Comparative study on ChIP-seq data: normalization and binding pattern characterization

Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive re...

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Published in:Bioinformatics Vol. 25; no. 18; pp. 2334 - 2340
Main Authors: Taslim, Cenny, Wu, Jiejun, Yan, Pearlly, Singer, Greg, Parvin, Jeffrey, Huang, Tim, Lin, Shili, Huang, Kun
Format: Journal Article
Language:English
Published: England Oxford University Press 15.09.2009
Oxford Publishing Limited (England)
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ISSN:1367-4803, 1367-4811, 1460-2059, 1367-4811
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Abstract Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-NormalK mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/ Contact: taslim.2@osu.edu; khuang@bmi.osu.edu Supplementary information: Supplementary data are available at Bioinformatics online.
AbstractList Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-NormalK mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/ Contact: taslim.2@osu.edu; khuang@bmi.osu.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal(K) mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/.
Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns.Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal super(K) mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples.Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII, Supplementary information: Supplementary data are available at Bioinformatics online.
Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns.MOTIVATIONAntibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns.We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal(K) mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples.RESULTSWe apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal(K) mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples.Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/.AVAILABILITYData are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/.
Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal K mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/ Contact: taslim.2@osu.edu; khuang@bmi.osu.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-NormalK mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/ Contact:  taslim.2@osu.edu; khuang@bmi.osu.edu Supplementary information:  Supplementary data are available at Bioinformatics online.
Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns.Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal(K) mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples.Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII, Supplementary information: Supplementary data are available at Bioinformatics online.
Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding patterns of specific protein molecules over the entire genome. ChIP-seq technology allows scientist to get more comprehensive results in shorter time. Here, we present a non-linear normalization algorithm and a mixture modeling method for comparing ChIP-seq data from multiple samples and characterizing genes based on their RNA polymerase II (Pol II) binding patterns. Results: We apply a two-step non-linear normalization method based on locally weighted regression (LOESS) approach to compare ChIP-seq data across multiple samples and model the difference using an Exponential-Normal[sup]K mixture model. Fitted model is used to identify genes associated with differential binding sites based on local false discovery rate (fdr). These genes are then standardized and hierarchically clustered to characterize their Pol II binding patterns. As a case study, we apply the analysis procedure comparing normal breast cancer (MCF7) to tamoxifen-resistant (OHT) cell line. We find enriched regions that are associated with cancer (P < 0.0001). Our findings also imply that there may be a dysregulation of cell cycle and gene expression control pathways in the tamoxifen-resistant cells. These results show that the non-linear normalization method can be used to analyze ChIP-seq data across multiple samples. Availability: Data are available at http://www.bmi.osu.edu/~khuang/Data/ChIP/RNAPII/ Contact: taslim.2@osu.edu; khuang@bmi.osu.edu Supplementary information: Supplementary data are available at Bioinformatics online.
Author Yan, Pearlly
Parvin, Jeffrey
Singer, Greg
Wu, Jiejun
Huang, Tim
Lin, Shili
Taslim, Cenny
Huang, Kun
AuthorAffiliation 1 Department of Molecular Virology, Immunology & Medical Genetics, 2 Department of Statistics, 3 Department of Biomedical Informatics and 4 OSUCCC Biomedical Informatics Shared Resources, The Ohio State University, Columbus, OH 43210, USA
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BackLink https://www.ncbi.nlm.nih.gov/pubmed/19561022$$D View this record in MEDLINE/PubMed
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Snippet Motivation: Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study...
Antibody-based Chromatin Immunoprecipitation assay followed by high-throughput sequencing technology (ChIP-seq) is a relatively new method to study the binding...
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SubjectTerms Binding Sites
Bioinformatics
Breast Neoplasms - metabolism
Cell Line, Tumor
Chromatin Immunoprecipitation - methods
Comparative studies
Computational Biology - methods
Female
Humans
Original Papers
RNA Polymerase II - metabolism
Sequence Analysis, DNA - methods
Title Comparative study on ChIP-seq data: normalization and binding pattern characterization
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