NuclearReceptorCistrome

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Introduction
 

Nuclear receptors are a class of transcription factors that can bind DNA directly in response to ligand induction. In concert with other proteins, nuclear receptors are involved in important physiological and pathological functions. Recently, the application of ChIP_chip/seq teachniques renders the accurate and effective dectection of nuclear receptor binding sites possible. We desinged a web-interface that enables the users to access and download the processed ChIP_chip/seq data of nuclear receptors, co-regulators and histone modifications. The web resources also includes processed differential expression data under ligand induction in conditions matched to ChIP_chip/seq data whenever possible. All the ChIP_chip/seq peak regions are annotated with enriched HRE and co-regulator motifs. A list of predicted hormone response genes from integration of nuclear receptor ChIP_chip/seq data and differential expression data is also readily available to the users.



Search input
 

On the search page users could select the species, cell origin, cell type, nuclear receptor and chromosome of the datasets they are interested in. The selection of co-regulators, epigenome, transcriptome, motif and targets information is optional. The genomic position input is also optional, and the input should be in the right format as "chr3:1-1000000". The input chromosome should exist for a certain species, and the input range should not exceed the chromosome length. Please note that the input range has offset 1, which means that the first position of the chromosome should be presented by 1. For efficiency reasons, the input chromosome range is limited to one million(1M) base pairs(bps).



Search output
 

If genomic position is not inputed, processed nuclear receptor data of the whole selected chromosome would be returned. The result page would include five options for each dataset:

  • "Download: WIG" to download the wiggle file with variable step for ChIP_chip datasets and fixed 30bp space for ChIP_seq datasets; the ChIP_chip wiggle file is converted from bar file using MAT group's unpublished bar2wig.py script.
  • "View: WIG" to view the wiggle file on UCSC genome browser; the file is displayed in vertical bars rather than default colored blocks; users could view additional information such as refseq genes by selecting certain customerized options in UCSC genome browser.
  • "Download: BED" to download the peak files in bed format with a 1e-5 pvalue cut-off.
  • "View: BED" to view the bed file in UCSC genome browser.
  • "Download:XLS" to download peak files in xls format with a 1e-5 pvalue cut-off; the xls files have additional information such as FDR values and peak summit positions, which are not included in the bed files. It is worth noting that for users' conveniences, all the above files are named by combined information of species, cell type, factor, condition, lab and chromosome number. For example, a bed file with the name "Human_MCF-7_ESR1_E2-45min_Brown_chr5.bed" includes the peaks in chromosome five of human ESR1 dataset generated by Dr. Brown's lab in MCF-7 cell line after 45 minutes treatment of estrogen.

    If co-regulators is selected, the result page would return transcription factor and PolII datasets in the chosen cell type. If epigenome option is selected, the result page would return the histone modification and nucleasome positioning datasets in the chosen cell type. If transcriptome option is selected, the result page would return the expression indexes and differential FDRs of genes in the matched condition as the nuclear receptor datasets. If motif option is selected, the result page would return HRE and co-regulator motif hit positions, each with a likelihood score for users to select their own cuts. If targets option is selected, the result page would return the predicted direct targets of the selected nuclear receptor in the selected cell type, each target gene being annotated with a simulated FDR value.

    If the genomic position is inputed, the result page would return files in the same formats as mentioned above, except that the files are not of the whole chromosome, but within the inputed chromosome range. To view all the ChIP peak and motif hit files at the same time in UCSC genome browser, users could just click on "Go to UCSC genome browser" option at the top of the page. Please pay attention that to limit the searching time to serveral seconds, we exclude the wiggle files in the returned page of selected chromosome range.



  • Browse
     

    Users could click on the "Browse" option in the top bar and go to the browse pages, which include the complete tables of cistrome, epigenome, transcriptome, motif and target datasets. Please note that only information of species, cell origin, cell type, factor, condition, reference and lab is included in the browse pages of cistrome, epigenome and transcriptome datasets. Users could access complete annotation of a dataset by querying on the search page. The browse pages have links for users to directly download zipped files encompassing results of all the chromosomes.



    Data visualization
     

    To download and view the ChIP_chip/seq datasets locally rather than in UCSC genome browser, users could download the sofware IGB and load each wiggle or bed file into the proper track: human data is in hg19 coordinates and mouse is in mm9 coodinates.