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What is TAD-fusion score?

TAD-fusion score is a score to quantify deletions based on their potential disruption of the 3D genome structure. More specifically, TAD-fusion score is defined as the expected number of additional genomic interactions created as a result of the deletion.

How to calculate the TAD-fusion scores of a deletion set?

Option 1: From 5kb Hi-C data of GM12878 of Rao et al

  1. Compile the TAD-fusion score tool by running the script

    ./compile_cal_tad_fusion_score.sh

  2. Prepare the input deletion file (3-column format as the sample file, with hg19 as the reference)

  3. Run the tool with default parameters as

    ./../src/cal_tad_fusion_score -md ../Model/GM_Rao_5kb -f ../Data/disease_del.dat -mnl 10000 -mxl 5000000 -w 100 -d 0.06 -o Output/disease_del_TAD_fusion_score.dat

  4. The output file is "Output/disease_del_TAD_fusion_score.dat", the last column is the TAD-fusion score

  5. Sample scripts are in the folder Examples, here are options for calculating the TAD-fusion score

    -md       Model directory, model files must be renamed as chr1.model, chr2.model, ..., chrX.model 
-f        The file that stores deletions that we need to calculate the TAD-fusion score, the file format has three columns (e.g. one row is "chr2    221278232       223014332")
-mnl      The minimum length (a number of base pairs), any deletion that is shorter than this threshold will be skipped
-mxl      The maximum length, any deletion that is longer than this threshold will be skipped
-w        The window length (a number of bins) around the deletion to calculate the TAD-fusion score
-d        The delta value threshold to consider if a bin pair is interacted or not.
-o        The output file, the file format has four columns where the last one is the TAD-fusion score
Option 2: From a new Hi-C dataset

  1. Fit the model with Hi-C data

    • a. Install CPLEX

    • b. Set variables CPLEX_INCLUDE and CPLEX_LIB (in file make_fit_hic_model) to the directory where CPLEX is installed

    • c. Compile the source by running the script

      ./compile_fit_hic_model.sh

    • d. If the compilation is successful, an executable file "fit_hic_model" will be generated in the folder "src"

    • e. Options for fitting the model

       -fn       Data file path
 -ff       Data file format ("full_matrix_format" of Schmitt et al. data or "sparse_matrix_format" of Rao et al. data)
 -res      Hi-C matrix bin resolution (e.g. 40kb, 10kb, 5kb)
 -mn       Minimum distance (by a number of bins), any bin pair that the distance is shorter than this threshold will not be considered for fitting the model
 -mx       Maximum distance, any bin pair that the distance is longer than this threshold will not be considered for fitting the model
 -method   Method for fitting ("full" to fit the model from the whole Hi-C data at one time or "segmentation" to partition the matrix into segments and then fit the model for each segment)
 -sg       Length (i.e. a number of bins) of a segment (in the case the method is set to "segmentation")
 -mso      The minimum overlap (i.e. a number of bins) between two segments (in the case the method is set to "segmentation")
 -zero     A constant to replace the zero value to take the log
 -of       The output model file (the file format has 4 columns where alpha, beta, and the insulation are 1st, 3rd, 4th column respectively)

    • f. Example: The script file "fitting.sh" (in folder "Examples") is to fit the model of chr22 of GM12878 from Schmitt et al. data

      • Run the script by 
        cd Examples
./fitting.sh
      • The output model file is "GM12878.40kb.chr22.model" in folder "Examples/Output".
      • In the model file, 1st, 2nd and 4th columns are alpha, beta, and the insulator respectively.

    • g. For your convenience, we also provide models (in the folder "Model") that we fitted for GM12878 from Rao et al. data at 5kb resolution.

  2. Run TAD-fusion score tool (with the new model) to get the TAD-fusion score (as the section above)

Support

If you have any questions about TAD-fusion score, please contact Linh Huynh ([email protected]) or Fereydoun Hormozdiari ([email protected]).

Citation

Huynh L, Hormozdiari F. TAD-fusion score: discovery and ranking the contribution of deletions to genome structure. Genome Biology. 2019; 20:60.

Licence

See the LICENSE file for license rights and limitations (BSD-2).

Acknowledgement

This work is supported in part by the Sloan Research Fellowship number G-2017-9159 to Fereydoun Hormozdiari.