CREMA
Cis-Regulatory Element Motif Activities

• The Cis-Regulatory Element Motif Activities is an online tool for automatically inferring regulatory networks from chromatin accessibility (ATC/DNase-seq) or enhancer mark (ChIP-seq) data.
• CREMA directly process raw data of a set of samples (FASTQ files).
• Using the chromatin state data across the samples, CREMA first identifies cis-regulatory elements genome-wide and then infers key transcription factors driving the observed chromatin state changes, and makes detailed predictions regarding their regulatory roles.
• Results include all identified CREs and, for each regulatory motif, inferred activities across the input samples, predicted genome-wide targets, CRE to gene associations, enriched pathways and functional classes of genes, and direct interactions between regulators.
• All results are presented within interactive and easily navigable HTML pages. Full results are also available for download.

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.

Instead of web-interface you can use CREMA uploader script which could be run from a command line on a remote server in headless mode.

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.

Using links/SRR Ids

Instead of local .fastq files you can provide links to fastq files which are publicly available in internet, or provide SRR Ids of samples from SRA archive. In such case you need to upload only the "samples.tsv" file. The CREMA server takes care of dowloading data from the internet according to links/database ids you provided. Please see example below:

 liver   fg      SRR123456
 liver   bg      SRR123457
 lung    fg      http://files.pub/EXDDF098.fastq.gz     http://files.pub/EXDDF103.fastq.gz
 lung    fg      ftp://files.pub/EXDDF099.fastq.gz
 lung    bg      ftp://files.pub/FGD_90KL01.fastq.gz   
                            

How to upload data:

Currently you can upload your data in two ways.

• Use web-interface. For that you need to click "Add files" button and select one or more files to add for upload. You can click this button multiple times. Once all your files are added check that appropriate optios are set correctly and click "Start upload" button.
• Use CREMA uploader. This is a python script which uploads your files to the server in headless mode and starts the analysis. You do not need browser or graphical user interface in order to use it. More information and download is here

If you experience any problems with the methods above please do not hesitate to contact us! There are other posibilities how you can share your data with us and we will find the most appropriate way for you.

Example results

• DNase-Seq: mouse liver sampled at different timepoints after prolonged exposure to constant darkness.
  • CREMA results
  • ENCODE link to the dataset
• ATAC-Seq: different tissues sampled at different timepoints during embryonic development.
  • CREMA results
  • ENCODE link to the dataset
• H3K4me3 ChIP-Seq: Immunoprecipitation for H3K4me3 across different tissues sampled at different timepoints during embryonic development.
  • CREMA results
  • ENCODE link to the dataset
• H3K4me3 ChIP-Seq: Immunoprecipitation for H3K4me3 across different types of primary human cells
  • CREMA results
  • ENCODE link to the dataset
• H3K4me1 ChIP-Seq: Immunoprecipitation for H3K4me1 across different types of primary human cells
  • CREMA results
  • ENCODE link to the dataset

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.

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