i-cisTarget

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Supply gene signature or ChIP peaks
1. Paste list of gene IDs or peak locations Please do not enter a single gene here, but a list of related genes. An explanation on supported input formats can be found here.
Or choose a file to upload:
2. For which species?
3. What features do you want to analyze? By default all available features are included.
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Extra and optional parameters
Input type
Extra databases (Optional)
Region mapping
Fraction of overlap
Enrichment-score threshold
Enrichment analysis
ROC threshold for AUC calculation
Threshold for visualization
Locations of true CRMs (Optional) Paste list of BED file entries.
Or choose a file to upload:
Also predict new targets?

Description

i-cisTarget enables:

to dissect a set of co-expressed genes into direct target genes of different transcription factor motifs.
to detect transcription factor motifs in a set of ChIP peaks.
to detect overrepresented in vivo features (iVF), e.g. histone modifications, for gene signatures and ChIP peaks. These iVFs help to improve motif discovery and candidate target gene prediction.

The analysis is based on ranking conserved regions in the Drosophila genome and recovery curves (See Figure), and works similarly to the Lever method on vertebrate genomes.

Some of the key features of i-cisTarget are:

over-represented motifs are predicted in the set of co-expressed genes, using entire intergenic and intronic sequences
12 Drosophila species are used
For motif scoring, the Cluster-Buster algorithm is used; kindly provided by Martin Frith.
For cross-species comparisons, the cluster-buster scores of orthologous regions are used independently (no requirement of base pair alignment of D. melanogaster motifs), as described previously here.
For significant motifs determines the optimal subset of genes that are predicted as direct targets
For the predicted direct targets, i-cisTarget presents the predicted enhancer and binding site locations in the UCSC Genome Browser.

A vast library of motifs and in vivo features was compiled for i-cisTarget. These features are:

6383 position weight matrices (PWM) are used, from various sources such as Transfac, Jaspar, FlyFactorSurvey, and motif collections from Stark et al., Elemento et al., and Down et al.
48 features from the BDTNP project.
455 features from the modENCODE project.
33 ChIP based features from Eileen Furlong's lab (Zinzen et al., Nature (2009)).
2 * 30 chromatin states (derived from the S2 and the BG3 cell lines) taken from modENCODE Consortium et al., Science (2010).

A full explanation of the method can be found in the following book chapter.

Citations

Stein Aerts, Xiao-Jiang Quan, Annelies Claeys, Marina Naval Sanchez, Phillip Tate, Jiekun Yan, and Bassem Hassan Robust target gene discovery through transcriptome perturbations and genome-wide enhancer predictions in Drosophila uncovers a regulatory basis for sensory specification PLoS Biology 2010 Jul 27;8(7):e1000435.
Delphine Potier, Zeynep Kalender Atak, Marina Naval Sanchez, Carl Herrmann, and Stein Aerts Using cisTargetX to Predict Transcriptional Targets and Networks in Drosophila Methods Mol Biol 2012; 786, 291–314.

Supported input formats

Report for a single gene signature

Gene signatures must be supplied as a list of gene identifiers, separated by newline characters.
The following IDs are supported:

FBgn numbers	CG numbers	Symbols
`FBgn0063210 FBgn0005666 FBgn0053099 FBgn0062476 FBgn0033182 FBgn0062469 FBgn0062468 FBgn0037804 FBgn0005536 FBgn0022772`	`CG1004 CG10108 CG10120 CG10160 CG10165 CG10257 CG10328 CG10508 CG10570 CG10581`	`pros CG13321 dpr7 mex1 lab toy bi SPoCk dpr7 CG11489`

Batch support for multiple gene signatures

The GMT file format is a tab delimited file format that describes multiple gene sets. In the GMT format each row represents a gene set. Each gene set is described by a name, a description, and the genes in the gene set. These fields are separated by a TAB character; the gene identifiers need to be separated by a semicolon, colon or again a TAB character.


                Signature1	Description	CG13728,barr,pho,Trl,gkt,abd-A,lab,chm,bab1,Pc,bab2,Pcl,Gint3,Dfd

                Signature2	Description	CG9248,RpS10b,CG14744,CG34168,CG8128,CG11899,ttk,CG12519,osk,CycK

ChIP peaks

ChIP peaks must be supplied as BED file entries, specifying the locations of these peaks in the Drosophila genome. FASTA file input is not supported.
An example of a BED file:


                    chr2L 11224674 11228405 FBgn0000011

                    chr2L 11226670 11230017 FBgn0000011

                    chr2L 11227952 11230482 FBgn0000011

                    chr2L 11207626 11210628 FBgn0000011

                    chr2R 16450050 16452858 FBgn0000044

                    chr2R 16447088 16450091 FBgn0000044

                    chr2R 16446613 16449597 FBgn0000044

                    chr2R 16450253 16453029 FBgn0000044

                    chr3R 9252216 9255339 FBgn0000046

                    chr3R 9253238 9255920 FBgn0000046

Examples

Genes expressed in proneural clusters (Analysis based on extended collection of 4238 motifs). The PPV and TPR values are calculated using a set of known proneural CRMs from REDFly.	Reeves & Posakony, Dev. Cell (2005)	Report
MEF2 ChIP peaks	Sandmann et al., Dev Cell (2006)	Report
FlyBase Termlink sets		Report

Cases

Example sets used in Aerts et al., PLoS Biology 2010

Dorsal downstream genes (Stathopoulos et al 2002) results
Ato downstream genes (GOF), upregulated genes results
Ato downstream genes (LOF), downregulated genes results
Sens downstream genes (GOF), downregulated genes results
Sens downstream genes (GOF), upregulated genes results
Genes expressed in proneural clusters (Reeves & Posakony, Dev. Cell 2005) results
Serpent GOF (Stramer et al 2008) results
Ey GOF (Ato independent) (Ostrin et al 2006) results
Biniou LOF + ChIP (Jakobsen et al 2007) results
MEF2 downstream genes from LOF microarray data (Sandmann et al 2006) result
Pointed GOF (Pointed Leading Edge PLE) (Philippakis et al 2006) results
GO:0007350 (blastoderm segmentation) results

Example sets used in Naval Sanchez et al., in preparation

Top 75 genes of cross species order statistics ranking results
Top 100 genes of cross species order statistics ranking results
Top 245 genes of cross species order statistics ranking results
Top 545 genes of cross species order statistics ranking results

Example sets used in Herrmann et al., in preparation

Highlights from the i-cisTarget analysis on a large compendium of 628 sets of genes that are co-expressed in the same cell type or anatomical structure in the fly (based on immunohistochemistry or in situ hybridization).

Cardioblast (FBbt:00001666)results
Pericardial cells (FBbt:00005058) results
Mushroom body (FBbt:00003684) and Kenyon cells (Fbbt:00003686; a child term of adult mushroom body) results