Optimización de la Entrada Salida mediante librerías y lenguajes paralelos

Uno de los grandes retos de la HPC (High Performance Computing) consiste en optimizar el subsistema de Entrada/Salida, (E/S), o I/O (Input/Output). Ken Batcher resume este hecho en la siguiente frase: "Un supercomputador es un dispositivo que convierte los problemas limitados por la potencia de cálculo en problemas limitados por la E/S" ("A Supercomputer is a device for turning compute-bound problems into I/O-bound problems") . En otras palabras, el cuello de botella ya no reside tanto en el procesamiento de los datos como en la disponibilidad de los mismos. Además, este problema se exacerbará con la llegada del Exascale y la popularización de las aplicaciones Big Data. En este contexto, esta tesis contribuye a mejorar el rendimiento y la facilidad de uso del subsistema de E/S de los sistemas de supercomputación. Principalmente se proponen dos contribuciones al respecto: i) una interfaz de E/S desarrollada para el lenguaje Chapel que mejora la productividad del programador a la hora de codificar las operaciones de E/S; y ii) una implementación optimizada del almacenamiento de datos de secuencias genéticas. Con más detalle, la primera contribución estudia y analiza distintas optimizaciones de la E/S en Chapel, al tiempo que provee a los usuarios de una interfaz simple para el acceso paralelo y distribuido a los datos contenidos en ficheros. Por tanto, contribuimos tanto a aumentar la productividad de los desarrolladores, como a que la implementación sea lo más óptima posible. La segunda contribución también se enmarca dentro de los problemas de E/S, pero en este caso se centra en mejorar el almacenamiento de los datos de secuencias genéticas, incluyendo su compresión, y en permitir un uso eficiente de esos datos por parte de las aplicaciones existentes, permitiendo una recuperación eficiente tanto de forma secuencial como aleatoria. Adicionalmente, proponemos una implementación paralela basada en Chapel

Diseño de la adaptación de un juego de ajedrez para personas con movilidad reducida

Según el tipo de discapacidad la comunicación puede ser una gran perdida de tiempo debido a la dificultad de habla y ocasionaría la perdida de la partida por tiempo. Por ello se propone el diseño de un tablero de ajedrez donde el propio jugador escoja mediante un mando (ya sea mediante un joystick o a través de un acelerómetro) la pieza que quiere mover y donde, y una vez seleccionado el tiempo de este jugador se detendrá unos segundos para permitir al ayudante mover la ficha. No solo evitará perder más tiempo del necesario sino que mejorará la comunicación entre jugador y ayudante facilitando la tarea de este ultimo

miRNA as biomarker in lung cancer

Lung cancer has a high prevalence and mortality due to its late diagnosis and limited treatment, so it is essential to find biomarkers that allow a faster diagnosis and improve the survival of these patients. In this sense, biomarkers based on miRNAs have supposed a considerable advance. miRNAs, which are small RNA sequences, can regulate gene expression, so they play an essential role not only as a diagnostic biomarker but also as a therapeutic and prognostic one. Also, miRNA biomarkers can be obtained from liquid biopsies, which are less intrusive than lung biopsies, and have better accessibil-ity, safety and repeatability, which allows using those biomarkers both for diagnosis and monitoring of patients. In this review, we highlight the importance of miRNAs and collect the existing evidence of their relationship with lung cancer.Funding for open access charge: Universidad de Málaga / CBUA Funding for open access publishing: Universidad Málaga / CBU

Comparing assembly strategies for third-generation sequencing technologies across different genomes

The recent advent of long-read sequencing technologies, such as Pacific Biosciences (PacBio) and Oxford Nanopore technology (ONT), has led to substantial accuracy and computational cost improvements. However, de novo whole-genome assembly still presents significant challenges related to the computational cost and the quality of the results. Accordingly, sequencing accuracy and throughput continue to improve, and many tools are constantly emerging. Therefore, selecting the correct sequencing platform, the proper sequencing depth and the assembly tools are necessary to perform high-quality assembly. This paper evaluates the primary assembly reconstruction from recent hybrid and non-hybrid pipelines on different genomes. We find that using PacBio high-fidelity long-read (HiFi) plays an essential role in haplotype construction with respect to ONT reads. However, we observe a substantial improvement in the correctness of the assembly from high-fidelity ONT datasets and combining it with HiFi or short-reads.This work has been partially supported by the Spanish MINECO PID2019-105396RB-I00, Junta de Andalucia JA2018 P18-FR-3433, and UMA18-FEDERJA-197 projects. Funding for open access charge: Universidad de Málaga/CBUA.Peer ReviewedPostprint (published version

Comparing assembly strategies for third-generation sequencing technologies across different genomes

The recent advent of long-read sequencing technologies, such as Pacific Biosciences (PacBio) and Oxford Nanopore technology (ONT), has led to substantial accuracy and computational cost improvements. However, de novo whole-genome assembly still presents significant challenges related to the computational cost and the quality of the results. Accordingly, sequencing accuracy and throughput continue to improve, and many tools are constantly emerging. Therefore, selecting the correct sequencing platform, the proper sequencing depth and the assembly tools are necessary to perform high-quality assembly. This paper evaluates the primary assembly reconstruction from recent hybrid and non-hybrid pipelines on different genomes. We find that using PacBio high-fidelity long-read (HiFi) plays an essential role in haplotype construction with respect to ONT reads. However, we observe a substantial improvement in the correctness of the assembly from high-fidelity ONT datasets and combining it with HiFi or short-reads.Funding for open access charge: Universidad de Málaga / CBU

A systematic literature review and expert consensus on risk factors associated to infection progression in adult patients with respiratory tract or rectal colonisation by carbapenem-resistant Gram-negative bacteria

Multi-drug resistance; Risk factor; ColonizationResistencia a múltiples fármacos; Factor de riesgo; ColonizaciónResistència a múltiples fàrmacs; Factor de risc; ColonitzacióObjective. Risk factors (RFs) associated with infection progression in patients already colonised by carbapenem-resistant Gram-negative bacteria (CRGNB) have been addressed in few and disperse works. The aim of this study is to identify the relevant RFs associated to infection progression in patients with respiratory tract or rectal colonisation. Material and methods. A systematic literature review was developed to identify RFs associated with infection progression in patients with CRGNB respiratory tract or rectal colonisation. Identified RFs were then evaluated and discussed by the expert panel to identify those that are relevant according to the evidence and expert’s experience. Results. A total of 8 articles were included for the CRGNB respiratory tract colonisation and 21 for CRGNB rectal colonisation, identifying 19 RFs associated with pneumonia development and 44 RFs associated with infection progression, respectively. After discussion, the experts agreed on 13 RFs to be associated with pneumonia development after respiratory tract CRGNB colonisation and 33 RFs to be associated with infection progression after rectal CRGNB colonisation. Respiratory tract and rectal colonisation, previous stay in the ICU and longer stay in the ICU were classified as relevant RF independently of the pathogen and site of colonisation. Previous exposure to antibiotic therapy or previous carbapenem use were also common relevant RF for patients with CRGNB respiratory tract and rectal colonisation. Conclusion. The results of this study may contribute to the early identification of CRGNB colonized patients at higher risk of infection development, favouring time-to-effective therapy and improving health outcomes.This study was funded by Shionogi S.L.U

Whole-Genome Assembly: An Experimental Study of Computational Costs and Architectural Opportunities

Whole-genome sequencing (WGS) pro- vides a huge amount of reads from which a comple- te genome could be assembled. The recent advent of long read sequencing technologies, such as PacBio and Oxford Nanopore, and the subsequent appearance of high quality long reads (single molecule high-fidelity, or HiFi) have improved the scaffolding of the genome. However, both biology and computing communities still face great challenges in terms of computational cost. Thus, it is essential a high precision characte- rization of the methods for a correct identification of the main computing bottlenecks. This study will allow us to design new methods to mitigate compu- tational costs without losing accuracy and to adapt such methods to fully exploit new architectures that provide support to handle big amounts of data. In this paper, we experimentally study and characterize the most used whole-genome assemblers in order to design new approaches in this field.Universidad de Málaga. Campus de Excelencia Internacional Andalucía Tech

A systematic review and expert’s analysis of risk factors of infections in adults due to carbapenem-resistant Pseudomonas aeruginosa or Acinetobacter baumannii in Spain

Pseudomones aeruginosa; Resistència a carbapenèmics; Factor de riscPseudomonas aeruginosa; Resistencia a carbapenémicos; Factor de riesgoPseudomonas aeruginosa; Carbapenem resistance; Risk factorObjetivo. El objetivo del estudio es identificar los factores de riesgo asociados a infecciones por Pseudomonas aeruginosa resistente a antibióticos carbapenémicos (PARC) y Acinetobacter baumannii resistente a antibióticos carbapenémicos (ABRC) en pacientes adultos a través de una revisión sistemática de la literatura, clasificarlos según su nivel de importancia y exponer las recomendaciones en el entorno español de un panel de expertos. Material y métodos. Se llevó a cabo una revisión sistemática de la literatura para identificar los factores de riesgo asociados a PARC o ABRC y posteriormente evaluar cada factor de riesgo por un panel de expertos basándose en la evidencia disponible y su experiencia en la práctica clínica. Resultados. Se identificaron 593 artículos incluyéndose 29 para PARC y 23 para ABRC. Se identificaron 38 factores de riesgo asociados a PARC y 36 factores de riesgo asociados a ABRC. Tras su evaluación, para PARC, se clasificaron en: 11 importantes, 10 moderadamente importantes y 15 poco importantes; y para ABRC, 9 importantes, 5 moderadamente importantes y 19 poco importantes. Para ambos patógenos, los factores de riesgo importantes estuvieron relacionados con el uso previo de antibióticos y la hospitalización. Conclusión. Se han identificado los principales factores de riesgo asociados a PARC y ABRC mediante una revisión de la evidencia disponible. Sin embargo, son necesarios estudios adicionales prospectivos que permitan identificar los pacientes con infecciones por dichos patógenos.Objective. The aim of the study is to identify risk factors associated to infections caused by carbapenem-resistant Pseudomonas aeruginosa (CRPA) and carbapenem-resistant Acinetobacter baumannii (CRAB) in adult patients through a systematic literature review, classify them according to their importance and provide recommendations by experts in the Spanish context. Material and methods. We developed a systematic literature review to identify risk factors associated to CRPA or CRAB infections and they were evaluated and discussed by a multidisciplinary panel of experts. Results. There were included 29 studies for P. aeruginosa and 23 for A. baumannii out of 593 identified through systematic literature review. We identified 38 risk factors for P. aeruginosa and 36 for A. baumannii. After risk factor evaluation by the panel of experts, results for CRPA were: 11 important, 10 slightly important and 15 unimportant risk factors; and for CRAB were: 9 important, 5 slightly important and 19 unimportant risk factors. For both pathogens, previous use of antibiotics and hospitalization were important risk factors. Conclusion. We could identify the main risk factors associated to CRPA and CRAB through literature review. There is a need for developing additional studies with higher levels of evidence to identify sooner and better infected patients through associated risk factors.El desarrollo de este estudio se llevó a cabo por Omakase Consulting y un panel de expertos español, con la financiación de Shionogi España. La redacción del manuscrito se ha realizado por Omakase Consulting bajo la dirección del panel de expertos, con la financiación de Shionogi España

Pseudomonas aeruginosa antibiotic susceptibility profiles, genomic epidemiology and resistance mechanisms: a nation-wide five-year time lapse analysis

Background: Pseudomonas aeruginosa healthcare-associated infections are one of the top antimicrobial resistance threats world-wide. In order to analyze the current trends, we performed a Spanish nation-wide high-resolution analysis of the susceptibility profiles, the genomic epidemiology and the resistome of P. aeruginosa over a five-year time lapse. Methods: A total of 3.180 nonduplicated P. aeruginosa clinical isolates from two Spanish nation-wide surveys performed in October 2017 and 2022 were analyzed. MICs of 13 antipseudomonals were determined by ISO-EUCAST. Multidrug resistance (MDR)/extensively drug resistance (XDR)/difficult to treat resistance (DTR)/pandrug resistance (PDR) profiles were defined following established criteria. All XDR/DTR isolates were subjected to whole genome sequencing (WGS). Findings: A decrease in resistance to all tested antibiotics, including older and newer antimicrobials, was observed in 2022 vs 2017. Likewise, a major reduction of XDR (15.2% vs 5.9%) and DTR (4.2 vs 2.1%) profiles was evidenced, and even more patent among ICU isolates [XDR (26.0% vs 6.0%) and DTR (8.9% vs 2.6%)] (p < 0.001). The prevalence of Extended-spectrum β-lactamase/carbapenemase production was slightly lower in 2022 (2.1%. vs 3.1%, p = 0.064). However, there was a significant increase in the proportion of carbapenemase production among carbapenem-resistant strains (29.4% vs 18.1%, p = 0.0246). While ST175 was still the most frequent clone among XDR, a slight reduction in its prevalence was noted (35.9% vs 45.5%, p = 0.106) as opposed to ST235 which increased significantly (24.3% vs 12.3%, p = 0.0062). Interpretation: While the generalized decrease in P. aeruginosa resistance, linked to a major reduction in the prevalence of XDR strains, is encouraging, the negative counterpart is the increase in the proportion of XDR strains producing carbapenemases, associated to the significant advance of the concerning world-wide disseminated hypervirulent high-risk clone ST235. Continued high-resolution surveillance, integrating phenotypic and genomic data, is necessary for understanding resistance trends and analyzing the impact of national plans on antimicrobial resistance.This work was supported by MSD and by the Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea —NextGenerationEU through grants PI21/00017 and Personalized and precision medicine grant (MePRAM Project, PMP22/00092).S

An increase in erythromycin resistance in methicillin-susceptible Staphylococcus aureus from blood correlates with the use of macrolide/lincosamide/streptogramin antibiotics. EARS-Net Spain (2004–2020)

Objectives: To describe and analyse erythromycin resistance trends in blood isolates of Staphylococcus aureus (EARS-Net Spain, 2004–2020) and the association of these trends with the consumption of macrolide, lincosamide, and streptogramin B (MLSB) antibiotics. To assess molecular changes that could be involved in erythromycin resistance trends by whole genome analysis of representative isolates. Materials and methods: We collected antibiotic susceptibility data for all firstblood S. aureus isolates in patients from 47 Spanish hospitals according to EARS-Net criteria. MLSB antibiotic consumption was obtained from the Spanish Agency for Medicines and Medical Devices (2008–2020). We sequenced 137 representative isolates for core genome multilocus sequence typing, resistome and virulome analysis. Results: For the 36,612 invasive S. aureus isolates, methicillin resistance decreased from 26.4% in 2004 to 22.4% in 2020. Erythromycin resistance in methicillin-susceptible S. aureus (MSSA) increased from 13.6% in 2004 to 28.9% in 2020 (p < 0.001); however, it decreased from 68.7 to 61.8% (p < 0.0001) in methicillin-resistant S. aureus (MRSA). Total consumption of MLSB antibiotics increased from 2.72 defined daily doses per 1,000 inhabitants per day (DID) in 2014 to 3.24 DID in 2016. By WGS, the macrolide resistance genes detected were erm (59.8%), msrA (46%), and mphC (45.2%). The erm genes were more prevalent in MSSA (44/57, 77.2%) than in MRSA (38/80, 47.5%). Most of the erm genes identified in MSSA after 2013 differed from the predominant ermC gene (17/22, 77.3%), largely because ermT was significantly associated with MSSA after 2013 (11/29, 37.9%). All 13 ermT isolates in this study, except one, belonged to ST398 and came from 10 hospitals and six Spanish provinces. Conclusion: The significant increase in erythromycin resistance in blood MSSA correlated with the consumption of the MLSB antibiotics in Spain. These preliminary data seem support the hypothesis that the human ST398 MSSA clade with ermT-mediated resistance to erythromycin may be involved in this trend.This research was supported by CIBER—Consorcio Centro de Investigación Biomédica en Red (CB21/13/00095, CB21/13/00006, CB21/13/00054, CB21/13/00068, CB21/13/00084, CB21/13/00099 groups of CIBERINFEC; CB06/06/0058 group of CIBERES), Instituto de Salud Carlos III, Ministerio de Ciencia e Innovación and Unión Europea-NextGenerationEU. This research was also supported by Personalized and precision medicine grant from the Instituto de Salud Carlos III (MePRAM Project, PMP22/00092), and by the Antibiotic Resistance and Staphylococcus aureus Surveillance Programs of the National Center for Microbiology, Instituto de Salud Carlos III.S