huali's library 16 articles

Abstract

10.1101/gr.079558.108 Ultra-high-throughput sequencing is emerging as an attractive alternative to microarrays for genotyping, analysis of methylation patterns, and identification of transcription factor binding sites. Here, we describe an application of the Illumina sequencing (formerly Solexa sequencing) platform to study mRNA expression levels. Our goals were to estimate technical variance associated with Illumina sequencing in this context and to compare its ability to identify differentially expressed genes with existing array technologies. To do so, we estimated gene expression differences between liver and ...

Abstract

Recent papers have described the first application of high-throughput sequencing (HTS) technologies to the characterization of transcriptomes. These studies emphasize the tremendous power of this new technology, in terms of both profiling coverage and quantitative accuracy. Initial discoveries include the detection of substantial new transcript complexity, the elucidation of binding maps and regulatory properties of RNA-binding proteins, and new insights into the links between different steps in pre-mRNA processing. We review these findings, focusing on results from profiling mammalian transcriptomes. The ...

Abstract

Epigenetic research aims to understand heritable gene regulation that is not directly encoded in the DNA sequence. Epigenetic mechanisms such as DNA methylation and histone modifications modulate the packaging of the DNA in the nucleus and thereby influence gene expression. Patterns of epigenetic information are faithfully propagated over multiple cell divisions, which makes epigenetic regulation a key mechanism for cellular differentiation and cell fate decisions. In addition, incomplete erasure of epigenetic information can lead to complex patterns of non-Mendelian inheritance. Stochastic ...

Abstract

Chromatin immunoprecipitation (ChIP) followed by tag sequencing (ChIP-seq) using high-throughput next-generation instrumentation is fast, replacing chromatin immunoprecipitation followed by genome tiling array analysis (ChIP-chip) as the preferred approach for mapping of sites of transcription-factor binding and chromatin modification. Using two deeply sequenced data sets for human RNA polymerase II and STAT1, each with matching input-DNA controls, we describe a general scoring approach to address unique challenges in ChIP-seq data analysis. Our approach is based on the observation that sites of potential ...

Abstract

We present CisGenome, a software system for analyzing genome-wide chromatin immunoprecipitation (ChIP) data. CisGenome is designed to meet all basic needs of ChIP data analyses, including visualization, data normalization, peak detection, false discovery rate computation, gene-peak association, and sequence and motif analysis. In addition to implementing previously published ChIP-microarray (ChIP-chip) analysis methods, the software contains statistical methods designed specifically for ChlP sequencing (ChIP-seq) data obtained by coupling ChIP with massively parallel sequencing. The modular design of CisGenome enables it to support ...

Abstract

ChIP-chip (or ChIP-on-chip) is a technology for isolation and identification of genomic sites occupied by specific DNA-binding proteins in living cells. The ChIP-chip signals can be obtained over the whole genome by tiling arrays, where a peak shape is generally observed around a protein-binding site. In this article, we describe the ChIP-chip process and present a probability model for ChIP-chip data. We then propose a model-based method for recognizing the peak shapes for the purpose of detecting protein-binding sites. We also ...

Abstract

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 at minimizing false-positive transcription factor targets. We present a model with improved sensitivity in detecting binding events from ChIP-on-chip data. Its application to human T cells, followed by extensive biochemical validation, reveals that 3 oncogenic transcription factors, NOTCH1, MYC, and HES1, bind to several thousand target gene promoters, up to an ...

Abstract

MOTIVATION: Genes often regulate multiple traits. Identifying clusters of traits influenced by a common group of genes helps elucidate regulatory networks and can improve linkage mapping. METHODS: We show that the Pearson Correlation Coefficient, $$\stackrel∧ ρ _L$$, between two LOD score profiles can, with high specificity and sensitivity, identify pairs of genes that have their transcription regulated by shared QTL. Furthermore, using theoretical and/or empirical methods, we can approximate the distribution of $$\stackrel∧ ρ _L$$ under the null hypothesis of no ...

Abstract

We show that, in yeast, the divergence rate of gene expression is not correlated with that of its associated coding sequence. Gene essentiality influences both modes of evolution, but other properties related to protein structure or promoter composition are only correlated with coding-sequence divergence or gene expression divergence, respectively. Based on these findings, we discuss the possibilities of neutral evolution of gene expression and of different modes of evolution in unicellular versus multicellular organisms. ...

Abstract

Interacting or functionally related protein families tend to have similar phylogenetic trees. Based on this observation, techniques have been developed to predict interaction partners. The observed degree of similarity between the phylogenetic trees of two proteins is the result of many different factors besides the actual interaction or functional relationship between them. Such factors influence the performance of interaction predictions. One aspect that can influence this similarity is related to the fact that a given protein interacts with many others, and ...

Abstract

MOTIVATION: The evolution of viruses is very rapid and in addition to local point mutations (insertion, deletion, substitution) it also includes frequent recombinations, genome rearrangements and horizontal transfer of genetic materials (HGTS). Evolutionary analysis of viral sequences is therefore a complicated matter for two main reasons: First, due to HGTs and recombinations, the right model of evolution is a network and not a tree. Second, due to genome rearrangements, an alignment of the input sequences is not guaranteed. These facts encourage ...

Abstract

Pathway analysis of microarray data evaluates gene expression profiles of a priori defined biological pathways in association with a phenotype of interest. We propose a unified pathway-analysis method that can be used for diverse phenotypes including binary, multiclass, continuous, count, rate, and censored survival phenotypes. The proposed method also allows covariate adjustments and correlation in the phenotype variable that is encountered in longitudinal, cluster-sampled, and paired designs. These are accomplished by combining the regression-based test statistic for each individual gene in ...