Abstract:
:DNA methylation plays key roles in diverse biological processes such as X chromosome inactivation, transposable element repression, genomic imprinting, and tissue-specific gene expression. Sequencing-based DNA methylation profiling provides an unprecedented opportunity to map and compare complete DNA methylomes. This includes one of the most widely applied technologies for measuring DNA methylation: methylated DNA immunoprecipitation followed by sequencing (MeDIP-seq), coupled with a complementary method, methylation-sensitive restriction enzyme sequencing (MRE-seq). A computational approach that integrates data from these two different but complementary assays and predicts methylation differences between samples has been unavailable. Here, we present a novel integrative statistical framework M&M (for integration of MeDIP-seq and MRE-seq) that dynamically scales, normalizes, and combines MeDIP-seq and MRE-seq data to detect differentially methylated regions. Using sample-matched whole-genome bisulfite sequencing (WGBS) as a gold standard, we demonstrate superior accuracy and reproducibility of M&M compared to existing analytical methods for MeDIP-seq data alone. M&M leverages the complementary nature of MeDIP-seq and MRE-seq data to allow rapid comparative analysis between whole methylomes at a fraction of the cost of WGBS. Comprehensive analysis of nineteen human DNA methylomes with M&M reveals distinct DNA methylation patterns among different tissue types, cell types, and individuals, potentially underscoring divergent epigenetic regulation at different scales of phenotypic diversity. We find that differential DNA methylation at enhancer elements, with concurrent changes in histone modifications and transcription factor binding, is common at the cell, tissue, and individual levels, whereas promoter methylation is more prominent in reinforcing fundamental tissue identities.
journal_name
Genome Resjournal_title
Genome researchauthors
Zhang B,Zhou Y,Lin N,Lowdon RF,Hong C,Nagarajan RP,Cheng JB,Li D,Stevens M,Lee HJ,Xing X,Zhou J,Sundaram V,Elliott G,Gu J,Shi T,Gascard P,Sigaroudinia M,Tlsty TD,Kadlecek T,Weiss A,O'Geen H,Farnham PJ,Mairedoi
10.1101/gr.156539.113subject
Has Abstractpub_date
2013-09-01 00:00:00pages
1522-40issue
9eissn
1088-9051issn
1549-5469pii
gr.156539.113journal_volume
23pub_type
杂志文章相关文献
GENOME RESEARCH文献大全abstract::Obtaining high-quality sequence continuity of complex regions of recent segmental duplication remains one of the major challenges of finishing genome assemblies. In the human and mouse genomes, this was achieved by targeting large-insert clones using costly and laborious capillary-based sequencing approaches. Sanger s...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.168450.113
更新日期:2014-04-01 00:00:00
abstract::CTCF is a ubiquitously expressed regulator of fundamental genomic processes including transcription, intra- and interchromosomal interactions, and chromatin structure. Because of its critical role in genome function, CTCF binding patterns have long been assumed to be largely invariant across different cellular environ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.136101.111
更新日期:2012-09-01 00:00:00
abstract::An important aspect of understanding a biological pathway is to delineate the transcriptional regulatory mechanisms of the genes involved. Two important tasks are often encountered when studying transcription regulation, i.e., (1) the identification of common transcriptional regulators of a set of coexpressed genes; (...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.4303406
更新日期:2006-03-01 00:00:00
abstract::The alignment of full-length human cDNA sequences to the finished sequence of the human genome provides a unique opportunity to study the distribution of genes throughout the genome. By analyzing the distances between 23,752 genes, we identified a class of divergently transcribed gene pairs, representing more than 10%...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.1982804
更新日期:2004-01-01 00:00:00
abstract::With the genomic sequencing of Arabidopsis nearing completion and rice sequencing very much in its infancy, a key question is whether we can exploit the Arabidopsis sequence to identify candidate genes for traits in cereal crops using a map-based approach. This requires the existence of colinearity between the Arabido...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.9.9.825
更新日期:1999-09-01 00:00:00
abstract::Transcription factors (TFs) are key mediators that propagate extracellular and intracellular signals through to changes in gene expression profiles. However, the rules by which promoters decode the amount of active TF into target gene expression are not well understood. To determine the mapping between promoter DNA se...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.212316.116
更新日期:2017-01-01 00:00:00
abstract::Next-generation sequencing technologies have made it possible to sequence targeted regions of the human genome in hundreds of individuals. Deep sequencing represents a powerful approach for the discovery of the complete spectrum of DNA sequence variants in functionally important genomic intervals. Current methods for ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.100040.109
更新日期:2010-04-01 00:00:00
abstract::Chromatin immunoprecipitation coupled with high-throughput sequencing (ChIP-seq) has become the dominant technique for mapping transcription factor (TF) binding regions genome-wide. We performed an integrative analysis centered around 457 ChIP-seq data sets on 119 human TFs generated by the ENCODE Consortium. We ident...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.139105.112
更新日期:2012-09-01 00:00:00
abstract::Integration of DNA viruses into the human genome plays an important role in various types of tumors, including hepatitis B virus (HBV)-related hepatocellular carcinoma. However, the molecular details and clinical impact of HBV integration on either human or HBV epigenomes are unknown. Here, we show that methylation of...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.175240.114
更新日期:2015-03-01 00:00:00
abstract::Cancer progression in humans is difficult to infer because we do not routinely sample patients at multiple stages of their disease. However, heterogeneous breast tumors provide a unique opportunity to study human tumor progression because they still contain evidence of early and intermediate subpopulations in the form...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.099622.109
更新日期:2010-01-01 00:00:00
abstract::Dictyostelium discoideum (DD), an extensively studied model organism for cell and developmental biology, belongs to the most derived group 4 of social amoebas, a clade of altruistic multicellular organisms. To understand genome evolution over long time periods and the genetic basis of social evolution, we sequenced th...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.121137.111
更新日期:2011-11-01 00:00:00
abstract::Mirtrons are intronic hairpin substrates of the dicing machinery that generate functional microRNAs. In this study, we describe experimental assays that defined the essential requirements for entry of introns into the mirtron pathway. These data informed a bioinformatic screen that effectively identified functional mi...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.113050.110
更新日期:2011-02-01 00:00:00
abstract::Extracellular cues play critical roles in the establishment of the epigenome during development and may also contribute to epigenetic perturbations found in disease states. The direct role of the local tissue environment on the post-development human epigenome, however, remains unclear due to limitations in studies of...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.166439.113
更新日期:2014-04-01 00:00:00
abstract::Centromeres pose an evolutionary paradox: strongly conserved in function but rapidly changing in sequence and structure. However, in the absence of damage, centromere locations are usually conserved within a species. We report here that isolates of the pathogenic yeast species Candida parapsilosis show within-species ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.257816.119
更新日期:2020-05-01 00:00:00
abstract::The most widely appreciated role of DNA is to encode protein, yet the exact portion of the human genome that is translated remains to be ascertained. We previously developed PhyloCSF, a widely used tool to identify evolutionary signatures of protein-coding regions using multispecies genome alignments. Here, we present...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.246462.118
更新日期:2019-12-01 00:00:00
abstract::Network "guilt by association" (GBA) is a proven approach for identifying novel disease genes based on the observation that similar mutational phenotypes arise from functionally related genes. In principle, this approach could account even for nonadditive genetic interactions, which underlie the synergistic combinatio...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.118992.110
更新日期:2011-07-01 00:00:00
abstract::The expression of most genes is regulated by multiple transcription factors. The interactions between transcription factors produce complex patterns of gene expression that are not always obvious from the arrangement of cis-regulatory elements in a promoter. One critical element of promoters is the TATA box, the docki...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.106732.110
更新日期:2010-10-01 00:00:00
abstract::Eukaryotic DNA replication initiates from multiple discrete sites in the genome, termed origins of replication (origins). Prior to S phase, multiple origins are poised to initiate replication by recruitment of the pre-replicative complex (pre-RC). For proper replication to occur, origin activation must be tightly regu...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.209940.116
更新日期:2017-02-01 00:00:00
abstract::Mammalian genomes contain many highly conserved nongenic sequences (CNGs) whose functional significance is poorly understood. Sets of CNGs have previously been identified by selecting the most conserved elements from a chromosome or genome, but in these highly selected samples, conservation may be unrelated to purifyi...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.3942005
更新日期:2005-10-01 00:00:00
abstract::We have developed a simplified method for multiplex PCR based on the use of chimeric primers. Each primer contains a 3' region complementary to sequence-specific recognition sites and a 5' region made up of an unrelated 20-nucleotide sequence. Identical reaction conditions, cycling times, and annealing temperatures ha...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.5.5.488
更新日期:1995-12-01 00:00:00
abstract::To effectively analyze the increasing amounts of available genomic data, improved comparative analytical tools that are accessible to and applicable by a broad scientific community are essential. We built the "2-n-way" software suite to provide a fundamental and innovative processing framework for revealing and compar...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.262261.120
更新日期:2020-10-01 00:00:00
abstract::Human genomic data of many types are readily available, but the complexity and scale of human molecular biology make it difficult to integrate this body of data, understand it from a systems level, and apply it to the study of specific pathways or genetic disorders. An investigator could best explore a particular prot...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.082214.108
更新日期:2009-06-01 00:00:00
abstract::Current generation DNA sequencing instruments are moving closer to seamlessly sequencing genomes of entire populations as a routine part of scientific investigation. However, while significant inroads have been made identifying small nucleotide variation and structural variations in DNA that impact phenotypes of inter...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.136739.111
更新日期:2013-01-01 00:00:00
abstract::Many missense substitutions are identified in single nucleotide polymorphism (SNP) data and large-scale random mutagenesis projects. Each amino acid substitution potentially affects protein function. We have constructed a tool that uses sequence homology to predict whether a substitution affects protein function. SIFT...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.176601
更新日期:2001-05-01 00:00:00
abstract::Despite the availability of dozens of animal genome sequences, two key questions remain unanswered: First, what fraction of any species' genome confers biological function, and second, are apparent differences in organismal complexity reflected in an objective measure of genomic complexity? Here, we address both quest...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.108795.110
更新日期:2010-10-01 00:00:00
abstract::Alternative splicing is a major mechanism for gene product regulation in many multicellular organisms. By using different exon combinations, some coding regions can encode amino acids in multiple reading frames in different transcripts. Here we performed a systematic search through a set of high-quality human transcri...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.4246506
更新日期:2006-02-01 00:00:00
abstract::WebLogo generates sequence logos, graphical representations of the patterns within a multiple sequence alignment. Sequence logos provide a richer and more precise description of sequence similarity than consensus sequences and can rapidly reveal significant features of the alignment otherwise difficult to perceive. Ea...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.849004
更新日期:2004-06-01 00:00:00
abstract::Fragile sites are gaps and breaks in metaphase chromosomes generated by specific culture conditions. Fragile site FRA3B is the most unstable site and is directly involved in the breakpoints of deletion and translocation in a wide spectrum of cancers. To learn about the general characteristics of common fragile sites, ...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.2304404
更新日期:2004-07-01 00:00:00
abstract::Mutational analysis of large genes with complex genomic structures plays an important role in medical genetics. Technical limitations associated with current mutation screening protocols have placed increased emphasis on the development of new technologies to simplify these procedures. High-density arrays of >90,000-o...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.8.12.1245
更新日期:1998-12-01 00:00:00
abstract::The Mouse Genome Sequencing Consortium and the RIKEN Genome Exploration Research grouphave generated large sets of sequence data representing the mouse genome and transcriptome, respectively. These data provide a valuable foundation for genomic research. The challenges for the informatics community are how to integrat...
journal_title:Genome research
pub_type: 杂志文章
doi:10.1101/gr.991003
更新日期:2003-06-01 00:00:00