GeneTrail 3.2

Regulator-target interactions (RTIs)

For our web server, we built an extensive collection of regulator-target gene interactions (RTIs) based on external databases: ChEA [1], ChIP-Atlas, ChipBase [2], ENCODE [3], Jaspar [4], Signalink [5] and TRANSFAC [6]. For each analysis users can decide which RTIs should be used for their computations.

Database content

The databases we used to build our collection of RTIs provide different levels of information on regulators and their target genes. Some databases provide manually curated RTIs extracted from primary literature while others provide binding information extracted from ChIP-Seq experiments. These binding sites are either provided as raw BED files that contain ChIP-Seq peaks or already processed data that contain information if a regulator binds in a predefined interval around the transcription start site (TSS) of given genes.

An overview of the RTIs provided by the different databases is shown in the following tables:

Data processing

In this section we describe the processing steps conducted to retrieve RTIs for the different databases.

ChEA

The ChEA database provides predefined collection of RTIs extracted from ChIP-Seq, ChIP-ChIP, ChIP-PET and DamID experiments. The entire collection was downloaded and converted to the RTI file format (see below).

ChIP-Atlas

The Chip-Atlas database contains processed ChIP-Seq data that provides information if a regulator binds in predefined intervals around the TSS of their target genes. We downloaded the entire sets and converted them to the RTI file format (see below).

• TSS -/+ 1000
• TSS -/+ 5000
• TSS -/+ 10000

ChipBase

ChipBase provides BED files that are already annotated with the distance to neighboring genes. We downloaded all BED files and extracted RTI sets for the following intervals:

• TSS -/+ 1000
• TSS -/+ 5000
• TSS -/+ 10000
• TSS -10000 / +1000

Encode and Jaspar

Encode and Jaspar provide raw BED files for a large number of ChIP-Seq experiments. All BED files were downloaded and processed using BEDTools [7] [8] to find regulator binding sites around the transcriptional start sites of all genes (protein coding and non-coding). The used gene annotations can be found in the overview table.

• TSS -/+ 1000
• TSS -/+ 5000
• TSS -/+ 10000
• TSS -10000 / +1000

Example usage:

bedtools window -a hg19TSS.bed -b peaks.bed -l 1000 -r 1000 -sw > annotated_peaks_tss_1000_1000.bed
bedtools window -a hg19TSS.bed -b peaks.bed -l 5000 -r 5000 -sw > annotated_peaks_tss_5000_5000.bed
bedtools window -a hg19TSS.bed -b peaks.bed -l 10000 -r 10000 -sw > annotated_peaks_tss_10000_10000.bed
bedtools window -a hg19TSS.bed -b peaks.bed -l 10000 -r 1000 -sw > annotated_peaks_tss_10000_1000.bed

SignaLink 2.0

SignaLink contains a predefined collection transcription factor binding information. All interactions were downloaded and converted to the RTI file format (see below).

TRANSFAC PRO / TRANSPRO

The TRANSFAC database contains manually curated RTIs extracted from primary literature as well as processed data extracted from ChIP and ChIP-ChIP experiments with regulator binding information in predefined promotor regions around the TSS of their target genes.

E2F5    PSMA2P1
E2F5    ZNF879
E2F5    OSMR-AS1
E2F5    CAMK1
E2F5    SPR
E2F5    ZNF700
E2F5    ZNF707
E2F5    CAMK4
E2F5    OR8A3P
E2F5    EDEM2
E2F5    ZC3H10
E2F5    RNF114
E2F5    ZC3H15

Bibliography