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In JoVE (1)

Other Publications (3)

Articles by Haipeng Xing in JoVE

 JoVE Biology

A Novel Bayesian Change-point Algorithm for Genome-wide Analysis of Diverse ChIPseq Data Types

1Department of Applied Mathematics & Statistics, Stony Brook University, 2Computational Biology and Bioinformatics, Cold Spring Harbor Laboratory, 3Department of Molecular and Cell Biology, University of Texas at Dallas


JoVE 4273

Our Bayesian Change Point (BCP) algorithm builds on state-of-the-art advances in modeling change-points via Hidden Markov Models and applies them to chromatin immunoprecipitation sequencing (ChIPseq) data analysis. BCP performs well in both broad and punctate data types, but excels in accurately identifying robust, reproducible islands of diffuse histone enrichment.

Other articles by Haipeng Xing on PubMed

Stochastic Segmentation Models for Array-based Comparative Genomic Hybridization Data Analysis

Array-based comparative genomic hybridization (array-CGH) is a high throughput, high resolution technique for studying the genetics of cancer. Analysis of array-CGH data typically involves estimation of the underlying chromosome copy numbers from the log fluorescence ratios and segmenting the chromosome into regions with the same copy number at each location. We propose for the analysis of array-CGH data, a new stochastic segmentation model and an associated estimation procedure that has attractive statistical and computational properties. An important benefit of this Bayesian segmentation model is that it yields explicit formulas for posterior means, which can be used to estimate the signal directly without performing segmentation. Other quantities relating to the posterior distribution that are useful for providing confidence assessments of any given segmentation can also be estimated by using our method. We propose an approximation method whose computation time is linear in sequence length which makes our method practically applicable to the new higher density arrays. Simulation studies and applications to real array-CGH data illustrate the advantages of the proposed approach.

Estimation of Parent Specific DNA Copy Number in Tumors Using High-density Genotyping Arrays

Chromosomal gains and losses comprise an important type of genetic change in tumors, and can now be assayed using microarray hybridization-based experiments. Most current statistical models for DNA copy number estimate total copy number, which do not distinguish between the underlying quantities of the two inherited chromosomes. This latter information, sometimes called parent specific copy number, is important for identifying allele-specific amplifications and deletions, for quantifying normal cell contamination, and for giving a more complete molecular portrait of the tumor. We propose a stochastic segmentation model for parent-specific DNA copy number in tumor samples, and give an estimation procedure that is computationally efficient and can be applied to data from the current high density genotyping platforms. The proposed method does not require matched normal samples, and can estimate the unknown genotypes simultaneously with the parent specific copy number. The new method is used to analyze 223 glioblastoma samples from the Cancer Genome Atlas (TCGA) project, giving a more comprehensive summary of the copy number events in these samples. Detailed case studies on these samples reveal the additional insights that can be gained from an allele-specific copy number analysis, such as the quantification of fractional gains and losses, the identification of copy neutral loss of heterozygosity, and the characterization of regions of simultaneous changes of both inherited chromosomes.

Genome-wide Localization of Protein-DNA Binding and Histone Modification by a Bayesian Change-point Method with ChIP-seq Data

Next-generation sequencing (NGS) technologies have matured considerably since their introduction and a focus has been placed on developing sophisticated analytical tools to deal with the amassing volumes of data. Chromatin immunoprecipitation sequencing (ChIP-seq), a major application of NGS, is a widely adopted technique for examining protein-DNA interactions and is commonly used to investigate epigenetic signatures of diffuse histone marks. These datasets have notoriously high variance and subtle levels of enrichment across large expanses, making them exceedingly difficult to define. Windows-based, heuristic models and finite-state hidden Markov models (HMMs) have been used with some success in analyzing ChIP-seq data but with lingering limitations. To improve the ability to detect broad regions of enrichment, we developed a stochastic Bayesian Change-Point (BCP) method, which addresses some of these unresolved issues. BCP makes use of recent advances in infinite-state HMMs by obtaining explicit formulas for posterior means of read densities. These posterior means can be used to categorize the genome into enriched and unenriched segments, as is customarily done, or examined for more detailed relationships since the underlying subpeaks are preserved rather than simplified into a binary classification. BCP performs a near exhaustive search of all possible change points between different posterior means at high-resolution to minimize the subjectivity of window sizes and is computationally efficient, due to a speed-up algorithm and the explicit formulas it employs. In the absence of a well-established "gold standard" for diffuse histone mark enrichment, we corroborated BCP's island detection accuracy and reproducibility using various forms of empirical evidence. We show that BCP is especially suited for analysis of diffuse histone ChIP-seq data but also effective in analyzing punctate transcription factor ChIP datasets, making it widely applicable for numerous experiment types.

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