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Qian Qin, Shenglin Mei, Qiu Wu, Hanfei Sun, Lewyn Li, Len Taing, Sujun Chen, Fugen Li, Tao Liu, Chongzhi Zang, Han Xu, Yiwen Chen, Clifford A Meyer, Yong Zhang, Myles Brown, Henry W Long, X Shirley Liu
BACKGROUND: Transcription factor binding, histone modification, and chromatin accessibility studies are important approaches to understanding the biology of gene regulation. ChIP-seq and DNase-seq have become the standard techniques for studying protein-DNA interactions and chromatin accessibility respectively, and comprehensive quality control (QC) and analysis tools are critical to extracting the most value from these assay types. Although many analysis and QC tools have been reported, few combine ChIP-seq and DNase-seq data analysis and quality control in a unified framework with a comprehensive and unbiased reference of data quality metrics...
October 3, 2016: BMC Bioinformatics
Marco Masseroli, Abdulrahman Kaitoua, Pietro Pinoli, Stefano Ceri
While a huge amount of (epi)genomic data of multiple types is becoming available by using Next Generation Sequencing (NGS) technologies, the most important emerging problem is the so-called tertiary analysis, concerned with sense making, e.g., discovering how different (epi)genomic regions and their products interact and cooperate with each other. We propose a paradigm shift in tertiary analysis, based on the use of the Genomic Data Model (GDM), a simple data model which links genomic feature data to their associated experimental, biological and clinical metadata...
September 13, 2016: Methods: a Companion to Methods in Enzymology
Yuan Fang, Ximeng Wang, Lei Wang, Xiucai Pan, Jin Xiao, Xiu-E Wang, Yufeng Wu, Wenli Zhang
Bidirectional gene pairs tend to be highly coregulated and function in similar biological processes in eukaryotic genomes. Structural features and functional consequences of bidirectional promoters (BDPs) have received considerable attention among diverse species. However, the underlying mechanisms responsible for the bidirectional transcription and coexpression of BDPs remain poorly understood in plants. In this study, we integrated DNase-seq, RNA-seq, ChIP-seq and MNase-seq data and investigated the effect of physical DNase I hypersensitive site (DHS) positions on the transcription of rice BDPs...
2016: Scientific Reports
Su Wang, Chongzhi Zang, Tengfei Xiao, Jingyu Fan, Shenglin Mei, Qian Qin, Qiu Wu, Xujuan Li, Kexin Xu, Housheng Hansen He, Myles Brown, Clifford A Meyer, X Shirley Liu
Model-based analysis of regulation of gene expression (MARGE) is a framework for interpreting the relationship between the H3K27ac chromatin environment and differentially expressed gene sets. The framework has three main functions: MARGE-potential, MARGE-express, and MARGE-cistrome. MARGE-potential defines a regulatory potential (RP) for each gene as the sum of H3K27ac ChIP-seq signals weighted by a function of genomic distance from the transcription start site. The MARGE framework includes a compendium of RPs derived from 365 human and 267 mouse H3K27ac ChIP-seq data sets...
October 2016: Genome Research
Tatsunori Hashimoto, Richard I Sherwood, Daniel D Kang, Nisha Rajagopal, Amira A Barkal, Haoyang Zeng, Bart J M Emons, Sharanya Srinivasan, Tommi Jaakkola, David K Gifford
Enhancers and promoters commonly occur in accessible chromatin characterized by depleted nucleosome contact; however, it is unclear how chromatin accessibility is governed. We show that log-additive cis-acting DNA sequence features can predict chromatin accessibility at high spatial resolution. We develop a new type of high-dimensional machine learning model, the Synergistic Chromatin Model (SCM), which when trained with DNase-seq data for a cell type is capable of predicting expected read counts of genome-wide chromatin accessibility at every base from DNA sequence alone, with the highest accuracy at hypersensitive sites shared across cell types...
October 2016: Genome Research
Francesco Strino, Michael Lappe
BACKGROUND: Peak calling is a fundamental step in the analysis of data generated by ChIP-seq or similar techniques to acquire epigenetics information. Current peak callers are often hard to parameterise and may therefore be difficult to use for non-bioinformaticians. In this paper, we present the ChIP-seq analysis tool available in CLC Genomics Workbench and CLC Genomics Server (version 7.5 and up), a user-friendly peak-caller designed to be not specific to a particular *-seq protocol...
2016: BMC Bioinformatics
Isadore Budnick, Emily Hamburg-Shields, Demeng Chen, Eduardo Torre, Andrew Jarrell, Batool Akhtar-Zaidi, Olivia Cordovan, Rob C Spitale, Peter Scacheri, Radhika P Atit
Embryonic dermal fibroblasts in the skin have the exceptional ability to initiate hair follicle morphogenesis and contribute to scarless wound healing. Activation of the Wnt signaling pathway is critical for dermal fibroblast fate selection and hair follicle induction. In humans, mutations in Wnt pathway components and target genes lead to congenital focal dermal hypoplasias with diminished hair. The gene expression signature of embryonic dermal fibroblasts during differentiation and its dependence on Wnt signaling is unknown...
August 2016: Genesis: the Journal of Genetics and Development
David R Kelley, Jasper Snoek, John L Rinn
The complex language of eukaryotic gene expression remains incompletely understood. Despite the importance suggested by many noncoding variants statistically associated with human disease, nearly all such variants have unknown mechanisms. Here, we address this challenge using an approach based on a recent machine learning advance-deep convolutional neural networks (CNNs). We introduce the open source package Basset to apply CNNs to learn the functional activity of DNA sequences from genomics data. We trained Basset on a compendium of accessible genomic sites mapped in 164 cell types by DNase-seq, and demonstrate greater predictive accuracy than previous methods...
July 2016: Genome Research
Aleksander Jankowski, Jerzy Tiuryn, Shyam Prabhakar
MOTIVATION: Computational prediction of transcription factor (TF) binding sites in the genome remains a challenging task. Here, we present Romulus, a novel computational method for identifying individual TF binding sites from genome sequence information and cell-type-specific experimental data, such as DNase-seq. It combines the strengths of previous approaches, and improves robustness by reducing the number of free parameters in the model by an order of magnitude. RESULTS: We show that Romulus significantly outperforms existing methods across three sources of DNase-seq data, by assessing the performance of these tools against ChIP-seq profiles...
August 15, 2016: Bioinformatics
Yongqing Zhang, Xiaoyi Cao, Sheng Zhong
A set of new data types emerged from functional genomic assays, including ChIP-seq, DNase-seq, FAIRE-seq and others. The results are typically stored as genome-wide intensities (WIG/bigWig files) or functional genomic regions (peak/BED files). These data types present new challenges to big data science. Here, we present GeNemo, a web-based search engine for functional genomic data. GeNemo searches user-input data against online functional genomic datasets, including the entire collection of ENCODE and mouse ENCODE datasets...
July 8, 2016: Nucleic Acids Research
Christopher L Frank, Dinesh Manandhar, Raluca Gordân, Gregory E Crawford
BACKGROUND: Small molecule inhibitors of histone deacetylases (HDACi) hold promise as anticancer agents for particular malignancies. However, clinical use is often confounded by toxicity, perhaps due to indiscriminate hyperacetylation of cellular proteins. Therefore, elucidating the mechanisms by which HDACi trigger differentiation, cell cycle arrest, or apoptosis of cancer cells could inform development of more targeted therapies. We used the myelogenous leukemia line K562 as a model of HDACi-induced differentiation to investigate chromatin accessibility (DNase-seq) and expression (RNA-seq) changes associated with this process...
2016: Epigenetics & Chromatin
Leonardo M R Ferreira, Torsten B Meissner, Tarjei S Mikkelsen, William Mallard, Charles W O'Donnell, Tamara Tilburgs, Hannah A B Gomes, Raymond Camahort, Richard I Sherwood, David K Gifford, John L Rinn, Chad A Cowan, Jack L Strominger
HLA-G, a nonclassical HLA molecule uniquely expressed in the placenta, is a central component of fetus-induced immune tolerance during pregnancy. The tissue-specific expression of HLA-G, however, remains poorly understood. Here, systematic interrogation of the HLA-G locus using massively parallel reporter assay (MPRA) uncovered a previously unidentified cis-regulatory element 12 kb upstream of HLA-G with enhancer activity, Enhancer L Strikingly, clustered regularly-interspaced short palindromic repeats (CRISPR)/Cas9-mediated deletion of this enhancer resulted in ablation of HLA-G expression in JEG3 cells and in primary human trophoblasts isolated from placenta...
May 10, 2016: Proceedings of the National Academy of Sciences of the United States of America
Hirofumi Nakaoka, Aishwarya Gurumurthy, Takahide Hayano, Somayeh Ahmadloo, Waleed H Omer, Kosuke Yoshihara, Akihito Yamamoto, Keisuke Kurose, Takayuki Enomoto, Shigeo Akira, Kazuyoshi Hosomichi, Ituro Inoue
Genome-wide association studies (GWASs) have discovered numerous single nucleotide polymorphisms (SNPs) associated with human complex disorders. However, functional characterization of the disease-associated SNPs remains a formidable challenge. Here we explored regulatory mechanism of a SNP on chromosome 9p21 associated with endometriosis by leveraging "allele-specific" functional genomic approaches. By re-sequencing 1.29 Mb of 9p21 region and scrutinizing DNase-seq data from the ENCODE project, we prioritized rs17761446 as a candidate functional variant that was in perfect linkage disequilibrium with the original GWAS SNP (rs10965235) and located on DNase I hypersensitive site...
April 2016: PLoS Genetics
Vahid Jalili, Matteo Matteucci, Marco J Morelli, Marco Masseroli
Enriched region (ER) identification is a fundamental step in several next-generation sequencing (NGS) experiment types. Yet, although NGS experimental protocols recommend producing replicate samples for each evaluated condition and their consistency is usually assessed, typically pipelines for ER identification do not consider available NGS replicates. This may alter genome-wide descriptions of ERs, hinder significance of subsequent analyses on detected ERs and eventually preclude biological discoveries that evidence in replicate could support...
March 24, 2016: Briefings in Bioinformatics
Yuuki Imai
Next generation sequencer has strongly progress big data analyses in life science. Among various kinds of sequencing data sets, epigenetic platform has just been important key to clarify the questions on broad and detail phenomenon in various forms of life. In this report, it is introduced that the research on identification of novel transcription factors in osteoclastogenesis using DNase-seq. Big data on musculoskeletal research will be organized by IFMRS and is getting more crucial.
April 2016: Clinical Calcium
Shinya Nakamura, Sakae Tanaka
The importance of receptor activator of nuclear factor-κB ligand(RANKL)during osteoclastogenesis was discovered in 1998. After that Nfatc1, downstream gene of RANKL-RANK signaling, was identified as a master regulator of osteoclastogenesis by transcriptome analysis. In recent years, with the advancement of epigenetic analysis method and big data analysis technology, epigenetic analysis about osteoclastogenesis gradually progresses. Some papers using H3K4me3 and H3K27me3 histone modification change data, DNase-seq data and formaldehyde-assisted isolation of regulatory elements(FAIRE)-seq data during osteoclastogenesis were published recently...
April 2016: Clinical Calcium
Marco Antonio Mendoza-Parra, Mohamed-Ashick M Saleem, Matthias Blum, Pierre-Etienne Cholley, Hinrich Gronemeyer
The combination of massive parallel sequencing with a variety of modern DNA/RNA enrichment technologies provides means for interrogating functional protein-genome interactions (ChIP-seq), genome-wide transcriptional activity (RNA-seq; GRO-seq), chromatin accessibility (DNase-seq, FAIRE-seq, MNase-seq), and more recently the three-dimensional organization of chromatin (Hi-C, ChIA-PET). In systems biology-based approaches several of these readouts are generally cumulated with the aim of describing living systems through a reconstitution of the genome-regulatory functions...
2016: Methods in Molecular Biology
Songjoon Baek, Myong-Hee Sung
High-throughput sequencing technologies have made it possible for biologists to generate genome-wide profiles of chromatin features at the nucleotide resolution. Enzymes such as nucleases or transposes have been instrumental as a chromatin-probing agent due to their ability to target accessible chromatin for cleavage or insertion. On the scale of a few hundred base pairs, preferential action of the nuclear enzymes on accessible chromatin allows mapping of cell state-specific accessibility in vivo. Such accessible regions contain functionally important regulatory sites, including promoters and enhancers, which undergo active remodeling for cells adapting in a dynamic environment...
2016: Methods in Molecular Biology
Myong-Hee Sung, Songjoon Baek, Gordon L Hager
High-throughput sequencing technologies have allowed many gene locus-level molecular biology assays to become genome-wide profiling methods. DNA-cleaving enzymes such as DNase I have been used to probe accessible chromatin. The accessible regions contain functional regulatory sites, including promoters, insulators and enhancers. Deep sequencing of DNase-seq libraries and computational analysis of the cut profiles have been used to infer protein occupancy in the genome at the nucleotide level, a method introduced as 'digital genomic footprinting'...
March 2016: Nature Methods
Eduardo G Gusmao, Manuel Allhoff, Martin Zenke, Ivan G Costa
DNase-seq allows nucleotide-level identification of transcription factor binding sites on the basis of a computational search of footprint-like DNase I cleavage patterns on the DNA. Frequently in high-throughput methods, experimental artifacts such as DNase I cleavage bias affect the computational analysis of DNase-seq experiments. Here we performed a comprehensive and systematic study on the performance of computational footprinting methods. We evaluated ten footprinting methods in a panel of DNase-seq experiments for their ability to recover cell-specific transcription factor binding sites...
April 2016: Nature Methods
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