Model-based Analysis of ChIP-Seq (MACS)

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Abstract

MACS performs model-based analysis of ChIP-Seq data generated by short read sequencers.

Abstract

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 in the genome, allowing for more robust predictions. MACS compares favorably to existing ChIP-Seq peak-finding algorithms, and is freely available.

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Most cited references 13

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High-resolution profiling of histone methylations in the human genome.

Artem Barski, Suresh Cuddapah, Tae Hwan Roh … (2007)

Histone modifications are implicated in influencing gene expression. We have generated high-resolution maps for the genome-wide distribution of 20 histone lysine and arginine methylations as well as histone variant H2A.Z, RNA polymerase II, and the insulator binding protein CTCF across the human genome using the Solexa 1G sequencing technology. Typical patterns of histone methylations exhibited at promoters, insulators, enhancers, and transcribed regions are identified. The monomethylations of H3K27, H3K9, H4K20, H3K79, and H2BK5 are all linked to gene activation, whereas trimethylations of H3K27, H3K9, and H3K79 are linked to repression. H2A.Z associates with functional regulatory elements, and CTCF marks boundaries of histone methylation domains. Chromosome banding patterns are correlated with unique patterns of histone modifications. Chromosome breakpoints detected in T cell cancers frequently reside in chromatin regions associated with H3K4 methylations. Our data provide new insights into the function of histone methylation and chromatin organization in genome function.

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Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.

Pablo Tarazona-Álvarez, Rudolf Jaenisch, Aviva Aiden … (2007)

We report the application of single-molecule-based sequencing technology for high-throughput profiling of histone modifications in mammalian cells. By obtaining over four billion bases of sequence from chromatin immunoprecipitated DNA, we generated genome-wide chromatin-state maps of mouse embryonic stem cells, neural progenitor cells and embryonic fibroblasts. We find that lysine 4 and lysine 27 trimethylation effectively discriminates genes that are expressed, poised for expression, or stably repressed, and therefore reflect cell state and lineage potential. Lysine 36 trimethylation marks primary coding and non-coding transcripts, facilitating gene annotation. Trimethylation of lysine 9 and lysine 20 is detected at satellite, telomeric and active long-terminal repeats, and can spread into proximal unique sequences. Lysine 4 and lysine 9 trimethylation marks imprinting control regions. Finally, we show that chromatin state can be read in an allele-specific manner by using single nucleotide polymorphisms. This study provides a framework for the application of comprehensive chromatin profiling towards characterization of diverse mammalian cell populations.

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Global variation in copy number in the human genome.

Mandy H. Perry, Daisuke Komura, Fengtang Yang … (2006)

Copy number variation (CNV) of DNA sequences is functionally significant but has yet to be fully ascertained. We have constructed a first-generation CNV map of the human genome through the study of 270 individuals from four populations with ancestry in Europe, Africa or Asia (the HapMap collection). DNA from these individuals was screened for CNV using two complementary technologies: single-nucleotide polymorphism (SNP) genotyping arrays, and clone-based comparative genomic hybridization. A total of 1,447 copy number variable regions (CNVRs), which can encompass overlapping or adjacent gains or losses, covering 360 megabases (12% of the genome) were identified in these populations. These CNVRs contained hundreds of genes, disease loci, functional elements and segmental duplications. Notably, the CNVRs encompassed more nucleotide content per genome than SNPs, underscoring the importance of CNV in genetic diversity and evolution. The data obtained delineate linkage disequilibrium patterns for many CNVs, and reveal marked variation in copy number among populations. We also demonstrate the utility of this resource for genetic disease studies.

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Author and article information

Journal

Journal ID (nlm-ta): Genome Biol

Title: Genome Biology

Publisher: BioMed Central

ISSN (Print): 1465-6906

ISSN (Electronic): 1465-6914

Publication date (Print): 2008

Publication date (Electronic): 17 September 2008

Volume: 9

Issue: 9

Page: R137

Affiliations

[1 ]Department of Biostatistics and Computational Biology, Dana-Farber Cancer Institute and Harvard School of Public Health, 44 Binney Street, Boston, MA 02115, USA

[2 ]Division of Molecular and Cellular Oncology, Department of Medical Oncology, Dana-Farber Cancer Institute and Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 44 Binney Street, Boston, MA 02115, USA

[3 ]Gene Security Network, Inc., 2686 Middlefield Road, Redwood City, CA 94063, USA

[4 ]Molecular Pathology Unit and Center for Cancer Research, Massachusetts General Hospital and Department of Pathology, Harvard Medical School, 13th Street, Charlestown, MA 02129, USA

[5 ]Broad Institute of Harvard and MIT, 7 Cambridge Center, Cambridge, MA, 02142, USA

[6 ]Department of Genetics, Stanford University Medical Center, Stanford, CA 94305, USA

[7 ]Division of Biostatistics, Dan L Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA

Publisher ID: gb-2008-9-9-r137

DOI: 10.1186/gb-2008-9-9-r137

PMC ID: 2592715

PubMed ID: 18798982

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Model-based Analysis of ChIP-Seq (MACS)

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Most cited references 13

High-resolution profiling of histone methylations in the human genome.

Genome-wide maps of chromatin state in pluripotent and lineage-committed cells.

Global variation in copy number in the human genome.

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