Highly accurate whole-genome imputation of SARS-CoV-2 from partial or low-quality sequences

[Background] The current SARS-CoV-2 pandemic has emphasized the utility of viral whole-genome sequencing in the surveillance and control of the pathogen. An unprecedented ongoing global initiative is producing hundreds of thousands of sequences worldwide. However, the complex circumstances in which viruses are sequenced, along with the demand of urgent results, causes a high rate of incomplete and, therefore, useless sequences. Viral sequences evolve in the context of a complex phylogeny and different positions along the genome are in linkage disequilibrium. Therefore, an imputation method would be able to predict missing positions from the available sequencing data.[Results] We have developed the impuSARS application, which takes advantage of the enormous number of SARS-CoV-2 genomes available, using a reference panel containing 239,301 sequences, to produce missing data imputation in viral genomes. ImpuSARS was tested in a wide range of conditions (continuous fragments, amplicons or sparse individual positions missing), showing great fidelity when reconstructing the original sequences, recovering the lineage with a 100% precision for almost all the lineages, even in very poorly covered genomes (<20%).[Conclusions] Imputation can improve the pace of SARS-CoV-2 sequencing production by recovering many incomplete or low-quality sequences that would be otherwise discarded. ImpuSARS can be incorporated in any primary data processing pipeline for SARS-CoV-2 whole-genome sequencing.This work is supported by grant PT17/0009/0006 from the Spanish Ministry of Economy and Competitiveness, COVID-0012–2020 from Consejería de Salud y Familias, Junta de Andalucía, and postdoctoral contract PAIDI2020- DOC_00350 for C.L., from Junta de Andalucía, co-funded by the European Social Fund (FSE) 2014–2020.Peer reviewe

The natural is political. The construction of the environment as an object of government in the Andalusian context (1978-1989)

Entre 1978 y 1989 se crea en Andalucía un modelo de conservación ambiental que se convertirá en referente a nivel estatal e internacional. Será el resultado de un complejo proceso político marcado por tendencias contradictorias (tránsito del franquismo al parlamentarismo, del centralismo al autonomismo), activismo social-ambientalista y pugnas entre corporativismos disciplinarios (biología, ingeniería, geografía). A partir de entrevistas cualitativas, fuentes hemerográficas y documentales, explicamos este modelo, su visión y dispositivos como un marco político-administrativo que surge de relaciones personales y de la confrontación entre corrientes dentro del partido de gobierno en Andalucía (PSOE) en el contexto de un ascenso de las demandas y el movimiento ecologistas.Between 1978 and 1989, a nationally and internationally acclaimed nature conservation model was created in Andalusia. It would be the result of a complex political process, marked by contradictory tendencies (the transition from Francoism to parliamentarism, from centralism to autonomy), social-environmental activism, and disputes among professional disciplines (biology, engineering, geography, among others). Using qualitative interviews, hemerographic and documentary sources, we explain this model, its vision and instruments, as a political-administrative apparatus that result from personal relationships and the confrontation between political currents within the ruling party in Andalusia (PSOE) in the context of rising environmentalist demands and movement

Desarrollo de un entorno integrado para un computador didáctico elemental, para la asignatura de Fundamentos de Informática del nuevo grado en Ingeniería de Tecnologías de Telecomunicación

El objetivo principal de este trabajo es la potenciación y mejora de la metodología docente en la asignatura de Fundamentos de Informática, asignatura obligatoria correspondiente al nuevo Grado en Ingeniería de Tecnologías de Telecomunicación de la Universidad de Granada. Para ello, se ha desarrollado un entorno integrado didáctico que engloba, en una sola aplicación, tanto el simulador como el ensamblador de un Computador Didáctico Elemental desarrollado en nuestro departamento, CODE-2, y que, además, incorpora un programa editor y un ensamblador en línea con el que el alumno puede visualizar directamente el código máquina generado por el código ensamblador que está escribiendo en tiempo real. De esta forma, conseguimos facilitar que los alumnos puedan adquirir los conocimientos necesarios para comprender el funcionamiento interno de un computador.Subvencionado parcialmente por el proyecto de Innovación Docente 10-22 de la Universidad de Granad

SARS-CoV-2 genome sequencing in Andalusia, methodology and study of variants

La incorporación de las técnicas de secuenciación genómica mediante secuenciación de nueva generación ha revolucionado la microbiología clínica, innovando y mejorando el diagnóstico clínico de las enfermedades infecciosas. Hoy en día, la secuenciación de genoma completo en enfermedades infecciosas tiene multitud de aplicaciones en virología, bacteriología, resistencia antibiótica, epidemiología y salud pública. Con la aparición del SARS-CoV-2, se ha visto subrayada la importancia del análisis y estudio de las secuencias genéticas. Desde la identificación inicial del SARS-CoV-2, hasta la fecha, se han compartido, a nivel mundial, más de 414.575 secuencias genómicas completas a través de bases de datos de acceso público. La capacidad de monitorizar la evolución viral casi en tiempo real tiene un impacto directo en la respuesta de salud pública a la pandemia de COVID-19. En este trabajo se presenta la importancia de la secuenciación genómica en microbiología, enfermedades infecciosas, epidemiología y salud pública, y se describe cómo se ha implementado la secuenciación de SARS-CoV-2 en Andalucía, y cuales son los principales resultados hasta la fecha.The incorporation of genomic sequencing techniques through next-generation sequencing has revolutionized clinical microbiology, innovating and improving the clinical diagnosis of infectious diseases. Today, whole genome sequencing in infectious diseases has many applications in virology, bacteriology, antibiotic resistance, epidemiology, and public health. With the appearance of SARS-CoV-2, the importance of the analysis and study of genetic sequences has been underlined. Since the initial identification of SARS-CoV-2, to date, more than 414,575 complete genomic sequences have been shared worldwide through public access databases. The ability to monitor viral evolution in near real time has a direct impact on the public health response to the COVID-19 pandemic. This paper presents the importance of genomic sequencing in microbiology, infectious diseases, epidemiology and public health, and describes how SARS-CoV-2 sequencing has been implemented in Andalusia, and what the main results are to date

CSVS, a crowdsourcing database of the Spanish population genetic variability

The knowledge of the genetic variability of the local population is of utmost importance in personalized medicine and has been revealed as a critical factor for the discovery of new disease variants. Here, we present the Collaborative Spanish Variability Server (CSVS), which currently contains more than 2000 genomes and exomes of unrelated Spanish individuals. This database has been generated in a collaborative crowdsourcing effort collecting sequencing data produced by local genomic projects and for other purposes. Sequences have been grouped by ICD10 upper categories. A web interface allows querying the database removing one or more ICD10 categories. In this way, aggregated counts of allele frequencies of the pseudo-control Spanish population can be obtained for diseases belonging to the category removed. Interestingly, in addition to pseudo-control studies, some population studies can be made, as, for example, prevalence of pharmacogenomic variants, etc. In addition, this genomic data has been used to define the first Spanish Genome Reference Panel (SGRP1.0) for imputation. This is the first local repository of variability entirely produced by a crowdsourcing effort and constitutes an example for future initiatives to characterize local variabilityworldwide. CSVS is also part of the GA4GH Beacon network.Spanish Ministry of Economy and Competitiveness SAF2017-88908-R PT17/0009/0006 PI19/00321 CIBERER ACCI-06/07/0036 PI14-948 PI171659Regional Government of Madrid, RAREGenomicsCM B2017/BMD3721 B2017/BMD-3721European Union (EU)European Union (EU) 676559University Chair UAM-IIS-FJD of Genomic MedicineRamon Areces Foundatio

Assessing the Impact of SARS-CoV-2 Lineages and Mutations on Patient Survival

Objectives: More than two years into the COVID-19 pandemic, SARS-CoV-2 still remains a global public health problem. Successive waves of infection have produced new SARS-CoV-2 variants with new mutations for which the impact on COVID-19 severity and patient survival is uncertain. Methods: A total of 764 SARS-CoV-2 genomes, sequenced from COVID-19 patients, hospitalized from 19th February 2020 to 30 April 2021, along with their clinical data, were used for survival analysis. Results: A significant association of B.1.1.7, the alpha lineage, with patient mortality (log hazard ratio (LHR) = 0.51, C.I. = [0.14,0.88]) was found upon adjustment by all the covariates known to affect COVID-19 prognosis. Moreover, survival analysis of mutations in the SARS-CoV-2 genome revealed 27 of them were significantly associated with higher mortality of patients. Most of these mutations were located in the genes coding for the S, ORF8, and N proteins. Conclusions: This study illustrates how a combination of genomic and clinical data can provide solid evidence for the impact of viral lineage on patient survival.This work was supported by Spanish Ministry of Science and Innovation (grant PID2020- 117979RB-I00), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), and has also been funded by Consejería de Salud y Familias, Junta de Andalucía (grants COVID-0012-2020 and PS-2020-342) and the postdoctoral contract of Carlos Loucera (PAIDI2020- DOC_00350), co-funded by the European Social Fund (FSE) 2014-2020. ELIXIR-CONVERGE—H2020 (871075).Peer reviewe

Molecular and phylogenetic characterization of the monkeypox outbreak in the South of Spain

Until the May 2022 Monkeypox outbreak, which spread rapidly to many non-endemic countries, the virus was considered a viral zoonosis limited to some African countries. The Andalusian circuit of genomic surveillance was rapidly applied to characterize the Monkeypox outbreak in the South of Spain. Whole genome sequencing was used to obtain the genomic profiles of samples collected across the south of Spain, representative of all the provinces of Andalusia. Phylogenetic analysis was used to study the relationship of the isolates and the available sequences of the 2022 outbreak. Whole genome sequencing of a total of 160 monkeypox viruses from the different provinces that reported cases were obtained. Interestingly, we report the sequences of monkeypox viruses obtained from two patients who died. While one of the isolates bore no noteworthy mutations that explain a potential heightened virulence, in another patient the second consecutive genome sequence, performed after the administration of tecovirimat, uncovered a mutation within the A0A7H0DN30 gene, known to be a prime target for tecovirimat in its Vaccinia counterpart. In general, a low number of mutations were observed in the sequences reported, which were very similar to the reference of the 2022 outbreak (OX044336), as expected from a DNA virus. The samples likely correspond to several introductions of the circulating monkeypox viruses from the last outbreak. The virus sequenced from one of the two patients that died presented a mutation in a gene that bears potential connections to drug resistance. This mutation was absent in the initial sequencing prior to treatmentThis work was supported by Spanish Ministry of Science and Innovation (grants PID2020- 117979RB-I00 and FJC2021-046546-I), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), it has also been funded by Consejería de Salud y Consumo, Junta de Andalucía (grants COVID-0012-2020), and by grant ELIXIR-CONVERGE - Connect and align ELIXIR Nodes to deliver sustainable FAIR lifescience data management services (AMD-871075-16), funded by EU – H2020.N

A crowdsourcing database for the copy-number variation of the spanish population

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion: SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database.This work is supported by Grants PID2020-117979RB-I00 from the Spanish Ministry of Science and Innovation; by the Institute of Health Carlos III (project IMPaCT-Data, exp. IMP/00019, IMP/00009 and PI20/01305), co-funded by the European Union, European Regional Development Fund (ERDF, “A way to make Europe”)

Detection of High Level of Co-Infection and the Emergence of Novel SARS CoV-2 Delta-Omicron and Omicron-Omicron Recombinants in the Epidemiological Surveillance of Andalusia

Recombination is an evolutionary strategy to quickly acquire new viral properties inherited from the parental lineages. The systematic survey of the SARS-CoV-2 genome sequences of the Andalusian genomic surveillance strategy has allowed the detection of an unexpectedly high number of co-infections, which constitute the ideal scenario for the emergence of new recombinants. Whole genome sequence of SARS-CoV-2 has been carried out as part of the genomic surveillance programme. Sample sources included the main hospitals in the Andalusia region. In addition to the increase of co-infections and known recombinants, three novel SARS-CoV-2 delta-omicron and omicron-omicron recombinant variants with two break points have been detected. Our observations document an epidemiological scenario in which co-infection and recombination are detected more frequently. Finally, we describe a family case in which co-infection is followed by the detection of a recombinant made from the two co-infecting variants. This increased number of recombinants raises the risk of emergence of recombinant variants with increased transmissibility and pathogenicity.This research was funded by Spanish Ministry of Science and Innovation (grant PID2020-117979RB-I00), the Instituto de Salud Carlos III (ISCIII), co-funded with European Regional Development Funds (ERDF) (grant IMP/00019), and has also been funded by Consejería de Salud y Familias, Junta de Andalucía (grants COVID-0012-2020, PS-2020-342 and IE19_259 FPS).Peer reviewe

A crowdsourcing database for the copy-number variation of the Spanish population

Background: Despite being a very common type of genetic variation, the distribution of copy-number variations (CNVs) in the population is still poorly understood. The knowledge of the genetic variability, especially at the level of the local population, is a critical factor for distinguishing pathogenic from non-pathogenic variation in the discovery of new disease variants. Results: Here, we present the SPAnish Copy Number Alterations Collaborative Server (SPACNACS), which currently contains copy number variation profiles obtained from more than 400 genomes and exomes of unrelated Spanish individuals. By means of a collaborative crowdsourcing effort whole genome and whole exome sequencing data, produced by local genomic projects and for other purposes, is continuously collected. Once checked both, the Spanish ancestry and the lack of kinship with other individuals in the SPACNACS, the CNVs are inferred for these sequences and they are used to populate the database. A web interface allows querying the database with different filters that include ICD10 upper categories. This allows discarding samples from the disease under study and obtaining pseudo-control CNV profiles from the local population. We also show here additional studies on the local impact of CNVs in some phenotypes and on pharmacogenomic variants. SPACNACS can be accessed at: http://csvs.clinbioinfosspa.es/spacnacs/. Conclusion: SPACNACS facilitates disease gene discovery by providing detailed information of the local variability of the population and exemplifies how to reuse genomic data produced for other purposes to build a local reference database