Array CGH data modeling and smoothing in Stationary Wavelet Packet Transform domain

Background

Array-based comparative genomic hybridization (array CGH) is a highly efficient technique, allowing the simultaneous measurement of genomic DNA copy number at hundreds or thousands of loci and the reliable detection of local one-copy-level variations. Characterization of these DNA copy number changes is important for both the basic understanding of cancer and its diagnosis. In order to develop effective methods to identify aberration regions from array CGH data, many recent research work focus on both smoothing-based and segmentation-based data processing. In this paper, we propose stationary packet wavelet transform based approach to smooth array CGH data. Our purpose is to remove CGH noise in whole frequency while keeping true signal by using bivariate model.

Results

In both synthetic and real CGH data, Stationary Wavelet Packet Transform (SWPT) is the best wavelet transform to analyze CGH signal in whole frequency. We also introduce a new bivariate shrinkage model which shows the relationship of CGH noisy coefficients of two scales in SWPT. Before smoothing, the symmetric extension is considered as a preprocessing step to save information at the border.

Conclusion

We have designed the SWTP and the SWPT-Bi which are using the stationary wavelet packet transform with the hard thresholding and the new bivariate shrinkage estimator respectively to smooth the array CGH data. We demonstrate the effectiveness of our approach through theoretical and experimental exploration of a set of array CGH data, including both synthetic data and real data. The comparison results show that our method outperforms the previous approaches.

     

Quantized correlation coefficient for measuring reproducibility of ChIP-chip data

Background  

Chromatin immunoprecipitation followed by microarray hybridization (ChIP-chip) is used to study protein-DNA interactions and histone modifications on a genome-scale. To ensure data quality, these experiments are usually performed in replicates, and a correlation coefficient between replicates is used often to assess reproducibility. However, the correlation coefficient can be misleading because it is affected not only by the reproducibility of the signal but also by the amount of binding signal present in the data.     

Normalization and experimental design for ChIP-chip data

Background  

Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been widely used to investigate the DNA binding sites for a variety of proteins on a genome-wide scale. However, several issues in the processing and analysis of ChIP-chip data have not been resolved fully, including the effect of background (mock control) subtraction and normalization within and across arrays.     

ChIPpeakAnno: a Bioconductor package to annotate ChIP-seq and ChIP-chip data

Background  

Chromatin immunoprecipitation (ChIP) followed by high-throughput sequencing (ChIP-seq) or ChIP followed by genome tiling array analysis (ChIP-chip) have become standard technologies for genome-wide identification of DNA-binding protein target sites. A number of algorithms have been developed in parallel that allow identification of binding sites from ChIP-seq or ChIP-chip datasets and subsequent visualization in the University of California Santa Cruz (UCSC) Genome Browser as custom annotation tracks. However, summarizing these tracks can be a daunting task, particularly if there are a large number of binding sites or the binding sites are distributed widely across the genome.     

Preferential binding of HIF-1 to transcriptionally active loci determines cell-type specific response to hypoxia

Background  

Hypoxia-inducible factor 1 (HIF-1) plays a key role in cellular adaptation to hypoxia. To better understand the determinants of HIF-1 binding and transactivation, we used ChIP-chip and gene expression profiling to define the relationship between the epigenetic landscape, sites of HIF-1 binding, and genes transactivated by hypoxia in two cell lines.     

Starr: Simple Tiling ARRay analysis of Affymetrix ChIP-chip data

Background  

Chromatin immunoprecipitation combined with DNA microarrays (ChIP-chip) is an assay used for investigating DNA-protein-binding or post-translational chromatin/histone modifications. As with all high-throughput technologies, it requires thorough bioinformatic processing of the data for which there is no standard yet. The primary goal is to reliably identify and localize genomic regions that bind a specific protein. Further investigation compares binding profiles of functionally related proteins, or binding profiles of the same proteins in different genetic backgrounds or experimental conditions. Ultimately, the goal is to gain a mechanistic understanding of the effects of DNA binding events on gene expression.     

A stepwise framework for the normalization of array CGH data

Background  

In two-channel competitive genomic hybridization microarray experiments, the ratio of the two fluorescent signal intensities at each spot on the microarray is commonly used to infer the relative amounts of the test and reference sample DNA levels. This ratio may be influenced by systematic measurement effects from non-biological sources that can introduce biases in the estimated ratios. These biases should be removed before drawing conclusions about the relative levels of DNA. The performance of existing gene expression microarray normalization strategies has not been evaluated for removing systematic biases encountered in array-based comparative genomic hybridization (CGH), which aims to detect single copy gains and losses typically in samples with heterogeneous cell populations resulting in only slight shifts in signal ratios. The purpose of this work is to establish a framework for correcting the systematic sources of variation in high density CGH array images, while maintaining the true biological variations.     

Strategies for analyzing highly enriched IP-chip datasets

Background  

Chromatin immunoprecipitation on tiling arrays (ChIP-chip) has been employed to examine features such as protein binding and histone modifications on a genome-wide scale in a variety of cell types. Array data from the latter studies typically have a high proportion of enriched probes whose signals vary considerably (due to heterogeneity in the cell population), and this makes their normalization and downstream analysis difficult.     

SeeGH – A software tool for visualization of whole genome array comparative genomic hybridization data

Background  

Array comparative genomic hybridization (CGH) is a technique which detects copy number differences in DNA segments. Complete sequencing of the human genome and the development of an array representing a tiling set of tens of thousands of DNA segments spanning the entire human genome has made high resolution copy number analysis throughout the genome possible. Since array CGH provides signal ratio for each DNA segment, visualization would require the reassembly of individual data points into chromosome profiles.