Identification of SNP-containing regulatory motifs in the myelodysplastic syndromes model using SNP arrays and gene expression arrays / 癌症
Chinese Journal of Cancer
;
(12): 170-185, 2013.
Artículo
en Inglés
| WPRIM
| ID: wpr-295808
ABSTRACT
Myelodysplastic syndromes have increased in frequency and incidence in the American population, but patient prognosis has not significantly improved over the last decade. Such improvements could be realized if biomarkers for accurate diagnosis and prognostic stratification were successfully identified. In this study, we propose a method that associates two state-of-the-art array technologies--single nucleotide polymor-phism(SNP) array and gene expression array--with gene motifs considered transcription factor-binding sites (TFBS). We are particularly interested in SNP-containing motifs introduced by genetic variation and mutation as TFBS. The potential regulation of SNP-containing motifs affects only when certain mutations occur. These motifs can be identified from a group of co-expressed genes with copy number variation. Then, we used a sliding window to identify motif candidates near SNPs on gene sequences. The candidates were filtered by coarse thresholding and fine statistical testing. Using the regression-based LARS-EN algorithm and a level-wise sequence combination procedure, we identified 28 SNP-containing motifs as candidate TFBS. We confirmed 21 of the 28 motifs with ChIP-chip fragments in the TRANSFAC database. Another six motifs were validated by TRANSFAC via searching binding fragments on co-regulated genes. The identified motifs and their location genes can be considered potential biomarkers for myelodysplastic syndromes. Thus, our proposed method, a novel strategy for associating two data categories, is capable of integrating information from different sources to identify reliable candidate regulatory SNP-containing motifs introduced by genetic variation and mutation.
Texto completo:
Disponible
Índice:
WPRIM (Pacífico Occidental)
Asunto principal:
Factores de Transcripción
/
Sitios de Unión
/
Síndromes Mielodisplásicos
/
Algoritmos
/
Genes Reguladores
/
Análisis de Secuencia por Matrices de Oligonucleótidos
/
Perfilación de la Expresión Génica
/
Polimorfismo de Nucleótido Simple
/
Bases de Datos Genéticas
/
Variaciones en el Número de Copia de ADN
Tipo de estudio:
Estudio diagnóstico
/
Estudio pronóstico
Límite:
Humanos
Idioma:
Inglés
Revista:
Chinese Journal of Cancer
Año:
2013
Tipo del documento:
Artículo
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