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Pesquisa : H01.158.273.180 [Categoria DeCS]
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Id: biblio-1177915
Autor: Gomes de Andrade, Carlos Alberto.
Título: Diseño de estrategias para controlar la resistencia a los antimicrobianos utilizando herramientas de bioinformática y modelado molecular / Design of strategies to control antimicrobial resistance using bioinformatics tools and molecular modeling.
Fonte: Caracas; s.n; dic, 2011. 239 p. tab, ilus, graf. (Ift4872011615729).
Idioma: es.
Tese: Apresentada a Universidad Central de Venezuela. Facultad de Farmacia para obtenção do grau de Doctor.
Símbolo: Ift4872011615729.
Resumo: El éxito del tratamiento de las enfermedades infecciosas se ha visto comprometido en los últimos años debido a la diseminación de genes de resistencia a antibióticos entre las bacterias patógenas. Estos genes de resistencia a antibióticos son transportados por plásmidos, los cuáles son transferidos de una bacteria a otra mediante el proceso de conjugación. La reducción del uso inadecuado de los antibióticos y la búsqueda de inhibidores de la conjugación bacteriana son estrategias que podrían contribuir a la solución de este grave problema de salud pública. Basándose en la primera de esta estrategias, en enero de 2006 se regulo la dispensación de un grupo de antibióticos a fin de controlar su consumo. El análisis realizado en este trabajo seǹala que esta medida ha resultado ineficaz, puesto que el consumo y la resistencia bacteriana total a estos antimicrobianos se incrementó significativamente durante el periodo posterior a su promulgación. La resistencia bacteriana a muchas de las familias de antibióticos estudiadas esta solo parcialmente influenciada por su consumo, destacando la participación de otros factores, como la transferencia de genes de resistencia a antibióticos, en la prevalencia de cepas bacterianas resistentes. La identificación de proteínas del cito-cromo P450 de estructura y ligados conocidos, que tenían una similitud significativa en su secuencia de aminoácidos con la proteína de acoplamiento TRAG de los plásmidos R27 y R478, permitió identificar a los medicamentos diclofenac y ketoprofeno como potenciales inhibidores de la transferencia por conjugación de estos plásmidos. El modelado por homología de TRAG revelo que su dominio de solo hélices alfa podría ser el blanco de estos medicamentos. El ingreso de diclofenac o ketoprofeno a una cavidad en este dominio podría interferir en la interacción con el DNA portador de genes de resistencia a antibióticos que esta siendo transferido mediante el proceso de conjugación.
Descritores: Resistência Microbiana a Medicamentos/genética
Anti-Inflamatórios não Esteroides/farmacologia
Conjugação Genética/efeitos dos fármacos
Biologia Computacional/métodos
Anti-Infecciosos/farmacologia
-Diclofenaco/uso terapêutico
Diclofenaco/farmacologia
Cetoprofeno/uso terapêutico
Cetoprofeno/farmacologia
Doenças Transmissíveis/tratamento farmacológico
Sequência de Aminoácidos/efeitos dos fármacos
Conformação Proteica em alfa-Hélice
Anti-Infecciosos/administração & dosagem
Anti-Infecciosos/efeitos adversos
Limites: Humanos
Tipo de Publ: Estudo de Avaliação
Responsável: VE497.1 - Biblioteca Dr. Oswaldo Enríquez Isava
VE497.1; D-CF, G65


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Id: biblio-1177447
Autor: Bai, Yu; Li, Wenliang; Xu, Guangyu; Cui, Guihua.
Título: A bioinformatics approach revealed the transcription factors of Helicobacter pylori pathogenic genes and their regulatory network nodes
Fonte: Electron. j. biotechnol;45:53-59, May 15, 2020. tab, ilus.
Idioma: en.
Projeto: Department of Education of Jilin Province; . Jilin Province Traditional Chinese Medicine Science and Technology Project; . Jilin Province Health and Family Planning Commission; . Jilin Science and Technology Innovation Development Plan Project.
Resumo: BACKGROUND: Helicobacter pylori is a chronic pathogenic bacteria that causes gastric mucosal damage through various host-related and pathogen-related factors. Thus, a single gene research cannot fully explain its pathogenicity. PURPOSE OF STUDY: It is necessary to establish a Helicobacter pylori pathogenic gene transcription factor regulatory network (TFRN) and study its central nodes. RESULTS: The expression data of Helicobacter pylori pathogenic genes were obtained through GEO Datasets of NCBI. The genes were screened using linear model-empirical Bayesian statistics in R language Limma package combined with the conventional t-test; the results identified 1231 differentially expressed genes. The functional analysis (gene ontology-analysis) and signal pathway analysis (pathway-analysis) of differentially expressed genes were performed using the DAVID and KEGG databases, respectively. The pathogenic gene regulatory network was constructed by integrating transcriptional regulatory element database (TRED); the disease-related analysis of the pathogenic genes was conducted using the DAVID annotation tool. Five pathogenic genes (Nos2, Il5, Colla1, Tnf, and Nfkb1) and their transcription factors (Jun, Cebpa, Egrl, Ppara, and Il6) were found to suppress the host immune function and enhance the pathogenicity of Helicobacter pylori by regulating the host immune system. CONCLUSIONS: This effect was largely mediated via three signaling pathways: Tnf pathway, PI3K Akt pathway, and Jak­STAT pathway. The pathogenicity of Helicobacter pylori is closely related to the body's immune and inflammatory system. A better understanding of the correlation of the pathogenic factors with the host immune and inflammatory factors may help to determine the precise pathogenic mechanism of H. pylori infection.
Descritores: Helicobacter pylori/genética
Helicobacter pylori/patogenicidade
Biologia Computacional
-Fatores de Transcrição
Citocinas
Fatores de Virulência
Gastrite/imunologia
Gastrite/microbiologia
Genes Bacterianos
Sistema Imunitário
Inflamação
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-1177412
Autor: Gupta, Verruchi; Singh, Inderpal; Rasool, Shafaq; Verma, Vijeshwar.
Título: Next generation sequencing and microbiome's taxonomical characterization of frozen soil of north western Himalayas of Jammu and Kashmir, India
Fonte: Electron. j. biotechnol;45:30-37, May 15, 2020. ilus, graf.
Idioma: es.
Projeto: Department of Biotechnology, Govt. of India.
Resumo: BACKGROUND: Traditionally, microbial genome sequencing has been restrained to the species grown in pure culture. The development of culture-independent techniques over the last decade allows scientists to sequence microbial communities directly from environmental samples. Metagenomics is the study of complex genome by the isolation of DNA of the whole community. Next generation sequencing (NGS) of metagenomic DNA gives information about the microbial and taxonomical characterization of a particular niche. The objective of the present research is to study the microbial and taxonomical characterization of the metagenomic DNA, isolated from the frozen soil sample of a glacier in the north western Himalayas through NGS. RESULTS: The glacier community comprised of 16 phyla with the representation of members belonging to Proteobacteria and Acidobacteria. The number of genes annotated through the Kyoto Encyclopedia of Genes and Genomes (KEGG), GO, Pfam, Clusters of Orthologous Groups of proteins (COGs), and FIG databases were generated by COGNIZER. The annotation of genes assigned in each group from the metagenomics data through COG database and the number of genes annotated in different pathways through KEGG database were reported. CONCLUSION: Results indicate that the glacier soil taken in the present study, harbors taxonomically and metabolically diverse communities. The major bacterial group present in the niche is Proteobacteria followed by Acidobacteria, and Actinobacteria, etc. Different genes were annotated through COG and KEGG databases that integrate genomic, chemical, and systemic functional information.
Descritores: Microbiologia do Solo
Bactérias/classificação
Sequenciamento de Nucleotídeos em Larga Escala
Microbiota/genética
-Bactérias/isolamento & purificação
Clima Frio
Biologia Computacional
Camada de Gelo
Metagenômica
Genoma Microbiano
Índia
Responsável: CL1.1 - Biblioteca Central


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Id: biblio-1254920
Autor: Nuñez, Suleivys M; Guzmán, Fanny; Valencia, Pedro; Almonacid, Sergio; Cárdenas, Constanza.
Título: Collagen as a source of bioactive peptides: a bioinformatics approach
Fonte: Electron. j. biotechnol;48:101-108, nov. 2020. tab, ilus.
Idioma: en.
Projeto: ANID PIA.
Resumo: BACKGROUND: Collagen is the most abundant protein in animals and can be obtained from residues of the food industry. Its hydrolysate has many desirable properties that make it suitable as an additive in foods and cosmetics, or as a component of scaffold materials to be used in biomedicine. RESULTS: We report here the characterization of type I collagen from five different sources, namely bovine, porcine, chicken, trout and salmon, as well as their hydrolysates by means of bioinformatics tools. As expected, the results showed that bovine and porcine collagen, as well as trout and salmon collagen, can be used interchangeably due to their high identity. This result is consistent with the evolution of proteins with highly identical sequences between related species. Also, 156 sequences were found as potential bioactive peptides, 126 from propeptide region and 30 from the central domain, according to the comparison with reported active sequences. CONCLUSIONS: Collagen analysis from a bioinformatic approach allowed us to classify collagen from 5 different animal sources, to establish its interchangeability as potential additive in diverse fields and also to determine the content of bioactive peptides from its in silico hydrolysis.
Descritores: Peptídeos
Colágeno/química
Biologia Computacional
-Hidrolisados de Proteína
Salmão
Suínos
Análise por Conglomerados
Colágeno Tipo I
Aditivos em Cosméticos
Aditivos Alimentares
Hidrólise
Limites: Animais
Bovinos
Responsável: CL1.1 - Biblioteca Central


  5 / 252 LILACS  
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Id: biblio-1254810
Autor: Wang, Sihu; Abbas Raza, Sayed Haidar; Mei, Chugang; Zhu, Kai; Garcia, Matthew; Schreurs, Nicola M; Liang, Chengcheng; Yang, Xinran; Zan, Linsen.
Título: Transcriptome profiling reveals differential expression of genes potentially involved in muscle and adipose tissue development of cattle
Fonte: Electron. j. biotechnol;48:72-77, nov. 2020. tab, ilus.
Idioma: en.
Projeto: National Key Research and Development Program of China; . National Natural Science Foundation of China; . National Key Technology Support Program; . National Beef and Yak Industrial Technology System; . Transformation Special Project of Scientific and Technological Achievements in Qinghai Province; . Agricultural Science and Technology Innovation and Transformation Project of Shaanxi Province.
Resumo: BACKGROUND: To identify differentially expressed genes (DEGs) between muscle and adipose in cattle, we analyzed the data from the RNA sequencing of three Angus×Qinchuan crossbred cattle. RESULTS: Searched the Gene Expression Omnibus (GEO) for a microarray dataset of Yan yellow cattle, GSE49992. After the DEGs were identified, we used STRING and Cytoscape to construct a protein­protein interaction (PPI) network, subsequently analyzing the major modules of key genes. In total, 340 DEGs were discovered, including 21 hub genes, which were mainly enriched in muscle contraction, skeletal muscle contraction, troponin complex, lipid particle, Z disc, tropomyosin binding, and actin filament binding. CONCLUSIONS: In summary, these genes can be regarded as candidate biomarkers for the regulation of muscle and adipose development.
Descritores: Tecido Adiposo/crescimento & desenvolvimento
Desenvolvimento Muscular/genética
Transcriptoma/genética
-Expressão Gênica
Regulação da Expressão Gênica no Desenvolvimento
Biologia Computacional
RNA-Seq
Limites: Animais
Bovinos
Responsável: CL1.1 - Biblioteca Central


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Texto completo SciELO Brasil
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Id: biblio-1279403
Autor: Estrada-Gómez, Sebastian; Vargas-Muñoz, Leidy Johana; Saldarriaga-Córdoba, Monica Maria; Meijden, Arie van der.
Título: MS/MS analysis of four scorpion venoms from Colombia: a descriptive approach
Fonte: J. venom. anim. toxins incl. trop. dis;27:e20200173, 2021. tab, graf.
Idioma: en.
Projeto: UdeA; . FEDER.
Resumo: Background: Scorpions are widely known for the neurotoxic effects of their venoms, which contain peptides affecting ionic channels. Although Colombia is recognized for its scorpion diversity, only a few studies are available describing the venom content. Methods: In this descriptive study, we analyzed the MS/MS sequence, electrophoretic and chromatographic profile linked to a bioinformatics analysis of the scorpions Chactas reticulatus (Chactidae), Opisthacanthus elatus (Hormuridae), Centruroides edwardsii (Buthidae) and Tityus asthenes (Buthidae) from Colombia. Results: Each scorpion showed a specific electrophoretic and chromatographic profile. The electrophoretic profiles indicate the presence of high molecular mass compounds in all venoms, with a predominance of low molecular mass compounds in the Buthidae species. Chromatographic profiles showed a similar pattern as the electrophoretic profiles. From the MS/MS analysis of the chromatographic collected fractions, we obtained internal peptide sequences corresponding to proteins reported in scorpions from the respective family of the analyzed samples. Some of these proteins correspond to neurotoxins affecting ionic channels, antimicrobial peptides and metalloproteinase-like fragments. In the venom of Tityus asthenes, the MSn analysis allowed the detection of two toxins affecting sodium channels covering 50% and 84% of the sequence respectively, showing 100% sequence similarity. Two sequences from Tityus asthenes showed sequence similarity with a phospholipase from Opisthacanthus cayaporum indicating the presence of this type of toxin in this species for the first time. One sequence matching a hypothetical secreted protein from Hottentotta judaicus was found in three of the studied venoms. We found that this protein is common in the Buthidae family whereas it has been reported in other families - such as Scorpionidae - and may be part of the evolutionary puzzle of venoms in these arachnids. Conclusion: Buthidae venoms from Colombia can be considered an important source of peptides similar to toxins affecting ionic channels. An interesting predicted antimicrobial peptide was detected in three of the analyzed venoms.(AU)
Descritores: Venenos de Escorpião
Sódio/análise
Biologia Computacional
Neurotoxinas
Limites: Animais
Responsável: BR68.1 - Biblioteca Virginie Buff D'Ápice


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Texto completo SciELO Cuba
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Id: lil-726997
Autor: Hernández Betancourt, Jenny de la Caridad; Serrano Barrera, Orlando.
Título: La medicina personalizada, la revolución genómica y el Sistema Nacional de Salud / Customized medicine, genomic revolution and the national health care system
Fonte: Rev. cuba. salud pública;40(4), oct.-dic. 2014.
Idioma: es.
Resumo: La profundización del conocimiento de los mecanismos moleculares del proceso salud-enfermedad ha hecho que avances científicos hayan encontrado lugar en la práctica clínica, como ha ocurrido en Cuba con las células madre. Los resultados derivados de la secuenciación del genoma humano y de otras especies mejora diagnósticos y tratamientos, sin embargo, dentro del sistema sanitario cubano no abundan las aplicaciones de las tecnologías genómicas. Esta nueva medicina necesita acumular todavía evidencia acerca de su seguridad y eficacia, se requiere una estrategia propia del Ministerio de Salud Pública en relación con la evaluación de sus usos, presentes y potenciales, en beneficio de la salud de la población. Se propone, entre otras acciones, constituir un grupo de trabajo multiinstitucional e intersectorial para estudiar las dimensiones clínicas, tecnológicas, reguladoras y bioéticas de la medicina genómica. Resulta imprescindible la preparación inmediata del personal que estudia en el pregrado o ya ejerce en las ciencias médicas, pues corresponderá a ellos la introducción y la extensión de estas tecnologías en el ejercicio de su práctica profesional. De manera inmediata es posible conformar cohortes que sean representativas de la población cubana, estudiarlas y conservar sus muestras en biobancos establecidos para tales fines. La progresiva introducción de las aplicaciones en la práctica clínica de la genómica y las tecnologías relacionadas, reclama del Sistema Nacional de Salud una atención que conduzca al estudio, la evaluación y propuesta de las acciones que permitan su implementación, según las evidencias y las condiciones y necesidades del modelo cubano de atención sanitaria(AU)

Deepening into the knowledge of the molecular mechanisms of the health/disease process has made many scientific advances to find a place into the clinical practice, as is the case of stem cells therapy in Cuba. The results derived from the sequencing of the human genome, as well of other species, have had an impact in the improvement of diagnoses and therapies; however, within the Cuban national health system the applications of genomic technologies are not widespread. Despite the fact that this new medicine still needs to accumulate much more evidence supporting its safety and efficacy, it is urgent to design a customized strategy by the Cuban Ministry of Public Health towards the assessment of current and potential uses of genomic medicine for the benefit of the population's health. Among other actions, this paper submitted the proposal of the creation of a multi-institutional and intersectoral taskforce to study the clinical, technological, regulatory and bioethical dimensions of genomic medicine. It is mandatory to train both undergraduate students and staff since they will be responsible to introduce and extend such technologies in their professional practice. It is already possible to make up cohorts resembling as much as possible the Cuban population, to study them and to collect and preserve their samples in biobanks established for such purposes(AU)
Descritores: Sistemas Nacionais de Saúde
Medicina Concierge/normas
Biologia Computacional
Genômica/métodos
-Cuba
Limites: Humanos
Masculino
Feminino
Responsável: CU1.1 - Biblioteca Médica Nacional


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Texto completo SciELO Cuba
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Id: lil-721273
Autor: Díaz Caballero, Antonio; Méndez Cuadro, Darío; Martínez Serrano, Emiliano; Orozco Páez, Jennifer; Velásquez, Margarita Rosa.
Título: Metaloproteinasas de la matriz en Odontología y sus consideraciones desde el campo de la química computacional / Matrix metalloproteinases and their considerations in Dentistry from the field of computational chemistry
Fonte: Rev. cuba. estomatol;51(1):80-92, ene.-mar. 2014.
Idioma: es.
Resumo: Las metaloproteinasas de la matriz son una familia de proteasas zinc-dependientes encargadas de la remodelación de los componentes proteicos de la matriz extracelular de todos los tejidos, su actividad catalítica es controlada por inhibidores tisulares de metaloproteinasas de la matriz. En condiciones patológicas se pierde el equilibrio existente entre MMPs con respecto a la de estos inhibidores endógenos, este desequilibrio es evidente en enfermedades orales como la caries dental, gingivitis, periodontitis, entre otras, por lo tanto la posibilidad de lograr una inhibición selectiva de la actividad de estas enzimas con inhibidores sintéticos constituye un enfoque prometedor en el tratamiento de distintas enfermedades de la cavidad oral. Se presenta a continuación una revisión bibliográfica cuyo objetivo es analizar el papel que juegan las metaloproteinasas de la matriz en el desarrollo de patologías orales e identificar el aporte que ha hecho el análisis computacional de estas enzimas en el campo de la odontología. Para tal fin se llevó a cabo una búsqueda de la literatura disponible en bases de datos como Pubmed, Sience Direct, Ovid y Ebsco Host empleando palabras claves como: patologías orales, cáncer oral, adhesión dentinaria, metaloproteinasas de la matriz, inhibidor sintético de metaloproteinasas y modelado molecular. Se seleccionaron 35 artículos para orientar la presente revisión. Al terminar se pudo concluir que existe correlación positiva entre la desregulación de determinadas MMPs y la progresión de ciertas enfermedades orales, esto ha impulsado la identificación y el diseño insílico de inhibidores efectivos para estas proteínas, partiendo de análisis relación estructura-actividad y acoplamiento molecular computacional. Hasta la fecha se ha logrado demostrar que los inhibidores de MMPs más potentes presentan grupos hidroxamatos. Teniendo en cuenta lo anterior, el diseño de compuestos que bloqueen la actividad representa una estrategia quimiopreventiva racional encaminada a la inhibición de las MMPs(AU)

Matrix metalloproteinases are a family of zinc-dependent proteases responsible for the remodeling the protein components of extracellular matrix of all tissues; its catalytic activity is controlled by tissue inhibitors of matrix metalloproteinases. At pathological conditions the balance between MMPs regarding these endogenous inhibitors is lost, this imbalance is evident in oral diseases including dental caries, gingivitis, periodontitis, among others, hence the possibility of achieving selective inhibition of activity of these enzymes with synthetic inhibitors is a promising approach in the treatment of various diseases of the oral cavity. A literature review aimed at analyzing the role of matrix metalloproteinases in the development of oral diseases and identify the contribution made by the computational analysis of these enzymes in the field of dentistry is presented below. To this end a search of the literature available was conducted in databases such as Pubmed, Sience Direct, Ovid, and Ebsco Host using keywords like: oral pathology, oral cancer, dentin bonding, matrix metalloproteinases, synthetic inhibitor of metalloproteinases, and molecular modeling. 35 items were selected to guide this review. At the end it was concluded that there is positive correlation between deregulation of certain MMPs and progression of certain oral diseases, this has boosted in silico identifying and designing effective inhibitors for these proteins, based on structure-activity relationship analysis and molecular docking computational. To date it has successfully demonstrated that the most potent inhibitors of MMPs have hydroxamate groups. So far it has successfully demonstrated that the most potent inhibitors of MMPs have hydroxamate groups. Considering the above, the design of compounds that block the chemopreventive activity represents a rational strategy for the inhibition of MMPs(AU)
Descritores: Biologia Computacional/métodos
Inibidores Teciduais de Metaloproteinases/metabolismo
Metaloproteinases da Matriz/fisiologia
-Literatura de Revisão como Assunto
Bases de Dados Bibliográficas
Limites: Humanos
Responsável: CU1.1 - Biblioteca Médica Nacional


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Texto completo SciELO Cuba
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Id: biblio-1251726
Autor: Molina Correo, Odiel Estrada; Fuentes Cancell, Dieter Reynaldo; Simón Grass, Willian; Álvarez Morales, Anaibis.
Título: Implementación del aula invertida en la carrera Ingeniería en Bioinformática: Estudio de caso / Implementation of the flipped classroom in the Engineering in Bioinformatics programs: Case study
Fonte: Rev. cuba. inform. méd;13(1):e389, ene.-jun. 2021. tab, graf.
Idioma: es.
Resumo: El presente trabajo aborda una experiencia en la implementación del aula invertida. Se emplea como estrategia de investigación un estudio de caso efectuado en la Universidad de las Ciencias Informáticas (UCI), de 16 estudiantes de Ingeniería en Bioinformática. En los resultados obtenidos, se confirma la relación entre la interactividad, motivación, trabajo y aprendizaje colaborativo y la evaluación formativa; además, que el diseño de actividades de aprendizaje y su evaluación en el modelo de aula invertida con el desarrollo de estrategias de estudiantes prosumidores de videos contribuye a que estos mejoren sus habilidades comunicativas e informáticas. Se concluye que la evaluación debe estimular el aprendizaje colaborativo, la interactividad, la tolerancia, la motivación y la responsabilidad en los entornos virtuales(AU)

This paper presents an experience in the flipped classroom teaching. A case study conducted at the University of Informatics Science (UCI, acronym in Spanish) with 16 Bioinformatics Engineering students. In the results obtained, the relationship between interactivity, motivation, work and collaborative learning and formative evaluation is confirmed; in addition, the design of learning activities and assessment in the flipped classroom model with the development of strategies for video prosumers students helps them to improve their communication and computer skills. It is concluded that evaluation should stimulate collaborative learning, interactivity, tolerance, motivation and responsibility in virtual environments(AU)
Descritores: Software
Biologia Computacional/métodos
Responsável: CU1.1 - Biblioteca Médica Nacional


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Texto completo SciELO Brasil
Mendonça, Berenice B
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Id: biblio-1153974
Autor: Montenegro, Luciana R; Lerário, Antônio M; Nishi, Miriam Y; Jorge, Alexander A L; Mendonca, Berenice B.
Título: Performance of mutation pathogenicity prediction tools on missense variants associated with 46, XY differences of sex development
Fonte: Clinics;76:e2052, 2021. tab, graf.
Idioma: en.
Projeto: Fapesp; . CNPq.
Resumo: OBJECTIVES: Single nucleotide variants (SNVs) are the most common type of genetic variation among humans. High-throughput sequencing methods have recently characterized millions of SNVs in several thousand individuals from various populations, most of which are benign polymorphisms. Identifying rare disease-causing SNVs remains challenging, and often requires functional in vitro studies. Prioritizing the most likely pathogenic SNVs is of utmost importance, and several computational methods have been developed for this purpose. However, these methods are based on different assumptions, and often produce discordant results. The aim of the present study was to evaluate the performance of 11 widely used pathogenicity prediction tools, which are freely available for identifying known pathogenic SNVs: Fathmn, Mutation Assessor, Protein Analysis Through Evolutionary Relationships (Phanter), Sorting Intolerant From Tolerant (SIFT), Mutation Taster, Polymorphism Phenotyping v2 (Polyphen-2), Align Grantham Variation Grantham Deviation (Align-GVGD), CAAD, Provean, SNPs&GO, and MutPred. METHODS: We analyzed 40 functionally proven pathogenic SNVs in four different genes associated with differences in sex development (DSD): 17β-hydroxysteroid dehydrogenase 3 (HSD17B3), steroidogenic factor 1 (NR5A1), androgen receptor (AR), and luteinizing hormone/chorionic gonadotropin receptor (LHCGR). To evaluate the false discovery rate of each tool, we analyzed 36 frequent (MAF>0.01) benign SNVs found in the same four DSD genes. The quality of the predictions was analyzed using six parameters: accuracy, precision, negative predictive value (NPV), sensitivity, specificity, and Matthews correlation coefficient (MCC). Overall performance was assessed using a receiver operating characteristic (ROC) curve. RESULTS: Our study found that none of the tools were 100% precise in identifying pathogenic SNVs. The highest specificity, precision, and accuracy were observed for Mutation Assessor, MutPred, SNP, and GO. They also presented the best statistical results based on the ROC curve statistical analysis. Of the 11 tools evaluated, 6 (Mutation Assessor, Phanter, SIFT, Mutation Taster, Polyphen-2, and CAAD) exhibited sensitivity >0.90, but they exhibited lower specificity (0.42-0.67). Performance, based on MCC, ranged from poor (Fathmn=0.04) to reasonably good (MutPred=0.66). CONCLUSION: Computational algorithms are important tools for SNV analysis, but their correlation with functional studies not consistent. In the present analysis, the best performing tools (based on accuracy, precision, and specificity) were Mutation Assessor, MutPred, and SNPs&GO, which presented the best concordance with functional studies.
Descritores: Biologia Computacional
Mutação de Sentido Incorreto/genética
-Virulência
Polimorfismo de Nucleotídeo Único
Desenvolvimento Sexual
Mutação
Limites: Humanos
Tipo de Publ: Research Support, Non-U.S. Gov't
Responsável: BR1.1 - BIREME



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