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https://www.readbyqxmd.com/read/28077088/integrated-rna-seq-and-dnase-seq-analyses-identify-phenotype-specific-bmp4-signaling-in-breast-cancer
#1
M Ampuja, T Rantapero, A Rodriguez-Martinez, M Palmroth, E L Alarmo, M Nykter, A Kallioniemi
BACKGROUND: Bone morphogenetic protein 4 (BMP4) plays an important role in cancer pathogenesis. In breast cancer, it reduces proliferation and increases migration in a cell line-dependent manner. To characterize the transcriptional mediators of these phenotypes, we performed RNA-seq and DNase-seq analyses after BMP4 treatment in MDA-MB-231 and T-47D breast cancer cells that respond to BMP4 with enhanced migration and decreased cell growth, respectively. RESULTS: The RNA-seq data revealed gene expression changes that were consistent with the in vitro phenotypes of the cell lines, particularly in MDA-MB-231, where migration-related processes were enriched...
January 11, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28011773/altre-workflow-for-defining-altered-regulatory-elements-using-chromatin-accessibility-data
#2
Elizabeth Baskin, Rick Farouni, Ewy A Mathé
: : Regulatory elements regulate gene transcription, and their location and accessibility is cell-type specific, particularly for enhancers. Mapping and comparing chromatin accessibility between different cell types may identify mechanisms involved in cellular development and disease progression. To streamline and simplify differential analysis of regulatory elements genome-wide using chromatin accessibility data, such as DNase-seq, ATAC-seq, we developed ALTRE (ALTered Regulatory Elements), an R package and associated R Shiny web app...
December 22, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27993786/defcom-analysis-and-modeling-of-transcription-factor-binding-sites-using-a-motif-centric-genomic-footprinter
#3
Bryan Quach, Terrence S Furey
MOTIVATION: Identifying the locations of transcription factor binding sites is critical for understanding how gene transcription is regulated across different cell types and conditions. Chromatin accessibility experiments such as DNaseI sequencing (DNase-seq) and Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) produce genome-wide data that include distinct "footprint" patterns at binding sites. Nearly all existing computational methods to detect footprints from these data assume that footprint signals are highly homogeneous across footprint sites...
December 19, 2016: Bioinformatics
https://www.readbyqxmd.com/read/27980060/quantifying-deleterious-effects-of-regulatory-variants
#4
Shan Li, Roberto Vera Alvarez, Roded Sharan, David Landsman, Ivan Ovcharenko
The majority of genome-wide association study (GWAS) risk variants reside in non-coding DNA sequences. Understanding how these sequence modifications lead to transcriptional alterations and cell-to-cell variability can help unraveling genotype-phenotype relationships. Here, we describe a computational method, dubbed CAPE, which calculates the likelihood of a genetic variant deactivating enhancers by disrupting the binding of transcription factors (TFs) in a given cellular context. CAPE learns sequence signatures associated with putative enhancers originating from large-scale sequencing experiments (such as ChIP-seq or DNase-seq) and models the change in enhancer signature upon a single nucleotide substitution...
December 15, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27903897/combining-atac-seq-with-nuclei-sorting-for-discovery-of-cis-regulatory-regions-in-plant-genomes
#5
Zefu Lu, Brigitte T Hofmeister, Christopher Vollmers, Rebecca M DuBois, Robert J Schmitz
: Chromatin structure plays a pivotal role in facilitating proper control of gene expression. Transcription factor (TF) binding of cis-elements is often associated with accessible chromatin regions. Therefore, the ability to identify these accessible regions throughout plant genomes will advance understanding of the relationship between TF binding, chromatin status and the regulation of gene expression. Assay for Transposase Accessible Chromatin sequencing (ATAC-seq) is a recently developed technique used to map open chromatin zones in animal genomes...
November 29, 2016: Nucleic Acids Research
https://www.readbyqxmd.com/read/27846892/choosing-panels-of-genomics-assays-using-submodular-optimization
#6
Kai Wei, Maxwell W Libbrecht, Jeffrey A Bilmes, William Stafford Noble
Due to the high cost of sequencing-based genomics assays such as ChIP-seq and DNase-seq, the epigenomic characterization of a cell type is typically carried out using a small panel of assay types. Deciding a priori which assays to perform is, thus, a critical step in many studies. We present the submodular selection of assays (SSA), a method for choosing a diverse panel of genomic assays that leverages methods from submodular optimization. More generally, this application serves as a model for how submodular optimization can be applied to other discrete problems in biology...
November 15, 2016: Genome Biology
https://www.readbyqxmd.com/read/27821050/stringent-comparative-sequence-analysis-reveals-sox10-as-a-putative-inhibitor-of-glial-cell-differentiation
#7
Chetna Gopinath, William D Law, José F Rodríguez-Molina, Arjun B Prasad, Lingyun Song, Gregory E Crawford, James C Mullikin, John Svaren, Anthony Antonellis
BACKGROUND: The transcription factor SOX10 is essential for all stages of Schwann cell development including myelination. SOX10 cooperates with other transcription factors to activate the expression of key myelin genes in Schwann cells and is therefore a context-dependent, pro-myelination transcription factor. As such, the identification of genes regulated by SOX10 will provide insight into Schwann cell biology and related diseases. While genome-wide studies have successfully revealed SOX10 target genes, these efforts mainly focused on myelinating stages of Schwann cell development...
November 7, 2016: BMC Genomics
https://www.readbyqxmd.com/read/27798116/most-brain-disease-associated-and-eqtl-haplotypes-are-not-located-within-transcription-factor-dnase-seq-footprints-in-brain
#8
Adam E Handel, Giuseppe Gallone, M Zameel Cader, Chris P Ponting
Dense genotyping approaches have revealed much about the genetic architecture both of gene expression and disease susceptibility. However, assigning causality to genetic variants associated with a transcriptomic or phenotypic trait presents a far greater challenge. The development of epigenomic resources by ENCODE, the Epigenomic Roadmap and others has led to strategies that seek to infer the likely functional variants underlying these genome-wide association signals. It is known, for example, that such variants tend to be located within areas of open chromatin, as detected by techniques such as DNase-seq and FAIRE-seq...
October 26, 2016: Human Molecular Genetics
https://www.readbyqxmd.com/read/27789702/cistrome-data-browser-a-data-portal-for-chip-seq-and-chromatin-accessibility-data-in-human-and-mouse
#9
Shenglin Mei, Qian Qin, Qiu Wu, Hanfei Sun, Rongbin Zheng, Chongzhi Zang, Muyuan Zhu, Jiaxin Wu, Xiaohui Shi, Len Taing, Tao Liu, Myles Brown, Clifford A Meyer, X Shirley Liu
Chromatin immunoprecipitation, DNase I hypersensitivity and transposase-accessibility assays combined with high-throughput sequencing enable the genome-wide study of chromatin dynamics, transcription factor binding and gene regulation. Although rapidly accumulating publicly available ChIP-seq, DNase-seq and ATAC-seq data are a valuable resource for the systematic investigation of gene regulation processes, a lack of standardized curation, quality control and analysis procedures have hindered extensive reuse of these data...
January 4, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/27716038/chilin-a-comprehensive-chip-seq-and-dnase-seq-quality-control-and-analysis-pipeline
#10
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
https://www.readbyqxmd.com/read/27637471/modeling-and-interoperability-of-heterogeneous-genomic-big-data-for-integrative-processing-and-querying
#11
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...
December 1, 2016: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/27558448/functional-characterization-of-open-chromatin-in-bidirectional-promoters-of-rice
#12
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...
August 25, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27466232/modeling-cis-regulation-with-a-compendium-of-genome-wide-histone-h3k27ac-profiles
#13
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
https://www.readbyqxmd.com/read/27456004/a-synergistic-dna-logic-predicts-genome-wide-chromatin-accessibility
#14
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
https://www.readbyqxmd.com/read/27295177/identifying-peaks-in-seq-data-using-shape-information
#15
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
https://www.readbyqxmd.com/read/27265328/defining-the-identity-of-mouse-embryonic-dermal-fibroblasts
#16
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
https://www.readbyqxmd.com/read/27197224/basset-learning-the-regulatory-code-of-the-accessible-genome-with-deep-convolutional-neural-networks
#17
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
https://www.readbyqxmd.com/read/27153645/romulus-robust-multi-state-identification-of-transcription-factor-binding-sites-from-dnase-seq-data
#18
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
https://www.readbyqxmd.com/read/27098038/genemo-a-search-engine-for-web-based-functional-genomic-data
#19
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
https://www.readbyqxmd.com/read/27087856/hdac-inhibitors-cause-site-specific-chromatin-remodeling-at-pu-1-bound-enhancers-in-k562-cells
#20
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
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