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ChIP-on-chip significance analysis reveals large-scale binding and regulation by human transcription factor oncogenes Nature Precedings
Adam A. Margolin; Teresa Palomero; Pavel Sumazin; Andrea Califano; Adolfo Ferrando; Gustavo A. Stolovitzky.
ChIP-on-chip has emerged as a powerful tool to dissect the complex network of regulatory interactions between transcription factors and their targets. However, most ChIP-on-chip analysis methods use conservative approaches aimed to minimize false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Biochemically validated analysis in human T-cells reveals that three transcription factor oncogenes, NOTCH1, MYC, and HES1, bind one order of magnitude more promoters than previously thought. Gene expression profiling upon NOTCH1 inhibition shows broad-scale functional regulation across the entire range of predicted target genes, establishing a closer link between occupancy and...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Bioinformatics.
Ano: 2007 URL: http://precedings.nature.com/documents/1364/version/1
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Integrative Network-based Association Studies: Leveraging cell regulatory models in the post-GWAS era Nature Precedings
Andrea Califano; Atul Butte; Stephen Friend; Trey Ideker; Eric E. Schadt.
After completion of a number of large scale Genome-Wide Association Studies (GWAS), there is still a significant amount of trait and disease variance that cannot be explained by existing genetic variability. This review introduces new, Integrative Network-based Association Study (INAS) approaches that aim to minimize the impact from multiple hypothesis testing statistics, thus allowing the identification of rare variants/alterations and epistatic interactions. In particular we discuss methods that rely on the de novo computational, experimental, and integrative dissection of context specific molecular interaction networks (or interactomes, for short). We provide several examples of how these approaches may be used to tackle discovery of genetic variants...
Tipo: Manuscript Palavras-chave: Cancer; Genetics & Genomics; Molecular Cell Biology; Bioinformatics; Data Standards.
Ano: 2011 URL: http://precedings.nature.com/documents/5732/version/1
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