SPIN

SPIN (Spatial Position Inference of the Nuclear genome) is a integrative computational method to identify genome-wide chromosome localization patterns relative to multiple nuclearcompartments using TSA-seq, DamID, and Hi-C data.

Required Packages

SPIN requires the following Python packages to be installed:

• Python (tested on version 3.6)
• scikit-learn (tested on version 0.22.2)
• NumPy
• SciPy
• pandas
• pickle

Juicer tools is required to extract Hi-C data from .hic files. Requires Java Runtime Engine installed on your file system.

Usage

After install all dependencies, run the following python command:

python main.py -i <input_signal> --hic <hic_interactions> -w <window_size> -n <number_of_states> -o <output_path> -g <genome_bin> [--prev <previous_model>] [--save]

The options:

• -i <input_signal> : 1D genomic measurements of nuclear organization. input_signal file should be a tab-separated text file where each line is a vector of 1D genomic measurements. For example (header not included):

signal1	signal2	signal3	signal4
0.4209	-0.3468	-0.0405	0.01026
0.9098	-0.7316	-0.0961	0.0224
1.3589	-1.0421	-0.2001	0.0229
1.4688	-1.1082	-0.2716	0.0105
1.4552	-1.1599	-0.3605	-0.0345
1.3385	-1.1504	-0.3953	-0.0727
...	...	...	...

• --hic <hic_interactions> : List of Hi-C interactions added as edges in the model. hic_interactions file should be a tab-separated text file where the first two columns are the index numbers of genomic bins (needs to be consistent with genome_bin) and the third column is edge weight (opitional). For example (header not included):

bin1	bin2	weight
1	7	1.0
3	5	1.0
4	20	1.0
1	299	1.0
7	312	1.0
...	...	...

• -w <window_size> : Window size of each genome bin. Default = 100000

• -n <number_of_states> : Number of states to estimate for SPIN. Default = 5

• -o <output_path> : Output path.

• -g <genome_bin>: Genomic coordinates of each bin. genome_bin file should be a tab-separated text file where the first three columns are the genomic coordinates of each bin and the fourth column is the index number (starting from zero). For example (header not included):

chr	start	end	index number
chr1	0	25000	0
chr1	25000	50000	1
chr1	50000	75000	2
chr1	75000	100000	3
chr1	100000	125000	4
...	...	...	...

• --prev <previous_model>: (opitional) Load previously saved model.

• --save : (opitional) Save curent model to .pkl file.

Example:

python main.py -i input_chr1.txt --hic Hi-C_chr1.txt -w 25000 -n 5 -m <mode> -o example_chr1 -g bin_chr1.bed --save

Predicted states state_n can be found under output_path folder. To convert the results to bed format:

merge2bed.sh genome_bin_file state_n output.bed

Visualization

The bed file can be manually uploaded as custom annotation tracks to UCSC genome browser for visualization. An additional header must be added as the first line of the file in the following format:

track name='<track_name>' description='<description>' itemRgb='On'

Then go to a UCSC genome browser view, click the "add custom tracks" or "manage custom tracks" button below the tracks window. On the Add Custom Tracks page, load the annotation track data or URL for your custom track into the upper text box and the track documentation (optional) into the lower text box, then click the "Submit" button.

It is recommended to use distinguishable colors for different states. For example:

State	itemRgb
State_1	228,26,28
State_2	55,126,184
State_3	77,175,74
State_4	152,78,163
State_5	255,127,0
...	...

Additional BED fields can be added (with 9th column showing the color in RGB value). For example (header not included):

chrom	chromStart	chromEnd	name	score	strand	thickStart	thickEnd	itemRgb
chr1	0	725000	State_1	0	.	0	725000	102,194,165
chr1	725000	875000	State_2	0	.	725000	875000	252,141,98
chr1	875000	2550000	State_3	0	.	875000	2550000	141,160,203
chr1	2550000	2650000	State_2	0	.	2550000	2650000	252,141,98
chr1	2650000	2800000	State_1	0	.	2650000	2800000	102,194,165
chr1	2800000	2925000	State_2	0	.	2800000	2925000	252,141,98
...	...	...	...	...	...	...	...	...

Use the bedToBigBed utility to create a bigBed file.

bedToBigBed input.bed chrom.sizes myBigBed.bb

It is also recommended to use track bubs for more configurable custom annotations. See the track hub help page for more information.

In addition, tracks can be visualized on Nucleome Browser. See the Nucleome Browser help page for more instructions.

Data Availability

SPIN annotations for K562 can be found here.

Citation

If you use SPIN in your work

@article{wang2020spin,
  title={SPIN reveals genome-wide landscape of nuclear compartmentalization},
  author={Wang, Yuchuan and Zhang, Yang and Zhang, Ruochi and van Schaik, Tom and Zhang, Liguo and Sasaki, Takayo and Peric-Hupkes, Daniel and Chen, Yu and Gilbert, David M and van Steensel, Bas and others},
  journal={bioRxiv},
  year={2020},
  publisher={Cold Spring Harbor Laboratory}
}