DESSO (DEep Sequence and Shape mOtif)

DESSO is a deep learning-based framework that can be used to accurately identify both sequence and shape regulatory motifs from the human genome. The performance of DESSO was evaluated on the 690 ChIP-seq datasets.

The DESSO database is online at: http://desso.osubmi.org/

Prerequisites and Dependencies

• Tensorflow 1.1.0 [Install]
• CUDA 8.0.44
• Python 2.7
• Biopython 1.7.0
• Scikit-learn
• Download GRCh37.p13.genome.fa and encode_101_background, then unzip them and put them into data/
• data/encode_101, data/encode_1001, and data/TfbsUniform_hg19_ENCODE only contain wgEncodeEH002288-related data as an example, owing to the file size limit. To access the source code and whole datasets (totally about 5.9GB) without additional manipulation, just click on code+whole data.

Model Training Based on Convolutional Neural Network (CNN)

Train CNN models on specified datasets:

cd code/
python train.py --start_index 0 --end_index 1 --peak_flank 50 --network CNN --feature_format Seq

--start_index 0 --end_index 1 indicates the first dataset (i.e., wgEncodeEH002288). For example, to train models for the second and third datasets, use --start_index 1 --end_index 3
--peak_flank 50 indicates the peak length is (2 * 50 + 1) = 101 base pairs
--network indicates that CNN is used here
--feature_format can be Seq or DNAShape, where Seq indicates the input is DNA sequences, DNAShape indicates the input is the combination of four DNA shape features (i.e., HelT, MGW, ProT, and Roll).

Output

If --feature_format Seq was used, the trained model can be found at /output/encode_101/gc_match/wgEncodeEH002288/Seq/CNN, together with Test_result.txt indicating the area under the receiver operating characteristic curve (AUC) of the trained model in predicting TF-DNA binding specificity on the test data.
If --feature_format DNAShape was used, the trained model is located at /output/encode_101/gc_match/wgEncodeEH002288/DNAShape/CNN.

Motif Prediction

Obtain either sequence or shape motifs based on the trained models above:

cd code/
python predict.py --start_index 0 --end_index 1 --peak_flank 50 --network CNN --feature_format Seq --start_cutoff 0.01 --end_cutoff 1 --step_cutoff 0.03

--feature_format Seq indicates that sequence motifs will be predicted. To identify shape motifs, use --feature_format DNAShape instead.

Output

For --feature_format Seq, the predicted sequence motifs are in output/encode_101/gc_match/wgEncodeEH002288/Seq/CNN/0.
For --feature_format DNAShape, four kinds of shape motifs would be predicted as shown in the following table:

Predict TF-DNA Binding Specicitity Using Gated-CNN (GCNN) and Long DNA Sequence

cd code/
python train.py --start_index 0 --end_index 1 --peak_flank 500 --network GCNN --feature_format Seq

--network GCNN indicates that GCNN is used for model training
--peak_flank 500 indicates that the peak length is (2 * 500 + 1) = 1001 base pairs

Output

The trained model and its AUC (Test_result.txt) on test data is located at output/encode_1001/gc_match/wgEncodeEH002288/Seq/GCNN.

Predict DNA motifs from your own ChIP-seq peaks

We will use /data/Fox01/fox01_peaks.bed as the example, note it will overwrite the original encode_tfbs.txt file:

• Download hg38.fa.gz, then unzip them and put them into data/
• Install bedtools, we will use this tool to extract DNA sequences from peak file

cd data/
wget http://hgdownload.soe.ucsc.edu/goldenPath/hg38/bigZips/hg38.fa.gz
gunzip hg38.fa.gz

cd ../code

python processing_peaks.py --name fox01_peaks.bed --peak_flank 50
python train.py --start_index 0 --end_index 1 --peak_flank 50 --network CNN --feature_format Seq
python predict.py --start_index 0 --end_index 1 --peak_flank 50 --network CNN --feature_format Seq --start_cutoff 0.01 --end_cutoff 1 --step_cutoff 0.03

Citation

If you use DESSO in your research, please cite the following paper:
Jinyu Yang, Anjun Ma, Adam D. Hoppe, Cankun Wang, Yang Li, Chi Zhang, Yan Wang, Bingqiang Liu, and Qin Ma,
"Prediction of regulatory motifs from human Chip-sequencing data using a deep learning framework",
Nucleic Acids Research 47, no. 15 (2019): 7809-7824.