a uniform downsampling strategy using 100 iterations each to investigate the effects of fewer available sequences on the surveillance outcomes: (i) first detection of variants of concern (VOCs), (ii) speed of introduction of VOCs, (iii) diversity of lineages, (iv) first cluster detection of VOCs, (v) density of active clusters, and (vi) geographic spread of clusters. The impact of downsampling on VOC detection is disparate for the three VOC lineages, but many outcomes including introduction and cluster detection could be recapitulated even with only 35% of the original sequencing effort. The effect on the observed speed of introduction and first detection of clusters was more sensitive to reduced sequencing effort for some VOCs, in particular Omicron and Delta, respectively. A genomic surveillance program needs a balance between societal benefits and costs. While the overall national dynamics of the pandemic could be recapitulated by a reduced sequencing effort, the effect is strongly lineage-dependent—something that is unknown at the time of sequencing—and comes at the cost of accuracy, in particular for tracking the emergence of potential VOCs.

            

              IMPORTANCE

              Switzerland had one of the most comprehensive genomic surveillance systems during the COVID-19 pandemic. Such programs need to strike a balance between societal benefits and program costs. Our study aims to answer the question: How would surveillance outcomes have changed had we sequenced less? We find that some outcomes but also certain viral lineages are more affected than others by sequencing less. However, sequencing to around a third of the original effort still captured many important outcomes for the variants of concern such as their first detection but affected more strongly other measures like the detection of first transmission clusters for some lineages. Our work highlights the importance of setting predefined targets for a national genomic surveillance program based on which sequencing effort should be determined. Additionally, the use of a centralized surveillance platform facilitates aggregating data on a national level for rapid public health responses as well as post-analyses.

            

          },

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pubstate = {published},

tppubtype = {article}

}

@article{Neves2023,

title = {A survey into the contribution of regional/national pathogen data platforms and on the resources needed to develop and maintain them},

author = {Aitana Neves and Nils P Willassen and Erik Hjerde and Isabel Cuesta and Corinne S Martin and Heleri Inno and Diana Pilvar and Kim Ng and David Salgado and Jacques van Helden and Wei Gu and Marina Popleteeva and Joaquin Dopazo and Timotej Šuri and Jan Pačes and Cezary Mazurek and Krzysztof Kurowski and Natalia Koralewska and Gunter Maier and },

doi = {10.12688/f1000research.142165.1},

issn = {2046-1402},

year  = {2023},

date = {2023-12-14},

journal = {F1000Res},

volume = {12},

publisher = {F1000 Research Ltd},

abstract = {Background Regional/national SARS-CoV-2 genomic data platforms (DP) have played a key role during the Covid-19 pandemic to centralize data, curate, process and re-share them in a consistent form and pseudonymized/anonymized to international repositories. In Europe, several countries were able to establish such infrastructures rapidly and put them in production over the course of 2021, some earlier. Methods This survey aimed to estimate the effort that was needed to establish and run these DPs during the sequencing peak of the pandemic in 2021, including activities from data curation to data brokering, and what it would take to expand these DPs to other pathogens and antimicrobial resistance from 2023 onwards. Results Overall, a median of 10 person-months (PM) were used by each DP over 2021 and a median of 18 PM (per year) would be needed to expand activities from 2023 onwards. This survey shows that short-term funding remains commonplace and a struggle for the majority of DPs. Key supporters and arguments (e.g. centered around efficiency and cost-savings) for public health authorities and research funding bodies have also been identified to help individual data platforms in strengthening their funding proposals. Conclusions Ultimately, we propose that DPs get connected into a supra-national entity to build a stronger case and get access to major infrastructure funding grants at the European and global levels.},

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}

@article{Neves2023b,

title = {FAIR+E pathogen data for surveillance and research: lessons from COVID-19},

author = {Aitana Neves and Isabel Cuesta and Erik Hjerde and Terje Klemetsen and David Salgado and Jacques van Helden and Nadim Rahman and Nazeefa Fatima and Nestoras Karathanasis and Pawel Zmora and Wolmar Nyberg Åkerström and Sushma Nagaraja Grellscheid and Zahra Waheed and Niklas Blomberg},

doi = {10.3389/fpubh.2023.1289945},

issn = {2296-2565},

year  = {2023},

date = {2023-11-21},

journal = {Front. Public Health},

volume = {11},

publisher = {Frontiers Media SA},

abstract = {The COVID-19 pandemic has exemplified the importance of interoperable and equitable data sharing for global surveillance and to support research. While many challenges could be overcome, at least in some countries, many hurdles within the organizational, scientific, technical and cultural realms still remain to be tackled to be prepared for future threats. We propose to (i) continue supporting global efforts that have proven to be efficient and trustworthy toward addressing challenges in pathogen molecular data sharing; (ii) establish a distributed network of Pathogen Data Platforms to (a) ensure high quality data, metadata standardization and data analysis, (b) perform data brokering on behalf of data providers both for research and surveillance, (c) foster capacity building and continuous improvements, also for pandemic preparedness; (iii) establish an International One Health Pathogens Portal, connecting pathogen data isolated from various sources (human, animal, food, environment), in a truly One Health approach and following FAIR principles. To address these challenging endeavors, we have started an ELIXIR Focus Group where we invite all interested experts to join in a concerted, expert-driven effort toward sustaining and ensuring high-quality data for global surveillance and research.},

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@article{pmid37171846,

title = {The Swiss Pathogen Surveillance Platform - towards a nation-wide One Health data exchange platform for bacterial, viral and fungal genomics and associated metadata},

author = {Aitana Neves and Daniel Walther and Trinidad Martin-Campos and Valerie Barbie and Claire Bertelli and Dominique Blanc and Gérard Bouchet and Frédéric Erard and Gilbert Greub and Hans H Hirsch and Michael Huber and Laurent Kaiser and Stephen L Leib and Karoline Leuzinger and Vladimir Lazarevic and Mirjam Mäusezahl and Jorge Molina and Richard A Neher and Vincent Perreten and Alban Ramette and Tim Roloff and Jacques Schrenzel and Helena M B Seth-Smith and Roger Stephan and Dillenn Terumalai and Fanny Wegner and Adrian Egli},

doi = {10.1099/mgen.0.001001},

issn = {2057-5858},

year  = {2023},

date = {2023-05-01},

journal = {Microb Genom},

volume = {9},

number = {5},

abstract = {The Swiss Pathogen Surveillance Platform (SPSP) is a shared secure surveillance platform between human and veterinary medicine, to also include environmental and foodborne isolates. It enables rapid and detailed transmission monitoring and outbreak surveillance of pathogens using whole genome sequencing data and associated metadata. It features controlled data access, complex dynamic queries, dedicated dashboards and automated data sharing with international repositories, providing actionable results for public health and the vision to improve societal well-being and health.},

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pubstate = {published},

tppubtype = {article}

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@article{Dylus2020,

title = {NGS-Based S. aureus Typing and Outbreak Analysis in Clinical Microbiology Laboratories: Lessons Learned From a Swiss-Wide Proficiency Test},

author = {David Dylus and Trestan Pillonel and Onya Opota and Daniel Wüthrich and Helena M. B. Seth-Smith and Adrian Egli and Stefano Leo and Vladimir Lazarevic and Jacques Schrenzel and Sacha Laurent and Claire Bertelli and Dominique S. Blanc and Stefan Neuenschwander and Alban Ramette and Laurent Falquet and Frank Imkamp and Peter M. Keller and Andre Kahles and Simone Oberhaensli and Valérie Barbié and Christophe Dessimoz and Gilbert Greub and Aitana Lebrand},

doi = {10.3389/fmicb.2020.591093},

issn = {1664-302X},

year  = {2020},

date = {2020-11-24},

journal = {Front. Microbiol.},

volume = {11},

publisher = {Frontiers Media SA},

abstract = {Whole genome sequencing (WGS) enables high resolution typing of bacteria up to the single nucleotide polymorphism (SNP) level. WGS is used in clinical microbiology laboratories for infection control, molecular surveillance and outbreak analyses. Given the large palette of WGS reagents and bioinformatics tools, the Swiss clinical bacteriology community decided to conduct a ring trial (RT) to foster harmonization of NGS-based bacterial typing. The RT aimed at assessing methicillin-susceptible Staphylococcus aureus strain relatedness from WGS and epidemiological data. The RT was designed to disentangle the variability arising from differences in sample preparation, SNP calling and phylogenetic methods. Nine laboratories participated. The resulting phylogenetic tree and cluster identification were highly reproducible across the laboratories. Cluster interpretation was, however, more laboratory dependent, suggesting that an increased sharing of expertise across laboratories would contribute to further harmonization of practices. More detailed bioinformatic analyses unveiled that while similar clusters were found across laboratories, these were actually based on different sets of SNPs, differentially retained after sample preparation and SNP calling procedures. Despite this, the observed number of SNP differences between pairs of strains, an important criterion to determine strain relatedness given epidemiological information, was similar across pipelines for closely related strains when restricting SNP calls to a common core genome defined by S. aureus cgMLST schema. The lessons learned from this pilot study will serve the implementation of larger-scale RT, as a mean to have regular external quality assessments for laboratories performing WGS analyses in a clinical setting.},

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pubstate = {published},

tppubtype = {article}

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@article{Junier2019,

title = {Viral Metagenomics in the Clinical Realm: Lessons Learned from a Swiss-Wide Ring Trial},

author = {Thomas Junier and Michael Huber and Stefan Schmutz and Verena Kufner and Osvaldo Zagordi and Stefan Neuenschwander and Alban Ramette and Jakub Kubacki and Claudia Bachofen and Weihong Qi and Florian Laubscher and Samuel Cordey and Laurent Kaiser and Christian Beuret and Valérie Barbié and Jacques Fellay and Aitana Lebrand},

doi = {10.3390/genes10090655},

issn = {2073-4425},

year  = {2019},

date = {2019-09-00},

journal = {Genes},

volume = {10},

number = {9},

publisher = {MDPI AG},

abstract = {Shotgun metagenomics using next generation sequencing (NGS) is a promising technique to analyze both DNA and RNA microbial material from patient samples. Mostly used in a research setting, it is now increasingly being used in the clinical realm as well, notably to support diagnosis of viral infections, thereby calling for quality control and the implementation of ring trials (RT) to benchmark pipelines and ensure comparable results. The Swiss NGS clinical virology community therefore decided to conduct a RT in 2018, in order to benchmark current metagenomic workflows used at Swiss clinical virology laboratories, and thereby contribute to the definition of common best practices. The RT consisted of two parts (increments), in order to disentangle the variability arising from the experimental compared to the bioinformatics parts of the laboratory pipeline. In addition, the RT was also designed to assess the impact of databases compared to bioinformatics algorithms on the final results, by asking participants to perform the bioinformatics analysis with a common database, in addition to using their own in-house database. Five laboratories participated in the RT (seven pipelines were tested). We observed that the algorithms had a stronger impact on the overall performance than the choice of the reference database. Our results also suggest that differences in sample preparation can lead to significant differences in the performance, and that laboratories should aim for at least 5–10 Mio reads per sample and use depth of coverage in addition to other interpretation metrics such as the percent of coverage. Performance was generally lower when increasing the number of viruses per sample. The lessons learned from this pilot study will be useful for the development of larger-scale RTs to serve as regular quality control tests for laboratories performing NGS analyses of viruses in a clinical setting.},

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@article{Egli2018,

title = {Improving the quality and workflow of bacterial genome sequencing and analysis: paving the way for a Switzerland-wide molecular epidemiological surveillance platform},

author = {Adrian Egli and Dominique S. Blanc and Gilbert Greub and Peter M. Keller and Vladimir Lazarevic and Aitana Lebrand and Stephen Leib and Richard A. Neher and Vincent Perreten and Alban Ramette and Jacques Schrenzel and Roger Stephan and Karolin Wagner and Daniel Wuethrich and Ioannis Xenarios},

doi = {10.4414/smw.2018.14693},

issn = {1424-3997},

year  = {2018},

date = {2018-12-15},

journal = {Swiss Med Wkly},

publisher = {SMW Supporting Association},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{nokey,

title = {Modern Microbiological Surveillance for Antibiotic Drug Resistance. In Federal Office of Public Health and Federal Food Safety and Veterinary Office.},

author = {Wüthrich D; Blanc D, Greub G; Perreten V; Schrenzel J; Stephan R; Neves A; Xenarios I; Neher R; Egli A. },

year  = {2018},

date = {2018-11-01},

urldate = {2018-11-01},

journal = {Swiss Antibiotic Resistance Report 2018. Usage of Antibiotics and Occurrence of Antibiotic Resistance in Bacteria from Humans and Animals in Switzerland},

keywords = {},

pubstate = {published},

tppubtype = {article}

}