Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease

The work of this thesis has a common focus on bioinformatics, comparative genomics of fungal genomes and clinical genomics of human chronic disease. We primarily focused on using genomic data of dimorphic fungal pathogens in order to obtain a better perspective and understanding of how commonly used...

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Detalles Bibliográficos
Autor Principal: Gallo Bonilla, Juan Esteban
Otros Autores: Clay, Oliver
Formato: Tesis de doctorado (Doctoral Thesis)
Lenguaje:Español (Spanish)
Publicado: Universidad del Rosario 2017
Materias:
Acceso en línea:http://repository.urosario.edu.co/handle/10336/13803
id ir-10336-13803
recordtype dspace
institution EdocUR - Universidad del Rosario
collection DSpace
language Español (Spanish)
topic Genomics
Bioinformatics
Enfermedades
Genomics
Bioinformatics
Biología Computacional
Genoma fúngico
Genoma viral
Enfermedad crónica
spellingShingle Genomics
Bioinformatics
Enfermedades
Genomics
Bioinformatics
Biología Computacional
Genoma fúngico
Genoma viral
Enfermedad crónica
Gallo Bonilla, Juan Esteban
Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
description The work of this thesis has a common focus on bioinformatics, comparative genomics of fungal genomes and clinical genomics of human chronic disease. We primarily focused on using genomic data of dimorphic fungal pathogens in order to obtain a better perspective and understanding of how commonly used assembly, annotation and genomic comparison bioinformatics programs dealt with genomic data. Our group re-sequenced the reference strains that had been used for the existing assemblies and annotations of Paracoccidioides spp., and used the new, higher quality reads to substantially improve the reference assemblies and annotations of these pathogenic fungi. We also sequenced de novo the species Emmonsia crescens and E. parva, which are closely related to the causal agent of blastomycosis, Blastomyces dermatitidis, but non-pathogenic or with low virulence. We performed comparative analyses of gene content and structure between various strains of B. dermatitidis, E. crescens and E. parva. Using available sequences, we then designed and analytically validated two primer pairs from regions that are unique to Histoplasma capsulatum but present across diverse strains of this species, and can therefore be utilized to detect the presence of H. capsulatum. Using the same approach, we also designed and analytically validated three primer pairs of high confidence for the amplification of sequence fragments that are unique to the genus Paracoccidioides. We designed and implemented an algorithm that takes any given sequence(s) and splits the sequence into fragments in order to query the unique percentage of the fragment against a group of sequences that are closely related to the query as well as outgroups that may be relevant in clinical settings, including human. we genotyped 67 selected SNPs within the 9p21.3 locus of the human genome, motivated by its proven association with cardiovascular disease, for a Colombian cohort of 357 healthy individuals with data collected for detailed hemodynamic and other phenotypic traits. We also sequenced the exome of a patient with familiar hypercholesterolemia.
author2 Clay, Oliver
author_facet Clay, Oliver
Gallo Bonilla, Juan Esteban
format Tesis de doctorado (Doctoral Thesis)
author Gallo Bonilla, Juan Esteban
author_sort Gallo Bonilla, Juan Esteban
title Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
title_short Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
title_full Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
title_fullStr Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
title_full_unstemmed Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
title_sort next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease
publisher Universidad del Rosario
publishDate 2017
url http://repository.urosario.edu.co/handle/10336/13803
_version_ 1674171750736199680
spelling ir-10336-138032020-08-03T03:58:29Z Next-generation sequencing and genome analysis in dimorphic fungi and human: using genomic variation to recognize and understand disease Gallo Bonilla, Juan Esteban Clay, Oliver Genomics Bioinformatics Enfermedades Genomics Bioinformatics Biología Computacional Genoma fúngico Genoma viral Enfermedad crónica The work of this thesis has a common focus on bioinformatics, comparative genomics of fungal genomes and clinical genomics of human chronic disease. We primarily focused on using genomic data of dimorphic fungal pathogens in order to obtain a better perspective and understanding of how commonly used assembly, annotation and genomic comparison bioinformatics programs dealt with genomic data. Our group re-sequenced the reference strains that had been used for the existing assemblies and annotations of Paracoccidioides spp., and used the new, higher quality reads to substantially improve the reference assemblies and annotations of these pathogenic fungi. We also sequenced de novo the species Emmonsia crescens and E. parva, which are closely related to the causal agent of blastomycosis, Blastomyces dermatitidis, but non-pathogenic or with low virulence. We performed comparative analyses of gene content and structure between various strains of B. dermatitidis, E. crescens and E. parva. Using available sequences, we then designed and analytically validated two primer pairs from regions that are unique to Histoplasma capsulatum but present across diverse strains of this species, and can therefore be utilized to detect the presence of H. capsulatum. Using the same approach, we also designed and analytically validated three primer pairs of high confidence for the amplification of sequence fragments that are unique to the genus Paracoccidioides. We designed and implemented an algorithm that takes any given sequence(s) and splits the sequence into fragments in order to query the unique percentage of the fragment against a group of sequences that are closely related to the query as well as outgroups that may be relevant in clinical settings, including human. we genotyped 67 selected SNPs within the 9p21.3 locus of the human genome, motivated by its proven association with cardiovascular disease, for a Colombian cohort of 357 healthy individuals with data collected for detailed hemodynamic and other phenotypic traits. We also sequenced the exome of a patient with familiar hypercholesterolemia. The work of this thesis has a common focus on bioinformatics, comparative genomics of fungal genomes and clinical genomics of human chronic disease. We primarily focused on using genomic data of dimorphic fungal pathogens in order to obtain a better perspective and understanding of how commonly used assembly, annotation and genomic comparison bioinformatics programs dealt with genomic data. Our group re-sequenced the reference strains that had been used for the existing assemblies and annotations of Paracoccidioides spp., and used the new, higher quality reads to substantially improve the reference assemblies and annotations of these pathogenic fungi. We also sequenced de novo the species Emmonsia crescens and E. parva, which are closely related to the causal agent of blastomycosis, Blastomyces dermatitidis, but non-pathogenic or with low virulence. We performed comparative analyses of gene content and structure between various strains of B. dermatitidis, E. crescens and E. parva. Using available sequences, we then designed and analytically validated two primer pairs from regions that are unique to Histoplasma capsulatum but present across diverse strains of this species, and can therefore be utilized to detect the presence of H. capsulatum. Using the same approach, we also designed and analytically validated three primer pairs of high confidence for the amplification of sequence fragments that are unique to the genus Paracoccidioides. We designed and implemented an algorithm that takes any given sequence(s) and splits the sequence into fragments in order to query the unique percentage of the fragment against a group of sequences that are closely related to the query as well as outgroups that may be relevant in clinical settings, including human. we genotyped 67 selected SNPs within the 9p21.3 locus of the human genome, motivated by its proven association with cardiovascular disease, for a Colombian cohort of 357 healthy individuals with data collected for detailed hemodynamic and other phenotypic traits. We also sequenced the exome of a patient with familiar hypercholesterolemia. 2019-10-11 01:01:01: Script de automatizacion de embargos. info:eu-repo/date/embargoEnd/2019-10-10 2019-10-11 07:55:01: Script de automatizacion de embargos. 11 oct 2019 Le llego el correo automático de finalización de embargo. 11 oct 2019 Correo recibido, Por favor no abrir acceso a esta tesis ya que aun nos encontramos en proceso de publicación en revista científica de algunos de sus contenidos. Gracias Juan Esteban Gallo Scientific Director GenomaCES 11 oct 2019 se cambia el nombre del documento y se embarga nuevamente por dos años 2017-08-29 2017-10-10T12:32:35Z info:eu-repo/date/embargoEnd/2021-10-11 info:eu-repo/semantics/doctoralThesis info:eu-repo/semantics/acceptedVersion http://repository.urosario.edu.co/handle/10336/13803 spa http://creativecommons.org/licenses/by-nc-nd/2.5/co/ info:eu-repo/semantics/embargoedAccess application/pdf Universidad del Rosario Doctorado en Ciencias Biomédicas Facultad de Ciencias Naturales y Matemáticas instname:Universidad del Rosario reponame:Repositorio Institucional EdocUR Muñoz JF, Gallo JE, Misas E, McEwen JG, Clay OK. The eukaryotic genome, its reads, and the unfinished assembly. FEBS Lett. 2013 Jul 11;587(14):2090–3 Muñoz JF, Misas E, Gallo JE, McEwen JG, Clay OK. Limits to Sequencing and de novo Assembly: Classic Benchmark Sequences for Optimizing Fungal NGS Designs. In: Castillo LF, Cristancho M, Isaza G, Pinz n AS, Rodr guez JMC, editors. Advances in Computational Biology. Cham: Springer International Publishing; 2014. pp. 221–30. (Advances in Intelligent Systems and Computing; vol. 232). Gallo JE, Muñoz JF, Misas E, McEwen JG, Clay OK. The complex task of choosing a de novo assembly: lessons from fungal genomes. Comput Biol Chem. 2014 Dec;53 Pt A:97–107 Muñoz JF, Gauthier GM, Desjardins CA, Gallo JE, Holder J, Sullivan TD, et al. The Dynamic Genome and Transcriptome of the Human Fungal Pathogen Blastomyces and Close Relative Emmonsia. Haridas S, editor. PLoS Genet. 2015 Oct;11(10):e1005493 Misas E, Muñoz JF, Gallo JE, McEwen JG, Clay OK. From NGS assembly challenges to instability of fungal mitochondrial genomes: A case study in genome complexity. Comput Biol Chem. 2016 Apr;61:258–69. Muñoz JF, Farrer RA, Desjardins CA, Gallo JE, Sykes S, Sakthikumar S, et al. Genome Diversity, RecombinatLineages of Paracoccidioides. Mitchell AP, editor. mSphere. American Society for Microbiology Journals; 2016 Sep;1(5):e00213–6.ion, and Virulence across the Major Paynter NP, Chasman DI, Buring JE, Shiffman D, Cook NR, Ridker PM. Cardiovascular disease risk prediction with and without knowledge of genetic variation at chromosome 9p21.3. Ann Intern Med. NIH Public Access; 2009 Jan 20;150(2):65–72. Stefansson H, Ophoff RA, Steinberg S, Andreassen OA, Cichon S, Rujescu D, et al. Common variants conferring risk of schizophrenia. Nature. 2009 Aug 6;460(7256):744–7. Jarinova O, Stewart AFR, Roberts R, Wells G, Lau P, Naing T, et al. Functional analysis of the chromosome 9p21.3 coronary artery disease risk locus. Arterioscler Thromb Vasc Biol. American Heart Association, Inc; 2009 Oct;29(10):1671–7 Pasmant E, Sabbagh A, Vidaud M, Bièche I. ANRIL, a long, noncoding RNA, is an unexpected major hotspot in GWAS. FASEB J. Federation of American Societies for Experimental Biology; 2011 Feb;25(2):444–8. Scheffold T, Waldmüller S, Borisov K. A case of familial hypertrophic cardiomyopathy emphasizes the importance of parallel screening of multiple disease genes. Clin Res Cardiol. Springer-Verlag; 2011 Jul;100(7):627–8. Sherborne AL, Hosking FJ, Prasad RB, Kumar R, Koehler R, Vijayakrishnan J, et al. Variation in CDKN2A at 9p21.3 influences childhood acute lymphoblastic leukemia risk. Nat Genet. 2010 Jun;42(6):492–4. Lucioni M, Novara F, Fiandrino G, Riboni R, Fanoni D, Arra M, et al. Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion. Blood. American Society of Hematology; 2011 Oct 27;118(17):4591–4. Savola S, Nardi F, Scotlandi K, Picci P, Knuutila S. Microdeletions in 9p21.3 induce false negative results in CDKN2A FISH analysis of Ewing sarcoma. Cytogenet Genome Res. 2007;119(1-2):21–6 Silander K, Tang H, Myles S, Jakkula E, Timpson NJ, Cavalli-Sforza L, et al. Worldwide patterns of haplotype diversity at 9p21.3, a locus associated with type 2 diabetes and coronary heart disease. Genome Med. BioMed Central; 2009 May 12;1(5):51 Cheng X, Shi L, Nie S, Wang F, Li X, Xu C, et al. The same chromosome 9p21.3 locus is associated with type 2 diabetes and coronary artery disease in a Chinese Han population. Diabetes. 2011 Feb;60(2):680–4 Züchner S, Gilbert JR, Martin ER, Leon-Guerrero CR, Xu P-T, Browning C, et al. Linkage and association study of late-onset Alzheimer disease families linked to 9p21.3. Ann Hum Genet. Blackwell Publishing Ltd; 2008 Nov;72(Pt 6):725–31. Halaschek-Wiener J, Amirabbasi-Beik M, Monfared N, Pieczyk M, Sailer C, Kollar A, et al. Genetic variation in healthy oldest-old. Mary Bridger J, editor. PLoS ONE. 2009 Aug 14;4(8):e6641 Gallo JE. Current state of cardiovascular genomics in Colombia. Revista Colombiana de Cardiologia. 2017 Jan;24(1):e1–e2
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