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Article: CovidPhy: A tool for phylogeographic analysis of SARS-CoV-2 variation

Bello, Xabier / Pardo-Seco, Jacobo / Gómez-Carballa, Alberto / Weissensteiner, Hansi / Martinón-Torres, Federico / Salas, Antonio

Environmental research. 2022 Mar., v. 204

2022

Abstract: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 genomes have been sequenced massively and worldwide and are now available in different public ... ...

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 genomes have been sequenced massively and worldwide and are now available in different public genome repositories. There is much interest in generating bioinformatic tools capable to analyze and interpret SARS-CoV-2 variation. We have designed CovidPhy (http://covidphy.eu), a web interface that can process SARS-CoV-2 genome sequences in plain fasta text format or provided through identity codes from the Global Initiative on Sharing Avian Influenza Data (GISAID) or GenBank. CovidPhy aggregates information available on the large GISAID database (>1.49 M genomes). Sequences are first aligned against the reference sequence and the interface provides different sources of information, including automatic classification of genomes into a pre-computed phylogeny and phylogeographic information, haplogroup/lineage frequencies, and sequencing variation, indicating also if the genome contains known variants of concern (VOC). Additionally, CovidPhy allows searching for variants and haplotypes introduced by the user and includes a list of genomes that are good candidates for being responsible for large outbreaks worldwide, most likely mediated by important superspreading events, indicating their possible geographic epicenters and their relative impact as recorded in the GISAID database.
Keywords	COVID-19 infection ; Severe acute respiratory syndrome coronavirus 2 ; avian influenza ; bioinformatics ; databases ; genome ; haplotypes ; pandemic ; pathogens ; phylogeny ; phylogeography ; research ; user interface
Language	English
Dates of publication	2022-03
Publishing place	Elsevier Inc.
Document type	Article
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2021.111909
Database	NAL-Catalogue (AGRICOLA)

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Article: Pitfalls of barcodes in the study of worldwide SARS-CoV-2 variation and phylodynamics.

Pardo-Seco, Jacobo / Gómez-Carballa, Alberto / Bello, Xabier / Martinón-Torres, Federico / Salas, Antonio

Zoological research

2021 Volume 42, Issue 1, Page(s) 87–93

Abstract: Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks. We show that purely mathematical procedures for site selection should be supervised by known phylogeny ( ... ...

Abstract	Analysis of SARS-CoV-2 genome variation using a minimal number of selected informative sites conforming a genetic barcode presents several drawbacks. We show that purely mathematical procedures for site selection should be supervised by known phylogeny (i) to ensure that solid tree branches are represented instead of mutational hotspots with poor phylogeographic proprieties, and (ii) to avoid phylogenetic redundancy. We propose a procedure that prevents information redundancy in site selection by considering the cumulative informativeness of previously selected sites (as a proxy for phylogenetic-based criteria). This procedure demonstrates that, for short barcodes (e.g., 11 sites), there are thousands of informative site combinations that improve previous proposals. We also show that barcodes based on worldwide databases inevitably prioritize variants located at the basal nodes of the phylogeny, such that most representative genomes in these ancestral nodes are no longer in circulation. Consequently, coronavirus phylodynamics cannot be properly captured by universal genomic barcodes because most SARS-CoV-2 variation is generated in geographically restricted areas by the continuous introduction of domestic variants.
MeSH term(s)	Algorithms ; COVID-19/virology ; DNA Barcoding, Taxonomic ; Genetic Variation ; Genome, Viral ; Humans ; Mutation ; Phylogeny ; Phylogeography ; SARS-CoV-2/classification ; SARS-CoV-2/genetics ; SARS-CoV-2/isolation & purification
Language	English
Publishing date	2021-01-07
Publishing country	China
Document type	Letter
ISSN	2095-8137
ISSN	2095-8137
DOI	10.24272/j.issn.2095-8137.2020.364
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Superspreading in the emergence of COVID-19 variants.

Gómez-Carballa, Alberto / Pardo-Seco, Jacobo / Bello, Xabier / Martinón-Torres, Federico / Salas, Antonio

Trends in genetics : TIG

2021 Volume 37, Issue 12, Page(s) 1069–1080

Abstract: Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is ... ...

Abstract	Superspreading and variants of concern (VOC) of the human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are the main catalyzers of the coronavirus disease 2019 (COVID-19) pandemic. However, measuring their individual impact is challenging. By examining the largest database of SARS-CoV-2 genomes The Global Initiative on Sharing Avian Influenza Data [GISAID; n >1.2 million high-quality (HQ) sequences], we present evidence suggesting that superspreading has had a key role in the epidemiological predominance of VOC. There are clear signatures in the database compatible with large superspreading events (SSEs) coinciding chronologically with the worst epidemiological scenarios triggered by VOC. The data suggest that, without the randomness effect of the genetic drift facilitated by superspreading, new VOC of SARS-CoV-2 would have had more limited chance of success.
MeSH term(s)	Animals ; COVID-19 ; Humans ; Pandemics ; SARS-CoV-2/classification
Language	English
Publishing date	2021-09-08
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	619240-3
ISSN	1362-4555 ; 0168-9525 ; 0168-9479
ISSN (online)	1362-4555
ISSN	0168-9525 ; 0168-9479
DOI	10.1016/j.tig.2021.09.003
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Article ; Online: A Timeframe for SARS-CoV-2 Genomes: A Proof of Concept for Postmortem Interval Estimations.

Pardo-Seco, Jacobo / Bello, Xabier / Gómez-Carballa, Alberto / Martinón-Torres, Federico / Muñoz-Barús, José Ignacio / Salas, Antonio

International journal of molecular sciences

2022 Volume 23, Issue 21

Abstract: Establishing the timeframe when a particular virus was circulating in a population could be useful in several areas of biomedical research, including microbiology and legal medicine. Using simulations, we demonstrate that the circulation timeframe of an ... ...

Abstract	Establishing the timeframe when a particular virus was circulating in a population could be useful in several areas of biomedical research, including microbiology and legal medicine. Using simulations, we demonstrate that the circulation timeframe of an unknown SARS-CoV-2 genome in a population (hereafter, estimated time of a queried genome [QG];
MeSH term(s)	Humans ; SARS-CoV-2/genetics ; Phylogeny ; COVID-19 ; Genome, Viral ; Mutation
Language	English
Publishing date	2022-10-25
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms232112899
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Article ; Online: Mapping genome variation of SARS-CoV-2 worldwide highlights the impact of COVID-19 super-spreaders.

Gómez-Carballa, Alberto / Bello, Xabier / Pardo-Seco, Jacobo / Martinón-Torres, Federico / Salas, Antonio

Genome research

2020 Volume 30, Issue 10, Page(s) 1434–1448

Abstract: The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. ... ...

Abstract	The human pathogen severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the major pandemic of the twenty-first century. We analyzed more than 4700 SARS-CoV-2 genomes and associated metadata retrieved from public repositories. SARS-CoV-2 sequences have a high sequence identity (>99.9%), which drops to >96% when compared to bat coronavirus genome. We built a mutation-annotated reference SARS-CoV-2 phylogeny with two main macro-haplogroups, A and B, both of Asian origin, and more than 160 sub-branches representing virus strains of variable geographical origins worldwide, revealing a rather uniform mutation occurrence along branches that could have implications for diagnostics and the design of future vaccines. Identification of the root of SARS-CoV-2 genomes is not without problems, owing to conflicting interpretations derived from either using the bat coronavirus genomes as an outgroup or relying on the sampling chronology of the SARS-CoV-2 genomes and TMRCA estimates; however, the overall scenario favors haplogroup A as the ancestral node. Phylogenetic analysis indicates a TMRCA for SARS-CoV-2 genomes dating to November 12, 2019, thus matching epidemiological records. Sub-haplogroup A2 most likely originated in Europe from an Asian ancestor and gave rise to subclade A2a, which represents the major non-Asian outbreak, especially in Africa and Europe. Multiple founder effect episodes, most likely associated with super-spreader hosts, might explain COVID-19 pandemic to a large extent.
MeSH term(s)	Animals ; Asia/epidemiology ; Base Sequence/genetics ; Betacoronavirus/genetics ; COVID-19 ; Chiroptera/virology ; Chromosome Mapping ; Coronavirus Infections/epidemiology ; Europe/epidemiology ; Evolution, Molecular ; Genetic Variation/genetics ; Genome, Viral/genetics ; Humans ; Pandemics ; Phylogeny ; Phylogeography ; Pneumonia, Viral/epidemiology ; SARS-CoV-2 ; Sequence Homology, Nucleic Acid
Keywords	covid19
Language	English
Publishing date	2020-09-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	1284872-4
ISSN	1549-5469 ; 1088-9051 ; 1054-9803
ISSN (online)	1549-5469
ISSN	1088-9051 ; 1054-9803
DOI	10.1101/gr.266221.120
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Identification of a Minimal 3-Transcript Signature to Differentiate Viral from Bacterial Infection from Best Genome-Wide Host RNA Biomarkers: A Multi-Cohort Analysis.

Gómez-Carballa, Alberto / Barral-Arca, Ruth / Cebey-López, Miriam / Bello, Xabier / Pardo-Seco, Jacobo / Martinón-Torres, Federico / Salas, Antonio

International journal of molecular sciences

2021 Volume 22, Issue 6

Abstract: The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and ... ...

Abstract	The fight against the spread of antibiotic resistance is one of the most important challenges facing health systems worldwide. Given the limitations of current diagnostic methods, the development of fast and accurate tests for the diagnosis of viral and bacterial infections would improve patient management and treatment, as well as contribute to reducing antibiotic misuse in clinical settings. In this scenario, analysis of host transcriptomics constitutes a promising target to develop new diagnostic tests based on the host-specific response to infections. We carried out a multi-cohort meta-analysis of blood transcriptomic data available in public databases, including 11 different studies and 1209 samples from virus- (
MeSH term(s)	Area Under Curve ; Bacterial Infections/genetics ; Bacterial Infections/microbiology ; Biomarkers ; Cohort Studies ; Computational Biology/methods ; Gene Expression Profiling ; Host-Pathogen Interactions/genetics ; Humans ; Meta-Analysis as Topic ; ROC Curve ; Transcriptome ; Virus Diseases/genetics ; Virus Diseases/virology
Chemical Substances	Biomarkers
Language	English
Publishing date	2021-03-19
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms22063148
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: CovidPhy: A tool for phylogeographic analysis of SARS-CoV-2 variation.

Bello, Xabier / Pardo-Seco, Jacobo / Gómez-Carballa, Alberto / Weissensteiner, Hansi / Martinón-Torres, Federico / Salas, Antonio

Environmental research

2021 Volume 204, Issue Pt A, Page(s) 111909

Abstract	The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the pathogen responsible for the coronavirus disease 2019 (COVID-19) pandemic. SARS-CoV-2 genomes have been sequenced massively and worldwide and are now available in different public genome repositories. There is much interest in generating bioinformatic tools capable to analyze and interpret SARS-CoV-2 variation. We have designed CovidPhy (http://covidphy.eu), a web interface that can process SARS-CoV-2 genome sequences in plain fasta text format or provided through identity codes from the Global Initiative on Sharing Avian Influenza Data (GISAID) or GenBank. CovidPhy aggregates information available on the large GISAID database (>1.49 M genomes). Sequences are first aligned against the reference sequence and the interface provides different sources of information, including automatic classification of genomes into a pre-computed phylogeny and phylogeographic information, haplogroup/lineage frequencies, and sequencing variation, indicating also if the genome contains known variants of concern (VOC). Additionally, CovidPhy allows searching for variants and haplotypes introduced by the user and includes a list of genomes that are good candidates for being responsible for large outbreaks worldwide, most likely mediated by important superspreading events, indicating their possible geographic epicenters and their relative impact as recorded in the GISAID database.
MeSH term(s)	COVID-19/virology ; Databases, Genetic ; Genome, Viral ; Humans ; Internet ; Pandemics ; Phylogeny ; Phylogeography ; SARS-CoV-2/genetics ; Software
Language	English
Publishing date	2021-08-20
Publishing country	Netherlands
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	205699-9
ISSN	1096-0953 ; 0013-9351
ISSN (online)	1096-0953
ISSN	0013-9351
DOI	10.1016/j.envres.2021.111909
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Biogeographical informativeness of Y-STR haplotypes.

Pardo-Seco, Jacobo / Gómez-Carballa, Alberto / Bello, Xabier / Martinón-Torres, Federico / Salas, Antonio

Science bulletin

2019 Volume 64, Issue 19, Page(s) 1381–1384

Language	English
Publishing date	2019-07-26
Publishing country	Netherlands
Document type	Journal Article
ZDB-ID	2816140-3
ISSN	2095-9281 ; 2095-9273
ISSN (online)	2095-9281
ISSN	2095-9273
DOI	10.1016/j.scib.2019.07.025
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A Meta-Analysis of Multiple Whole Blood Gene Expression Data Unveils a Diagnostic Host-Response Transcript Signature for Respiratory Syncytial Virus.

Barral-Arca, Ruth / Gómez-Carballa, Alberto / Cebey-López, Miriam / Bello, Xabier / Martinón-Torres, Federico / Salas, Antonio

International journal of molecular sciences

2020 Volume 21, Issue 5

Abstract: Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. ... ...

Abstract	Respiratory syncytial virus (RSV) is one of the major causes of acute lower respiratory tract infection worldwide. The absence of a commercial vaccine and the limited success of current therapeutic strategies against RSV make further research necessary. We used a multi-cohort analysis approach to investigate host transcriptomic biomarkers and shed further light on the molecular mechanism underlying RSV-host interactions. We meta-analyzed seven transcriptome microarray studies from the public Gene Expression Omnibus (GEO) repository containing a total of 922 samples, including RSV, healthy controls, coronaviruses, enteroviruses, influenzas, rhinoviruses, and coinfections, from both adult and pediatric patients. We identified > 1500 genes differentially expressed when comparing the transcriptomes of RSV-infected patients against healthy controls. Functional enrichment analysis showed several pathways significantly altered, including immunologic response mediated by RSV infection, pattern recognition receptors, cell cycle, and olfactory signaling. In addition, we identified a minimal 17-transcript host signature specific for RSV infection by comparing transcriptomic profiles against other respiratory viruses. These multi-genic signatures might help to investigate future drug targets against RSV infection.
MeSH term(s)	Biomarkers/blood ; Case-Control Studies ; Cohort Studies ; Gene Expression Profiling ; Host-Pathogen Interactions/genetics ; Humans ; Respiratory Syncytial Virus Infections/virology ; Respiratory Syncytial Virus, Human/isolation & purification ; Respiratory Tract Infections/blood ; Respiratory Tract Infections/genetics ; Respiratory Tract Infections/virology ; Signal Transduction ; Transcriptome
Chemical Substances	Biomarkers
Keywords	covid19
Language	English
Publishing date	2020-03-06
Publishing country	Switzerland
Document type	Journal Article ; Meta-Analysis
ZDB-ID	2019364-6
ISSN	1422-0067 ; 1422-0067 ; 1661-6596
ISSN (online)	1422-0067
ISSN	1422-0067 ; 1661-6596
DOI	10.3390/ijms21051831
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Phylogeography of SARS-CoV-2 pandemic in Spain: a story of multiple introductions, micro-geographic stratification, founder effects, and super-spreaders.

Gómez-Carballa, Alberto / Bello, Xabier / Pardo-Seco, Jacobo / Pérez Del Molino, María Luisa / Martinón-Torres, Federico / Salas, Antonio

Zoological research

2020 Volume 41, Issue 6, Page(s) 605–620

Abstract: Spain has been one of the main global pandemic epicenters for coronavirus disease 2019 (COVID-19). Here, we analyzed >41 000 genomes (including >26 000 high-quality (HQ) genomes) downloaded from the GISAID repository, including 1 245 (922 HQ) sampled in ... ...

Abstract	Spain has been one of the main global pandemic epicenters for coronavirus disease 2019 (COVID-19). Here, we analyzed >41 000 genomes (including >26 000 high-quality (HQ) genomes) downloaded from the GISAID repository, including 1 245 (922 HQ) sampled in Spain. The aim of this study was to investigate genome variation of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and reconstruct phylogeographic and transmission patterns in Spain. Phylogeographic analysis suggested at least 34 independent introductions of SARS-CoV-2 to Spain at the beginning of the outbreak. Six lineages spread very successfully in the country, probably favored by super-spreaders, namely, A2a4 (7.8%), A2a5 (38.4%), A2a10 (2.8%), B3a (30.1%), and B9 (8.7%), which accounted for 87.9% of all genomes in the Spanish database. One distinct feature of the Spanish SARS-CoV-2 genomes was the higher frequency of B lineages (39.3%, mainly B3a+B9) than found in any other European country. While B3a, B9, (and an important sub-lineage of A2a5, namely, A2a5c) most likely originated in Spain, the other three haplogroups were imported from other European locations. The B3a strain may have originated in the Basque Country from a B3 ancestor of uncertain geographic origin, whereas B9 likely emerged in Madrid. The time of the most recent common ancestor (TMRCA) of SARS-CoV-2 suggested that the first coronavirus entered the country around 11 February 2020, as estimated from the TMRCA of B3a, the first lineage detected in the country. Moreover, earlier claims that the D614G mutation is associated to higher transmissibility is not consistent with the very high prevalence of COVID-19 in Spain when compared to other countries with lower disease incidence but much higher frequency of this mutation (56.4% in Spain vs. 82.4% in rest of Europe). Instead, the data support a major role of genetic drift in modeling the micro-geographic stratification of virus strains across the country as well as the role of SARS-CoV-2 super-spreaders.
MeSH term(s)	Animals ; Betacoronavirus/classification ; Betacoronavirus/genetics ; Betacoronavirus/physiology ; COVID-19 ; Coronavirus Infections/epidemiology ; Coronavirus Infections/transmission ; Coronavirus Infections/virology ; Evolution, Molecular ; Founder Effect ; Genetic Variation ; Genome, Viral/genetics ; Geography ; Haplotypes ; Humans ; Mutation ; Pandemics ; Phylogeny ; Phylogeography ; Pneumonia, Viral/epidemiology ; Pneumonia, Viral/transmission ; Pneumonia, Viral/virology ; SARS-CoV-2 ; Spain/epidemiology
Keywords	covid19
Language	English
Publishing date	2020-09-23
Publishing country	China
Document type	Journal Article
ISSN	2095-8137
ISSN	2095-8137
DOI	10.24272/j.issn.2095-8137.2020.217
Database	MEDical Literature Analysis and Retrieval System OnLINE

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