Enrichment for H3K27ac peaks
The figure displays the enrichment fold of identified regions for H3K27ac peaks in different tissues.download figure data
|E004||H1 BMP4 Derived Mesendoderm Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E005||H1 BMP4 Derived Trophoblast Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E006||H1 Derived Mesenchymal Stem Cells||ESC_DERIVED_PrimaryCulture|
|E007||H1 Derived Neuronal Progenitor Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E009||H9 Derived Neuronal Progenitor Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E010||H9 Derived Neuron Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E011||hESC Derived CD184+ Endoderm Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E012||hESC Derived CD56+ Ectoderm Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E013||hESC Derived CD56+ Mesoderm Cultured Cells||ESC_DERIVED_PrimaryCulture|
|E017||IMR90 fetal lung fibroblasts Cell Line||LUNG_CellLine|
|E021||iPS DF 6.9 Cells||IPSC_PrimaryCulture|
|E022||iPS DF 19.11 Cells||IPSC_PrimaryCulture|
|E023||Mesenchymal Stem Cell Derived Adipocyte Cultured Cells||FAT_PrimaryCulture|
|E025||Adipose Derived Mesenchymal Stem Cell Cultured Cells||FAT_PrimaryCulture|
|E026||Bone Marrow Derived Cultured Mesenchymal Stem Cells||STROMAL_CONNECTIVE_PrimaryCulture|
|E027||Breast Myoepithelial Primary Cells||BREAST_Adult|
|E028||Breast variant Human Mammary Epithelial Cells (vHMEC)||BREAST_PrimaryCulture|
|E029||Primary monocytes from peripheral blood||BLOOD_Adult|
|E030||Primary neutrophils from peripheral blood||BLOOD_Adult|
|E031||Primary B cells from cord blood||Blood_Fetal|
|E032||Primary B cells from peripheral blood||BLOOD_Adult|
|E033||Primary T cells from cord blood||Blood_Fetal|
|E034||Primary T cells from peripheral blood||BLOOD_Adult|
|E035||Primary hematopoietic stem cells||BLOOD_Adult|
|E036||Primary hematopoietic stem cells short term culture||BLOOD_Adult|
|E037||Primary T helper memory cells from peripheral blood 2||BLOOD_Adult|
|E038||Primary T helper naive cells from peripheral blood||BLOOD_Adult|
|E039||Primary T helper naive cells from peripheral blood||BLOOD_Adult|
|E040||Primary T helper memory cells from peripheral blood 1||BLOOD_Adult|
|E041||Primary T helper cells PMA-I stimulated||BLOOD_Adult|
|E042||Primary T helper 17 cells PMA-I stimulated||BLOOD_Adult|
|E043||Primary T helper cells from peripheral blood||BLOOD_Adult|
|E044||Primary T regulatory cells from peripheral blood||BLOOD_Adult|
|E045||Primary T cells effector/memory enriched from peripheral blood||BLOOD_Adult|
|E046||Primary Natural Killer cells from peripheral blood||BLOOD_Adult|
|E047||Primary T CD8+ naive cells from peripheral blood||BLOOD_Adult|
|E048||Primary T CD8+ memory cells from peripheral blood||BLOOD_Adult|
|E049||Mesenchymal Stem Cell Derived Chondrocyte Cultured Cells||STROMAL_CONNECTIVE_PrimaryCulture|
|E050||Primary hematopoietic stem cells G-CSF-mobilized Female||BLOOD_Adult|
|E051||Primary hematopoietic stem cells G-CSF-mobilized Male||BLOOD_Adult|
|E052||Muscle Satellite Cultured Cells||MUSCLE_PrimaryCulture|
|E053||Cortex derived primary cultured neurospheres||BRAIN_PrimaryCulture|
|E054||Ganglion Eminence derived primary cultured neurospheres||BRAIN_PrimaryCulture|
|E055||Foreskin Fibroblast Primary Cells skin01||SKIN_PrimaryCulture|
|E056||Foreskin Fibroblast Primary Cells skin02||SKIN_PrimaryCulture|
|E057||Foreskin Keratinocyte Primary Cells skin02||SKIN_PrimaryCulture|
|E058||Foreskin Keratinocyte Primary Cells skin03||SKIN_PrimaryCulture|
|E059||Foreskin Melanocyte Primary Cells skin01||SKIN_PrimaryCulture|
|E061||Foreskin Melanocyte Primary Cells skin03||SKIN_PrimaryCulture|
|E062||Primary mononuclear cells from peripheral blood||BLOOD_Adult|
|E067||Brain Angular Gyrus||BRAIN_Adult|
|E068||Brain Anterior Caudate||BRAIN_Adult|
|E069||Brain Cingulate Gyrus||BRAIN_Adult|
|E070||Brain Germinal Matrix||BRAIN_Fetal|
|E071||Brain Hippocampus Middle||BRAIN_Adult|
|E072||Brain Inferior Temporal Lobe||BRAIN_Adult|
|E074||Brain Substantia Nigra||BRAIN_Adult|
|E076||Colon Smooth Muscle||GI_COLON_Adult|
|E078||Duodenum Smooth Muscle||GI_DUODENUM_Adult|
|E080||Fetal Adrenal Gland||ADRENAL_Fetal|
|E081||Fetal Brain Male||BRAIN_Fetal|
|E082||Fetal Brain Female||BRAIN_Fetal|
|E084||Fetal Intestine Large||GI_INTESTINE_Fetal|
|E085||Fetal Intestine Small||GI_INTESTINE_Fetal|
|E089||Fetal Muscle Trunk||MUSCLE_Fetal|
|E090||Fetal Muscle Leg||MUSCLE_Fetal|
|E101||Rectal Mucosa Donor 29||GI_RECTUM_Adult|
|E102||Rectal Mucosa Donor 31||GI_RECTUM_Adult|
|E103||Rectal Smooth Muscle||GI_RECTUM_Adult|
|E107||Skeletal Muscle Male||MUSCLE_Adult|
|E108||Skeletal Muscle Female||MUSCLE_Adult|
|E111||Stomach Smooth Muscle||GI_STOMACH_Adult|
|E114||A549 EtOH 0.02pct Lung Carcinoma Cell Line||LUNG_CellLine|
|E115||Dnd41 TCell Leukemia Cell Line||BLOOD_CellLine|
|E116||GM12878 Lymphoblastoid Cells||BLOOD_PrimaryCulture|
|E117||HeLa-S3 Cervical Carcinoma Cell Line||CERVIX_CellLine|
|E118||HepG2 Hepatocellular Carcinoma Cell Line||LIVER_CellLine|
|E119||HMEC Mammary Epithelial Primary Cells||BREAST_PrimaryCulture|
|E120||HSMM Skeletal Muscle Myoblasts Cells||MUSCLE_PrimaryCulture|
|E121||HSMM cell derived Skeletal Muscle Myotubes Cells||MUSCLE_PrimaryCulture|
|E122||HUVEC Umbilical Vein Endothelial Primary Cells||VASCULAR_PrimaryCulture|
|E123||K562 Leukemia Cells||BLOOD_PrimaryCulture|
|E124||Monocytes-CD14+ RO01746 Primary Cells||BLOOD_Adult|
|E125||NH-A Astrocytes Primary Cells||BRAIN_PrimaryCulture|
|E126||NHDF-Ad Adult Dermal Fibroblast Primary Cells||SKIN_PrimaryCulture|
|E127||NHEK-Epidermal Keratinocyte Primary Cells||SKIN_PrimaryCulture|
|E128||NHLF Lung Fibroblast Primary Cells||LUNG_PrimaryCulture|
|E129||Osteoblast Primary Cells||BONE_PrimaryCulture|
Tissue enrichment index for H3K27ac
The figure plots the tissue enrichment index CTM distribution based on H3K27ac expression for identified regions in different tissues.download figure data
The Human Reference Epigenome Map, generated by the Roadmap Epigenomics Consortium, contains thousands of genome-wide epigenomic datasets that describe epigenomes of a variety of different human tissue and cell types. This map has allowed investigators to obtain a much deeper and more comprehensive view of our regulatory genome, for example defining regulatory elements including all promoters and enhancers for a given tissue or cell type. An outstanding task is to combine and compare different epigenomes in order to identify regions with epigenomic features specific to certain type of tissues or cells, for example, lineage-specific regulatory elements. Currently available tools do not directly address this question. This need motivated us to develop EpiCompare that allows investigators to easily identify regions with epigenetic features unique to specific epigenomes that they choose, making detection of common regulatory elements and/or cell type-specific regulatory elements an interactive and dynamic experience. Investigators can design their tests by choosing different combinations of epigenomes, and choosing different classification algorithms provided by our tool. EpiCompare will then identify regions with specified epigenomic features, and provide a quality assessment of the predictions. Investigators can interact with EpiCompare by investigating Roadmap Epigenomics data, or uploading their own data for comparison. Finally, prediction results can be readily visualized and further explored in the WashU Epigenome Browser.
The tool can be run in Chrome, Internet Explorer, and Firefox web browser. It can be run in Safari if used in a window without other web pages. Opening other pages in the same window in Safari with the tool will make the tool disconnected from the server.
Because the free shiny server can only allow one user at one time, to allow multiple users to use the tool simultaneously, we created 3 copies of the tool named EpiCompare1, EpiCompare2 and EpiCompare3 and used a load balancer named EpiCompare (epigenome.wustl.edu/EpiCompare/) to assign users to the 3 copies. This allows 3 users to use the tool at one time.
Below lists each step of using the tool and specific requirements for each step.
1.Here is a test file . Download the file to your local drive.
2.Upload this file locally. The file will be uploaded and processed.
3.After processing, the name of uploaded file will be listed as user-defined samples.
Select frequency cutoff, Fisher's exact test or k-means clustering method and the parameters for each method.
1) Frequency cutoff method: a region is defined as a positive region if the percentage of samples having the feature in the foreground samples is greater than or equal to a cutoff (default is 80%, called foreground cutoff) and the percentage of samples having the feature in the background samples is less than or equal to a cutoff (default is 20%, called background cutoff).
2) Fisher's exact test method: A region is defined as a positive region if the q-value from Fisher's exact test is less than a cutoff (default is 0.01, called q-value cutoff). When the number of foreground samples is small, Fisher’s exact test method cannot identify any regions with q-value threshold less than 0.01. In this case, investigators can use q-value as a ranking measure and obtain the top candidates by setting a high q-value cutoff.
3) K-means clustering method: Clusters specific for foreground samples should satisfy the following two conditions. First, the median of feature densities of foreground samples in this cluster is greater than or equal to a cutoff (default is 0.4, called foreground density cutoff); second, the median of feature densities of foreground samples is also greater than or equal to the percentile cutoff of feature densities of the background samples (default is 100%, which is the maximal feature density of the background samples, called percentile cutoff). The feature density in one cluster is the proportion of regions for one sample having the feature in the cluster. A value of 50% means half of the regions have the feature in the cluster.
Fisher's exact test method is not applicable when background samples are not specified. K-means clustering method is not applicable for analyzing uploaded data.
For example, use the default frequency cutoff method here.
This is the table of identified regions.
This is the validation results: enrichment for H3K27ac peaks and tissue enrichment index on H3K27ac.
This is the visualziation in Washu Epigenome Browser for an identified region.
Chang, C.W., et al. Identification of human housekeeping genes and tissue-selective genes by microarray meta-analysis. PLoS One 2011;6(7):e22859.
Leisch. A Toolbox for K-Centroids Cluster Analysis. Computational Statistics and Data Analysis, 51 (2), 526-544, 2006.
Pan, J.B., et al. PaGenBase: a pattern gene database for the global and dynamic understanding of gene function. PLoS One 2013;8(12):e80747.
Roadmap Epigenomics, C., et al. Integrative analysis of 111 reference human epigenomes. Nature 2015;518(7539):317-330.
Zhang, Y., et al. Model-based analysis of ChIP-Seq (MACS). Genome Biol 2008;9(9):R137.p>
Yanai, I., et al. Genome-wide midrange transcription profiles reveal expression level relationships in human tissue specification. Bioinformatics 2005;21(5):650-659.
Any questions are welcome. Please contact yu.he (at) wustl.edu .
A paper about EpiCompare is pubished in Bioinformatics journal. Please cite the tool as:
Yu He, Ting Wang; EpiCompare: An online tool to define and explore genomic regions with tissue or cell type-specific epigenomic features. Bioinformatics 2017 btx371. doi: 10.1093/bioinformatics/btx371