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1.
J Cyst Fibros ; 22(4): 683-693, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37142522

RESUMO

BACKGROUND: A largely unexplored area of research is the identification and characterization of circular RNA (circRNA) in cystic fibrosis (CF). This study is the first to identify and characterize alterations in circRNA expression in cells lacking CFTR function. The circRNA expression profiles in whole blood transcriptomes from CF patients homozygous for the pathogenetic variant F508delCFTR are compared to healthy controls. METHODS: We developed a circRNA pipeline called circRNAFlow utilizing Nextflow. Whole blood transcriptomes from CF patients homozygous for the F508delCFTR-variant and healthy controls were utilized as input to circRNAFlow to discover dysregulated circRNA expression in CF samples compared to wild-type controls. Pathway enrichment analyzes were performed to investigate potential functions of dysregulated circRNAs in whole blood transcriptomes from CF samples compared to wild-type controls. RESULTS: A total of 118 dysregulated circRNAs were discovered in whole blood transcriptomes from CF patients homozygous for the F508delCFTR variant compared to healthy controls. 33 circRNAs were up regulated whilst 85 circRNAs were down regulated in CF samples compared to healthy controls. The overrepresented pathways of the host genes harboring dysregulated circRNA in CF samples compared to controls include positive regulation of responses to endoplasmic reticulum stress, intracellular transport, protein serine/threonine kinase activity, phospholipid-translocating ATPase complex, ferroptosis and cellular senescence. These enriched pathways corroborate the role of dysregulated cellular senescence in CF. CONCLUSION: This study highlights the underexplored roles of circRNAs in CF with a perspective to provide a more complete molecular characterization of CF.


Assuntos
Fibrose Cística , MicroRNAs , Humanos , RNA Circular/genética , RNA/genética , Transcriptoma , Fibrose Cística/genética , Senescência Celular , MicroRNAs/metabolismo
2.
BMC Bioinformatics ; 17(Suppl 13): 333, 2016 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-27766961

RESUMO

BACKGROUND: The genes that produce antibodies and the immune receptors expressed on lymphocytes are not germline encoded; rather, they are somatically generated in each developing lymphocyte by a process called V(D)J recombination, which assembles specific, independent gene segments into mature composite genes. The full set of composite genes in an individual at a single point in time is referred to as the immune repertoire. V(D)J recombination is the distinguishing feature of adaptive immunity and enables effective immune responses against an essentially infinite array of antigens. Characterization of immune repertoires is critical in both basic research and clinical contexts. Recent technological advances in repertoire profiling via high-throughput sequencing have resulted in an explosion of research activity in the field. This has been accompanied by a proliferation of software tools for analysis of repertoire sequencing data. Despite the widespread use of immune repertoire profiling and analysis software, there is currently no standardized format for output files from V(D)J analysis. Researchers utilize software such as IgBLAST and IMGT/High V-QUEST to perform V(D)J analysis and infer the structure of germline rearrangements. However, each of these software tools produces results in a different file format, and can annotate the same result using different labels. These differences make it challenging for users to perform additional downstream analyses. RESULTS: To help address this problem, we propose a standardized file format for representing V(D)J analysis results. The proposed format, VDJML, provides a common standardized format for different V(D)J analysis applications to facilitate downstream processing of the results in an application-agnostic manner. The VDJML file format specification is accompanied by a support library, written in C++ and Python, for reading and writing the VDJML file format. CONCLUSIONS: The VDJML suite will allow users to streamline their V(D)J analysis and facilitate the sharing of scientific knowledge within the community. The VDJML suite and documentation are available from https://vdjserver.org/vdjml/ . We welcome participation from the community in developing the file format standard, as well as code contributions.


Assuntos
Genômica/métodos , Receptores Imunológicos/genética , Software , Recombinação V(D)J , Humanos , Disseminação de Informação
3.
Gene ; 572(2): 191-7, 2015 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-26172868

RESUMO

BACKGROUND: We have previously demonstrated that cerebrospinal fluid-derived B cells from early relapsing-remitting multiple sclerosis (RRMS) patients that express a VH4 gene accumulate specific replacement mutations. These mutations can be quantified as a score that identifies such patients as having or likely to convert to RRMS. Furthermore, we showed that next generation sequencing is an efficient method for obtaining the sequencing information required by this mutation scoring tool, originally developed using the less clinically viable single-cell Sanger sequencing. OBJECTIVE: To determine the accuracy of MSPrecise, the diagnostic test that identifies the presence of the RRMS-enriched mutation pattern from patient cerebrospinal fluid B cells. METHODS: Cerebrospinal fluid cell pellets were obtained from RRMS and other neurological disease (OND) patient cohorts. VH4 gene segments were amplified, sequenced by next generation sequencing and analyzed for mutation score. RESULTS: The diagnostic test showed a sensitivity of 75% on the RRMS cohort and a specificity of 88% on the OND cohort. The accuracy of the test in identifying RRMS patients or patients that will develop RRMS is 84%. CONCLUSION: MSPrecise exhibits good performance in identifying patients with RRMS irrespective of time with RRMS.


Assuntos
Análise Mutacional de DNA/métodos , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Cadeias Pesadas de Imunoglobulinas/genética , Técnicas de Diagnóstico Molecular/métodos , Esclerose Múltipla Recidivante-Remitente/diagnóstico , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Família Multigênica , Esclerose Múltipla Recidivante-Remitente/líquido cefalorraquidiano , Esclerose Múltipla Recidivante-Remitente/genética , Sensibilidade e Especificidade , Adulto Jovem
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