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

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

Zoological Research, Vol 42, Iss 1, Pp 87-

2021 Volume 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.
Keywords	sars-cov-2 ; covid-19 ; phylogeny ; phylodynamics ; barcode ; informative subtype markers ; Zoology ; QL1-991
Subject code	572
Language	English
Publishing date	2021-01-01T00:00:00Z
Publisher	Science Press, PR China
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A Timeframe for SARS-CoV-2 Genomes

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

International Journal of Molecular Sciences, Vol 23, Iss 12899, p

A Proof of Concept for Postmortem Interval Estimations

2022 Volume 12899

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]; t E-QG ) can be easily predicted using a phylogenetic model based on a robust reference genome database of the virus, and information on their sampling dates. We evaluate several phylogeny-based approaches, including modeling evolutionary (substitution) rates of the SARS-CoV-2 genome (~10 −3 substitutions/nucleotide/year) and the mutational (substitutions) differences separating the QGs from the reference genomes (RGs) in the database. Owing to the mutational characteristics of the virus, the present Viral Molecular Clock Dating (VMCD) method covers timeframes going backwards from about a month in the past. The method has very low errors associated to the t E-QG estimates and narrow intervals of t E-QG , both ranging from a few days to a few weeks regardless of the mathematical model used. The SARS-CoV-2 model represents a proof of concept that can be extrapolated to any other microorganism, provided that a robust genome sequence database is available. Besides obvious applications in epidemiology and microbiology investigations, there are several contexts in forensic casework where estimating t E-QG could be useful, including estimation of the postmortem intervals (PMI) and the dating of samples stored in hospital settings.
Keywords	SARS-CoV-2 ; phylogeny ; legal medicine ; molecular clock ; postmortem interval ; forensic genetics ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	333
Language	English
Publishing date	2022-10-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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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

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

International Journal of Molecular Sciences, Vol 22, Iss 3148, p

A Multi-Cohort Analysis

2021 Volume 3148

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- ( n = 695) and bacteria- ( n = 514) infected patients. We applied a Parallel Regularized Regression Model Search (PReMS) on a set of previously reported genes that distinguished viral from bacterial infection to find a minimum gene expression bio-signature. This strategy allowed us to detect three genes, namely BAFT , ISG15 and DNMT1 , that clearly differentiate groups of infection with high accuracy (training set: area under the curve (AUC) 0.86 (sensitivity: 0.81; specificity: 0.87); testing set: AUC 0.87 (sensitivity: 0.82; specificity: 0.86)). BAFT and ISG15 are involved in processes related to immune response, while DNMT1 is related to the preservation of methylation patterns, and its expression is modulated by pathogen infections. We successfully tested this three-transcript signature in the 11 independent studies, demonstrating its high performance under different scenarios. The main advantage of this three-gene signature is the low number of genes needed to differentiate both groups of patient categories.
Keywords	RNA ; RNAseq ; microarrays ; transcriptome ; transcriptomic biomarkers ; RNA signature ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2021-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multi-tissue transcriptomics of a unique monozygotic discordant twin case of severe progressive osseous heteroplasia

Alberto Gómez-Carballa / María José Currás-Tuala / Sara Pischedda / Miriam Cebey-López / José Gómez-Rial / Irene Rivero-Calle / Jacobo Pardo-Seco / Xabier Bello / Sandra Viz-Lasheras / Antonio Justicia-Grande / Julián Montoto-Louzao / Alba Camino-Mera / Isabel Ferreirós-Vidal / Máximo Fraga / José R. Antúnez / Rodolfo Gómez / Federico Martinón-Torres / Antonio Salas

Genes and Diseases, Vol 11, Iss 3, Pp 100981- (2024)

2024

Keywords	Medicine (General) ; R5-920 ; Genetics ; QH426-470
Language	English
Publishing date	2024-05-01T00:00:00Z
Publisher	KeAi Communications Co., Ltd.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Phylogeography of SARS-CoV-2 pandemic in Spain

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

Zoological Research, Vol 41, Iss 6, Pp 605-

a story of multiple introductions, micro-geographic stratification, founder effects, and super-spreaders

2020 Volume 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.
Keywords	covid-19 ; sars-cov-2 ; genomics ; phylogeny ; phylogeography ; Zoology ; QL1-991
Language	English
Publishing date	2020-11-01T00:00:00Z
Publisher	Science Press, PR China
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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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

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

International Journal of Molecular Sciences, Vol 21, Iss 5, p

2020 Volume 1831

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.
Keywords	meta-analysis ; rna ; transcriptomic ; rsv ; respiratory syncytial virus ; array ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	572
Language	English
Publishing date	2020-03-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Music compensates for altered gene expression in age-related cognitive disorders

Alberto Gómez-Carballa / Laura Navarro / Jacobo Pardo-Seco / Xabier Bello / Sara Pischedda / Sandra Viz-Lasheras / Alba Camino-Mera / María José Currás / Isabel Ferreirós / Narmeen Mallah / Sara Rey-Vázquez / Lorenzo Redondo / Ana Dacosta-Urbieta / Fernando Caamaño-Viña / Irene Rivero-Calle / Carmen Rodriguez-Tenreiro / Federico Martinón-Torres / Antonio Salas

Scientific Reports, Vol 13, Iss 1, Pp 1-

2023 Volume 15

Abstract: Abstract Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, ... ...

Abstract	Abstract Extensive literature has explored the beneficial effects of music in age-related cognitive disorders (ACD), but limited knowledge exists regarding its impact on gene expression. We analyzed transcriptomes of ACD patients and healthy controls, pre-post a music session (n = 60), and main genes/pathways were compared to those dysregulated in mild cognitive impairment (MCI) and Alzheimer’s disease (AD) as revealed by a multi-cohort study (n = 1269 MCI/AD and controls). Music was associated with 2.3 times more whole-genome gene expression, particularly on neurodegeneration-related genes, in ACD than in controls. Co-expressed gene-modules and pathways analysis demonstrated that music impacted autophagy, vesicle and endosome organization, biological processes commonly dysregulated in MCI/AD. Notably, the data indicated a strong negative correlation between musically-modified genes/pathways in ACD and those dysregulated in MCI/AD. These findings highlight the compensatory effect of music on genes/biological processes affected in MCI/AD, providing insights into the molecular mechanisms underlying the benefits of music on these disorders.
Keywords	Medicine ; R ; Science ; Q
Subject code	780
Language	English
Publishing date	2023-12-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: RNA-Seq Data-Mining Allows the Discovery of Two Long Non-Coding RNA Biomarkers of Viral Infection in Humans

Ruth Barral-Arca / Alberto Gómez-Carballa / Miriam Cebey-López / María José Currás-Tuala / Sara Pischedda / Sandra Viz-Lasheras / Xabier Bello / Federico Martinón-Torres / Antonio Salas

International Journal of Molecular Sciences, Vol 21, Iss 2748, p

2020 Volume 2748

Abstract: There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by ... ...

Abstract	There is a growing interest in unraveling gene expression mechanisms leading to viral host invasion and infection progression. Current findings reveal that long non-coding RNAs (lncRNAs) are implicated in the regulation of the immune system by influencing gene expression through a wide range of mechanisms. By mining whole-transcriptome shotgun sequencing (RNA-seq) data using machine learning approaches, we detected two lncRNAs (ENSG00000254680 and ENSG00000273149) that are downregulated in a wide range of viral infections and different cell types, including blood monocluclear cells, umbilical vein endothelial cells, and dermal fibroblasts. The efficiency of these two lncRNAs was positively validated in different viral phenotypic scenarios. These two lncRNAs showed a strong downregulation in virus-infected patients when compared to healthy control transcriptomes, indicating that these biomarkers are promising targets for infection diagnosis. To the best of our knowledge, this is the very first study using host lncRNAs biomarkers for the diagnosis of human viral infections.
Keywords	biomarkers ; RNA-seq ; lncRNA ; virus ; machine learning ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
Subject code	570
Language	English
Publishing date	2020-04-01T00:00:00Z
Publisher	MDPI AG
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Widespread evidence for horizontal transfer of transposable elements across Drosophila genomes

Genome biology. 2009 Feb., v. 10, no. 2

2009

Abstract: BACKGROUND: Horizontal transfer (HT) could play an important role in the long-term persistence of transposable elements (TEs) because it provides them with the possibility to avoid the checking effects of host-silencing mechanisms and natural selection, ... ...

Abstract	BACKGROUND: Horizontal transfer (HT) could play an important role in the long-term persistence of transposable elements (TEs) because it provides them with the possibility to avoid the checking effects of host-silencing mechanisms and natural selection, which would eventually drive their elimination from the genome. However, despite the increasing evidence for HT of TEs, its rate of occurrence among the TE pools of model eukaryotic organisms is still unknown. RESULTS: We have extracted and compared the nucleotide sequences of all potentially functional autonomous TEs present in the genomes of Drosophila melanogaster, D. simulans and D. yakuba - 1,436 insertions classified into 141 distinct families - and show that a large fraction of the families found in two or more species display levels of genetic divergence and within-species diversity that are significantly lower than expected by assuming copy-number equilibrium and vertical transmission, and consistent with a recent origin by HT. Long terminal repeat (LTR) retrotransposons form nearly 90% of the HT cases detected. HT footprints are also frequent among DNA transposons (40% of families compared) but rare among non-LTR retroelements (6%). Our results suggest a genomic rate of 0.04 HT events per family per million years between the three species studied, as well as significant variation between major classes of elements. CONCLUSIONS: The genome-wide patterns of sequence diversity of the active autonomous TEs in the genomes of D. melanogaster, D. simulans and D. yakuba suggest that one-third of the TE families originated by recent HT between these species. This result emphasizes the important role of horizontal transmission in the natural history of Drosophila TEs.
Keywords	DNA ; Drosophila melanogaster ; genetic variation ; genome ; natural history ; natural selection ; retrotransposons ; sequence diversity ; terminal repeat sequences ; transposons
Language	English
Dates of publication	2009-02
Size	p. 2172.
Publishing place	Springer-Verlag
Document type	Article
ZDB-ID	2040529-7
ISSN	1474-760X ; 1465-6914 ; 1465-6906
ISSN (online)	1474-760X ; 1465-6914
ISSN	1465-6906
DOI	10.1186/gb-2009-10-2-r22
Database	NAL-Catalogue (AGRICOLA)

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Article: Screening of repetitive motifs inside the genome of the flat oyster (Ostrea edulis): Transposable elements and short tandem repeats

Vera, Manuel / Belen G. Pardo / Carolina Bartolomé / Jeanette E.L. Carlsson / Jens Carlsson / Jose-Antonio Álvarez-Dios / Laura Sánchez / Paulino Martinez / Xabier Bello / Xulio Maside

Marine genomics. 2015 Dec., v. 24

2015

Abstract: The flat oyster (Ostrea edulis) is one of the most appreciated molluscs in Europe, but its production has been greatly reduced by the parasite Bonamia ostreae. Here, new generation genomic resources were used to analyse the repetitive fraction of the ... ...

Abstract	The flat oyster (Ostrea edulis) is one of the most appreciated molluscs in Europe, but its production has been greatly reduced by the parasite Bonamia ostreae. Here, new generation genomic resources were used to analyse the repetitive fraction of the oyster genome, with the aim of developing molecular markers to face this main oyster production challenge. The resulting oyster database, consists of two sets of 10,318 and 7159 unique contigs (4.8Mbp and 6.8Mbp in total length) representing the oyster's genome (WG) and haemocyte transcriptome (HT), respectively. A total of 1083 sequences were identified as TE-derived, which corresponded to 4.0% of WG and 1.1% of HT. They were clustered into 142 homology groups, most of which were assigned to the Penelope order of retrotransposons, and to the Helitron and TIR DNA-transposons. Simple repeats and rRNA pseudogenes, also made a significant contribution to the oyster's genome (0.5% and 0.3% of WG and HT, respectively).The most frequent short tandem repeats identified in WG were tetranucleotide motifs while trinucleotide motifs were in HT. Forty identified microsatellite loci, 20 from each database, were selected for technical validation. Success was much lower among WG than HT microsatellites (15% vs 55%), which could reflect higher variation in anonymous regions interfering with primer annealing. All microsatellites developed adjusted to Hardy–Weinberg proportions and represent a useful tool to support future breeding programmes and to manage genetic resources of natural flat oyster beds.
Keywords	Bonamia ostreae ; breeding ; databases ; genetic markers ; hemocytes ; microsatellite repeats ; nucleic acid annealing ; Ostrea edulis ; oysters ; parasites ; Penelope ; pseudogenes ; retrotransposons ; ribosomal RNA ; screening ; transcriptome ; transposons ; Europe
Language	English
Dates of publication	2015-12
Size	p. 335-341.
Publishing place	Elsevier B.V.
Document type	Article
ZDB-ID	2429626-0
ISSN	1876-7478 ; 1874-7787
ISSN (online)	1876-7478
ISSN	1874-7787
DOI	10.1016/j.margen.2015.08.006
Database	NAL-Catalogue (AGRICOLA)

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