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We present Model-based Analysis of ChIP-Seq data, MACS, which analyzes data generated by short read sequencers such as Solexa's Genome Analyzer. MACS empirically models the shift size of ChIP-Seq tags, and uses it to improve the spatial resolution of predicted binding sites. MACS also uses a dynamic Poisson distribution to effectively capture local biases(More)
We propose a fast and powerful analysis algorithm, titled Model-based Analysis of Tiling-arrays (MAT), to reliably detect regions enriched by transcription factor chromatin immunoprecipitation (ChIP) on Affymetrix tiling arrays (ChIP-chip). MAT models the baseline probe behavior by considering probe sequence and copy number on each array. It standardizes(More)
Estrogen plays an essential physiologic role in reproduction and a pathologic one in breast cancer. The completion of the human genome has allowed the identification of the expressed regions of protein-coding genes; however, little is known concerning the organization of their cis-regulatory elements. We have mapped the association of the estrogen receptor(More)
Complex organisms require tissue-specific transcriptional programs, yet little is known about how these are established. The transcription factor FoxA1 is thought to contribute to gene regulation through its ability to act as a pioneer factor binding to nucleosomal DNA. Through genome-wide positional analyses, we demonstrate that FoxA1 cell type-specific(More)
Chromatin plays a central role in eukaryotic gene regulation. We performed genome-wide mapping of epigenetically marked nucleosomes to determine their position both near transcription start sites and at distal regulatory elements, including enhancers. In prostate cancer cells, where androgen receptor binds primarily to enhancers, we found that androgen(More)
The evolution of prostate cancer from an androgen-dependent state to one that is androgen-independent marks its lethal progression. The androgen receptor (AR) is essential in both, though its function in androgen-independent cancers is poorly understood. We have defined the direct AR-dependent target genes in both androgen-dependent and -independent cancer(More)
MOTIVATION Transcription factors (TFs) regulate gene expression by recognizing and binding to specific regulatory regions on the genome, which in higher eukaryotes can occur far away from the regulated genes. Recently, Affymetrix developed the high-density oligonucleotide arrays that tile all the non-repetitive sequences of the human genome at 35 bp(More)
The MIT Faculty has made this article openly available. Please share how this access benefits you. Your story matters. permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. ChIP-Seq analysis <p>MACS performs model-based analysis of ChIP-Seq data generated by short read sequencers.</p> Abstract(More)
The increasing volume of ChIP-chip and ChIP-seq data being generated creates a challenge for standard, integrative and reproducible bioinformatics data analysis platforms. We developed a web-based application called Cistrome, based on the Galaxy open source framework. In addition to the standard Galaxy functions, Cistrome has 29 ChIP-chip- and(More)
Sequencing of DNase I hypersensitive sites (DNase-seq) is a powerful technique for identifying cis-regulatory elements across the genome. We studied the key experimental parameters to optimize performance of DNase-seq. Sequencing short fragments of 50-100 base pairs (bp) that accumulate in long internucleosome linker regions was more efficient for(More)