A comprehensive genomic and transcriptomic analysis of dimorphic human pathogen fungi and its relation with virulence.

McEwen Ochoa, Juan Guillermo

Publication:
A comprehensive genomic and transcriptomic analysis of dimorphic human pathogen fungi and its relation with virulence.

dc.contributor.author	McEwen Ochoa, Juan Guillermo
dc.contributor.corporatename	Corporación para Investigaciones Biológicas (CIB) (Medellín, Colombia)	spa
dc.contributor.researchgroup	COL0000962 - Biología Celular y Molecular CIB/UdeA/U del Rosario, 1 - Fungal Genome sequencing and analyses, 2 - Escuela de Medicina y Ciencias de la salud, 3 - Facultad de Medicina
dc.coverage.projectdates	2015-2015	spa
dc.coverage.spatial	América del Norte
dc.coverage.spatial	América del Sur
dc.date.accessioned	2020-01-10T20:42:53Z
dc.date.accessioned	2020-12-18T01:02:00Z
dc.date.available	2020-01-10T20:42:53Z
dc.date.available	2020-12-18T01:02:00Z
dc.date.issued	2018
dc.description.abstract	The ascomycete order Onygenales includes most dimorphic fungi that are pathogenic to humans. The most virulent of these fungal pathogens are found in the genera Paracoccidioides, Histoplasma, Blastomyces (family Ajellomycetaceae) and Coccidioides, which all have special medical relevance for South and/or North America. Paracoccidioides brasiliensis is endemic in Latin America where it is the third leading cause of death from chronic infection in particular countries and Histoplasma capsulatum is endemic in the United States where it is the most common cause of fungal respiratory infections in healthy individuals. These organisms share a close evolutionary relationship and common strategies of pathogenesis. However, despite the high incidence of infection with thermally dimorphic fungi, there is little understood about the molecular virulence mechanisms utilized by these organisms to manipulate disease progression in the host. A central line of research on Paracoccidioides, Histoplasma and other dimorphic human pathogenic fungi at the genome and gene level is the identification and characterization of virulence factors or molecular traits that make this fungus pathogenic and could be used as a lead for the design of vaccines, drugs and diagnostic methods. Sequencing of genomes and transcriptomes and subsequent comparative analysis is a particularly straightforward way to exhaustively scan and characterize species or individual strains of interest for this purpose. We propose to approach these endemic pathogens from an advanced and previously tested comparative genomics and transcriptomics framework. Two very recent advances make this an opportune moment to fill the remaining knowledge gap in a systematic way. The first is that next-generation sequencing has become inexpensive, and now it is more attractive to sequence the genomes of multiple isolates (population DNAseq) or the transcriptomes of multiple conditions (RNAseq) both allowing comparative analysis. The second is that for the Ajellomycetaceae family there are now several references genomes of the dimorphic pathogens Paracoccidioides, Histoplasma and Blastomyces and also genomes from non or less pathogenic species from the same family comprising Emmonsia parva, E. crescens, E. pasteuriana, Spiromastix grisea and Polytolypa hystricis. Part of those genomes were assembled, annotated and analyzed by our group in collaboration with the Broad Institute in previous and current projects allowing us to obtain the know-how for genome-based studies. Both recent advances showed that is a perfect moment for our group to continue this avenue of comparative genomics and functional genomics on the dimorphic pathogenic fungi Paracoccidioides and Histoplasma, including strategies such as RNAseq and transcriptional profiling. Here we propose to sequence the genomes (DNAseq) of isolates with particular phenotypic and geographic location as well as transcriptomes (RNAseq) of reference strains of P. brasiliensis and H. capsulatum in a comparative population and functional genomics approach. By performing genome and transcriptome based studies we expected to achieve success in this multi-target project allowing us: 1) to update and to improve the reference genome assemblies and annotations of Paracoccidioides and Histoplasma; 2) to identify differential molecular traits and mechanisms related to the pathogenesis and virulence of H. capsulatum and P. brasiliensis via comparative genomics (gene gain/losses, family expansion/contractions, etc) with other closely related pathogens and non-pathogens of the Ajellomycetaceae family, and via population genomics analysis within isolates of the same species with particular interesting phenotypes, source or location (SNPs analysis, recombination analysis, selection analysis) and 3) to identify differentially transcribed genes between host simulated and non-host condition that could be related with fungal virulence and pathogenicity.	spa
dc.format.extent	16 páginas.	spa
dc.identifier.instname	Colciencias	spa
dc.identifier.reponame	Repositorio Colciencias	spa
dc.identifier.repourl	http://colciencias.metabiblioteca.com.co	spa
dc.identifier.uri	https://colciencias.metadirectorio.org/handle/11146/39837
dc.language.iso	eng	spa
dc.relation.ispartofseries	Informe;
dc.rights.accessrights	info:eu-repo/semantics/openAccess	spa
dc.rights.accessrights	http://purl.org/coar/access_right/c_abf2	spa
dc.rights.creativecommons	https://creativecommons.org/licenses/by/4.0/	spa
dc.subject.proposal	Comparative Genomics	spa
dc.subject.proposal	Dimorphic Pathogenic Fungi	spa
dc.subject.proposal	Transcriptomics	spa
dc.subject.proposal	Virulence and Pathogenicity	spa
dc.title	A comprehensive genomic and transcriptomic analysis of dimorphic human pathogen fungi and its relation with virulence.	spa
dc.type	Informe de investigación	spa
dc.type.coar	http://purl.org/coar/resource_type/c_18ws	spa
dc.type.content	Text	spa
dc.type.driver	info:eu-repo/semantics/report	spa
dc.type.redcol	https://purl.org/redcol/resource_type/PID	spa
dc.type.version	info:eu-repo/semantics/submittedVersion	spa
dc.type.version	http://purl.org/coar/version/c_71e4c1898caa6e32	spa
dc.type.version	info:eu-repo/semantics/submittedVersion	spa
dcterms.audience	Estudiantes, Profesores, Comunidad científica colombiana, etc.	spa
dspace.entity.type	Publication
oaire.awardnumber	221365842971	spa
oaire.funderidentifier.colciencias	100-2015
oaire.fundername	Departamento Administrativo de Ciencia, Tecnología e Innovación [CO] Colciencias	spa
oaire.fundingstream	Programa Nacional en Ciencias Básicas	spa
oaire.objetives	Provide high quality and high throughput transcriptomic data of selected strains of interest under contrasting conditions, relevant to thermal dimorphism, using Next Generation Sequencing and RNA sequencing (DNAse/RNAseq), and a comparative system implemented for this purpose. 2.Improve the existing reference genome assemblies at the Broad and the gene/protein sequences and their annotations, using the genomic and transcriptomic data obtained in the comparative system of Specific objective 1. 3.Using the data from the previous specific obkective, we plan to identify differential molecular traits and mechanisms relevant to the understanding of the pathogenesis and virulence of H. captulatum and P. brasiliensis via comparative genomics e.g., (gene gain/losses, family expansion/contractions) and population analysis (SNP analysis). 4.Use the transcriptome data in order to identify differential transcriptional profiles between conditions simulating host environments and non-host conditions that could be pertinent to virulence and pathogenicity, including transcriptional profiles based on messenger RNA molecules and also and less studied and understood molecules such as miRNA and non-coding RNAs. 5.Through the Broad Institute's web page, make publicly available, the system sequence data and metadata obtained and curated during the project. 6.Train and form personnel in state-of-the-art methods and research in fungal genomics and genome bioinformatics, and in this way contribute to raising the standard of this field in the country. "	spa