Cis-Regulatory Element Motif Activities

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CREMA is a completely automated tool for analyzing genome-wide DNA-accessibility (ATAC-seq/DNase-seq) or histone enhancers mark (ChIP-seq) samples. Using raw FASTQ files as input, CREMA first identifies all cis-regulatory elements (CREs) genome-wide that are active, i.e. accessible or carrying a histone mark, in at least one of the samples. It quantifies the signal intensity of each CRE in each sample, and identifies binding sites (TFBSs) for hundreds of transcription factors (TFs) in each CRE. Finally, it models the signal intensities of the CREs across the samples in terms of the predicted TFBSs and activities of TFs in each of the samples.

CREMA's results provide an integrated picture of the way in which the activities of transcriptional regulators drive the states of genome-wide cis-regulatory elements across the set of input samples. In particular, CREMA infers the relative importance of each TF in driving chromatin state changes across the samples, the activity of each TF across the samples, the set of genome-wide CREs and associated genes that are targeted by each TF, and pathways and functional classes that are enriched among the target genes of each CRE. The results are presented within interactive and easily navigable HTML pages and full results are available for download.

More extensive documentation and sample input data are provided under the "Usage" link. Please also note CREMA's "Terms of use"

How to run CREMA

The only input required to run CREMA is a set of raw .fastq files containing raw sequencing reads and a description of these files in TSV format (see below). Note that, as CREMA models changes in chromatin state across samples, it requires at least 2 input files. To add files for upload please click the "Add files" button and add files using the file selection dialog window. Before starting the upload process please select your data type (ChIP-Seq of histone marks or ATAC/DNase-Seq) and the organism from which the data derive. To start upload click the "Start upload" button. We strongly recommend to upload compressed (gzipped) fastq files in order to reduce upload time and minimize the probability of network errors. We also strongly suggest you provide an email address so that we can notify you when CREMA has finished analyzing the data, or contact you in case of problems with the submitted data. We will NOT share your email with any third parties. Finally, we recommend that you provide a name for your current submission in the project name field.

When the data upload has finished you will be automaticly redirected to the status page of the job. NOTE: if you have not provided your email address, please make sure to save the link to this page since it will redirect to the results when the CREMA analysis has finished.

TSV description file

In order to properly process the data, CREMA requires some information about the submitted data files to be submitted as a tab-separated text file. In particular, CREMA needs to know which files correspond to replicates of the same condition, and for paired-end reads it needs to know which files correspond to the paired ends of the same sample. In addition, for ChIP-seq we strongly recommend submitting corresponding background/input samples, and CREMA needs to know which samples are IP and which samples are background.

The "samples.tsv" file should be an ASCII, tab separated table with four columns. The file should have one line per sample and provide the following fields: The name of the condition (IMPORTANT: replicates should have the exact same condition name), the type of the sample (foreground/IP or background/input) indicated as 'fg' or 'bg', and the name(s) of the corresponding sequence read files. In case of paired-end sequences, two filenames corresponding to the first and second ends of the sequences should be given, whereas for single-end sequence data a single file name should be given. Note that mixtures of paired-end and single-end sequences are allowed. Finally, please use informative condition names since these will be used in the display of the results. Below is an example TSV file.

Example samples.tsv file

 liver   fg      Sample1_1.fastq.gz    Sample1_2.fastq.gz
 liver   fg      Sample2.fastq.gz
 liver   bg      Sample3.fastq.gz
 lung    fg      EXDDF098.fastq.gz     EXDDF103.fastq.gz
 lung    fg      EXDDF099.fastq.gz
 lung    bg      FGD_90KL01.fastq.gz   

Download example samples.tsv file.

Example results

Terms of use.

The developers of CREMA give permission to you and your institution to use the CREMA webserver for internal, research purposes, on the following conditions:

  1. The CREMA webserver will be used by you and/or your institution solely for non-commercial purposes, except with express permission from the authors.
  2. You may provide us with feedback on the use of the CREMA webserver in your research, and we are permitted to use any information you provide in making changes to CREMA.
  3. Any risk associated with using the CREMA webserver is with you and your institution.
  4. The CREMA webserver should be cited in any publication(s) reporting on data obtained by using it as:

Commercial users should contact us for licensing arrangements.