DISMIRA: Prioritization of disease candidates in miRNA-disease associations based on maximum weighted matching inference model and motif-based analysis

Background MicroRNAs (miRNAs) have increasingly been found to regulate diseases at a significant level. The interaction of miRNA and diseases is a complex web of multilevel interactions, given the fact that a miRNA regulates upto 50 or more diseases and miRNAs/diseases work in clusters. The clear patterns of miRNA regulations in a disease are still elusive. Methods In this work, we approach the miRNA-disease interactions from a network scientific perspective and devise two approaches - maximum weighted matching model (a graph theoretical algorithm which provides the result by solving an optimization equation of selecting the most prominent set of diseases) and motif-based analyses (which investigates the motifs of the miRNA-disease network and selects the most prominent set of diseases based on their maximum number of participation in motifs, thereby revealing the miRNA-disease interaction dynamics) to determine and prioritize the set of diseases which are most certainly impacted upon the activation of a group of queried miRNAs, in a miRNA-disease network. Results and Conclusion Our tool, DISMIRA implements the above mentioned approaches and presents an interactive visualization which helps the user in exploring the networking dynamics of miRNAs and diseases by analyzing their neighbors, paths and topological features. A set of miRNAs can be used in this analysis to get the associated diseases for the input group of miRs with ranks and also further analysis can be done to find key miRs or diseases, shortest paths etc

SIMBA: a web tool for managing bacterial genome assembly generated by Ion PGM sequencing technology

Background The evolution of Next-Generation Sequencing (NGS) has considerably reduced the cost per sequenced-base, allowing a significant rise of sequencing projects, mainly in prokaryotes. However, the range of available NGS platforms requires different strategies and software to correctly assemble genomes. Different strategies are necessary to properly complete an assembly project, in addition to the installation or modification of various software. This requires users to have significant expertise in these software and command line scripting experience on Unix platforms, besides possessing the basic expertise on methodologies and techniques for genome assembly. These difficulties often delay the complete genome assembly projects. Results In order to overcome this, we developed SIMBA (SImple Manager for Bacterial Assemblies), a freely available web tool that integrates several component tools for assembling and finishing bacterial genomes. SIMBA provides a friendly and intuitive user interface so bioinformaticians, even with low computational expertise, can work under a centralized administrative control system of assemblies managed by the assembly center head. SIMBA guides the users to execute assembly process through simple and interactive pages. SIMBA workflow was divided in three modules: (i) projects: allows a general vision of genome sequencing projects, in addition to data quality analysis and data format conversions; (ii) assemblies: allows de novo assemblies with the software Mira, Minia, Newbler and SPAdes, also assembly quality validations using QUAST software; and (iii) curation: presents methods to finishing assemblies through tools for scaffolding contigs and close gaps. We also presented a case study that validated the efficacy of SIMBA to manage bacterial assemblies projects sequenced using Ion Torrent PGM. Conclusion Besides to be a web tool for genome assembly, SIMBA is a complete genome assemblies project management system, which can be useful for managing of several projects in laboratories. SIMBA source code is available to download and install in local webservers at http://ufmg-simba.sourceforge.net

The Detection and Sequencing of a Broad-Host-Range Conjugative IncP-1 beta Plasmid in an Epidemic Strain of Mycobacterium abscessus subsp bolletii

Background: An extended outbreak of mycobacterial surgical infections occurred in Brazil during 2004-2008. Most infections were caused by a single strain of Mycobacterium abscessus subsp. bolletii, which was characterized by a specific rpoB sequevar and two highly similar pulsed-field gel electrophoresis (PFGE) patterns differentiated by the presence of a similar to 50 kb band. the nature of this band was investigated.Methodology/Principal Findings: Genomic sequencing of the prototype outbreak isolate INCQS 00594 using the SOLiD platform demonstrated the presence of a 56,264-bp circular plasmid, designated pMAB01. Identity matrices, genetic distances and phylogeny analyses indicated that pMAB01 belongs to the broad-host-range plasmid subgroup IncP-1 beta and is highly related to BRA100, pJP4, pAKD33 and pB10. the presence of pMAB01-derived sequences in 41 M. abscessus subsp. bolletii isolates was evaluated using PCR, PFGE and Southern blot hybridization. Sixteen of the 41 isolates showed the presence of the plasmid. the plasmid was visualized as a similar to 50-kb band using PFGE and Southern blot hybridization in 12 isolates. the remaining 25 isolates did not exhibit any evidence of this plasmid. the plasmid was successfully transferred to Escherichia coli by conjugation and transformation. Lateral transfer of pMAB01 to the high efficient plasmid transformation strain Mycobacterium smegmatis mc(2)155 could not be demonstrated.Conclusions/Significance: the occurrence of a broad-host-range IncP-1 beta plasmid in mycobacteria is reported for the first time. Thus, genetic exchange could result in the emergence of specific strains that might be better adapted to cause human disease.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Fundao de Amparo a Pesquisa do Estado de São PauloUniversidade Federal de São Paulo, Disciplina Microbiol, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilFed Univ Para, Inst Ciencias Biol, Lab Polimorfismo DNA, BR-66059 Belem, Para, BrazilInst Evandro Chagas, Secao Bacteriol & Micol, Ananindeua, PA, BrazilFed Univ Para, Inst Estudos Costeiros, Braganca, PA, BrazilUniv Fed Minas Gerais, Inst Ciencias Biol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Disciplina Microbiol, Dept Microbiol Imunol & Parasitol, Escola Paulista Med, São Paulo, BrazilFAPESP: FAPESP - 06/01533-9Fundao de Amparo a Pesquisa do Estado de São Paulo: FAPESP - 8/01451-8Web of Scienc

Boletim COVID-PA: relatos sobre projeções baseadas em inteligência artificial no enfrentamento da pandemia de COVID-19 no estado do Pará

Objective: Report the university research and extension product denominated ‘Boletim COVID-PA’ which presented projections about the pandemic in the State of Pará, Brazil, with practical, mathematically rigorous and computationally efficient approaches. Methods: The artificial intelligence technique known as Artificial Neural Networks was used to generate thirteen bulletins with short-term projections based on historical data from the State Department of Public Health system. Results: After eight months of projections, the technique generated reliable results with an average accuracy of 97% (147 days observed) for confirmed cases, 96% (161 observed days) for deaths and 86% (72 days observed) for occupancy of intensive care unit beds. Conclusion: These bulletins have become a useful tool for decision making by public managers, assisting in reallocating hospital resources and optimizing COVID-19 control strategies for the various regions of the State of Pará.Objetivo: Relatar o produto de pesquisa e extensão universitária denominado Boletim COVID-PA, que apresentou projeções sobre o comportamento da pandemia no estado do Pará, Brasil. Métodos: Utilizou-se da técnica de inteligência artificial conhecida como ‘redes neurais artificiais’, para gerar 13 boletins com projeções de curto prazo baseadas nos dados históricos do sistema da Secretaria de Estado de Saúde Pública. Resultados: Após oito meses de projeções, a técnica gerou resultados confiáveis, com precisão média de 97% (147 dias observados) para casos confirmados, 96% (161 dias observados) para óbitos e 86% (72 dias observados) para ocupação de leitos de unidade de terapia intensiva. Conclusão: Esses boletins tornaram-se um instrumento útil para a tomada de decisão de gestores públicos, auxiliando na realocação de recursos hospitalares e otimização das estratégias de controle da COVID-19 nas diversas regiões do estado do Pará

Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains

Ruiz JC, D'Afonseca V, Silva A, et al. Evidence for Reductive Genome Evolution and Lateral Acquisition of Virulence Functions in Two Corynebacterium pseudotuberculosis Strains. PLoS ONE. 2011;6(4): e18551.Background: Corynebacterium pseudotuberculosis, a Gram-positive, facultative intracellular pathogen, is the etiologic agent of the disease known as caseous lymphadenitis (CL). CL mainly affects small ruminants, such as goats and sheep; it also causes infections in humans, though rarely. This species is distributed worldwide, but it has the most serious economic impact in Oceania, Africa and South America. Although C. pseudotuberculosis causes major health and productivity problems for livestock, little is known about the molecular basis of its pathogenicity. Methodology and Findings: We characterized two C. pseudotuberculosis genomes (Cp1002, isolated from goats; and CpC231, isolated from sheep). Analysis of the predicted genomes showed high similarity in genomic architecture, gene content and genetic order. When C. pseudotuberculosis was compared with other Corynebacterium species, it became evident that this pathogenic species has lost numerous genes, resulting in one of the smallest genomes in the genus. Other differences that could be part of the adaptation to pathogenicity include a lower GC content, of about 52%, and a reduced gene repertoire. The C. pseudotuberculosis genome also includes seven putative pathogenicity islands, which contain several classical virulence factors, including genes for fimbrial subunits, adhesion factors, iron uptake and secreted toxins. Additionally, all of the virulence factors in the islands have characteristics that indicate horizontal transfer. Conclusions: These particular genome characteristics of C. pseudotuberculosis, as well as its acquired virulence factors in pathogenicity islands, provide evidence of its lifestyle and of the pathogenicity pathways used by this pathogen in the infection process. All genomes cited in this study are available in the NCBI Genbank database (http://www.ncbi.nlm.nih.gov/genbank/) under accession numbers CP001809 and CP001829

Genomic analysis of Klebsiella pneumoniae high-risk clone ST11 co-harbouring MCR-1.27 and KPC-2 recovered at a paediatric oncologic hospital in the Brazilian Amazon region

Evandro Chagas Institute (IEC), Secretariat for Science, Technology, Innovation and Strategic Health Inputs (SCTIE), Brazilian Ministry of Health (MS). Yan Corrêa Rodrigues’ scholarship is funded by PDPG - Pós-Doutorado Estratégico (PDPG-POSDOC), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES/ Edital 16/2022).Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Biologia Molecular. Ananindeua, PA, Brasil.Universidade Federal do Pará. Laboratório de Engenharia Biológica. Belém, PA, Brazil.Universidade Federal do Pará. Laboratório de Engenharia Biológica. Belém, PA, Brazil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Biologia Molecular. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância em Saúde. Ananindeua, PA, Brasil.Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Laboratório de Biologia Molecular. Ananindeua, PA, Brasil / Ministério da Saúde. Secretaria de Vigilância em Saúde e Ambiente. Instituto Evandro Chagas. Programa de Pós-Graduação em Epidemiologia e Vigilância em Saúde. Ananindeua, PA, Brasil.Objectives: The horizontal transfer of antibiotic resistance genes in Gram-negative bacteria, mainly through plasmids, is one of the greatest concerns for health systems worldwide and has been a growing threat in hospitals related to healthcare-associated infections by multidrug-resistant bacteria. Here we present phenotypic and genomic characterization of a KPC-2 and MCR-1.27-producing Klebsiella pneumoniae strain isolated from a paediatric patient at an oncologic hospital in Belém, Pará State, Brazilian Amazon region. Methods: Antibiotic susceptibility test, whole genome sequencing, and in silico analysis were used to characterize the bacterial isolate (IEC48020) received in the Evandro Chagas Institute. Results: The isolate was resistant to carbapenems, colistin, polymyxin B, and several other antimicrobials and was susceptible in vitro just to tigecycline, classified as an extensively drug-resistant phenotype. Genomic analysis revealed IEC48020 strain belonged to sequence type 11, clonal complex 258 high-risk clone and the presence of eight plasmids, two of them harbouring mcr-1.27 and blaKPC-2 genes, and the presence of virulence-related genes encoding yersiniabactin, phospholipase D, and traT genes. Conclusions: The presence and dissemination of high-risk clone bacteria with high disseminating plasmids containing antibiotic resistance genes for last resource antibiotics treatment options is a threat to the healthcare system and demands efforts in surveillance and epidemiological research for better knowledge of the actual situation of antibiotic resistance in the healthcare system, especially in the Amazon region, Brazil

High efficiency application of a mate-paired library from next-generation sequencing to postlight sequencing: Corynebacterium pseudotuberculosis as a case study for microbial de novo genome assembly

Ramos RTJ, Carneiro AR, de Castro Soares S, et al. High efficiency application of a mate-paired library from next-generation sequencing to postlight sequencing: Corynebacterium pseudotuberculosis as a case study for microbial de novo genome assembly. Journal of microbiological methods. 2013;95(3):441-447.With the advent of high-throughput DNA sequencing platforms, there has been a reduction in the cost and time of sequencing. With these advantages, new challenges have emerged, such as the handling of large amounts of data, quality assessment, and the assembly of short reads. Currently, benchtop high-throughput sequencers enable the genomes of prokaryotic organisms to be sequenced within two hours with a reduction in coverage compared with the SOLiD, Illumina and 454 FLX Titanium platforms, making it necessary to evaluate the efficiency of less expensive benchtop instruments for prokaryotic genomics. In the present work, we evaluate and propose a methodology for the use of the Ion Torrent PGM platform for decoding the gram-positive bacterium Corynebacterium pseudotuberculosis, for which 15 complete genome sequences have already been deposited based on fragment and mate-paired libraries with a 3-kb insert size. Despite the low coverage, a single sequencing run using a mate-paired library generated 39 scaffolds after de novo assembly without data curation. This result is superior to that obtained by sequencing using libraries generated from fragments marketed by the equipment's manufacturer, as well as that observed for mate-pairs sequenced by SOLiD. The generated sequence added an extra 91kb to the genome available at NCBI