hicDifferentialTAD computes with a treatment Hi-C file, a control Hi-C file and a precomputed TAD domains file if the detected TADs are differential between the treatment and the control sample. The TADs need to be precomputed on the treatment file with _hicFindTADs.
hicDifferentialTAD extract per TAD three regions: the intra-TAD, the left and right inter-TAD region. In the following image, the upper visualization shows a region with the detected TADs which are indicated by the black lines. The bottom shows as an example which regions are used for the differential test: the intra-TAD region is highlighted in red, the left inter-TAD in sandy-color and the right inter-TAD in blue. Between two samples a Wilcoxon rank-sum test is applied for a TAD under H0: 'The regions are equal'. For all three regions of a TAD the rank-sum test is independently applied. The user has the choice with the two parameters 'mode' and 'modeReject' to define if a) all three regions should be considered ('all'), or only a subset e.g. the intra-TAD or intra-TAD and left inter-TAD should be considered; and b) if all regions need to have lower p-value than the user given to reject H0 or if it is enough that at least one region is rejecting H0 to consider the region as differential.
$ hicDifferentialTAD -tm GSM2644945_Untreated-R1.100000_chr1.cool -cm GSM2644947_Auxin2days-R1.100000_chr1.cool -td untreated_R1_domains.bed -o differential -p 0.01 -t 4 -mr allIn this example data from Nora et al. "Targeted Degradation of CTCF Decouples Local Insulation of Chromosome Domains from Genomic Compartmentalization", Cell 169.5 (2017): 930-944 is used [GEO: https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE98671]
The output are two BED-similar files: the '_accepted.diff_tad' and '_rejected.diff_tad' file. The difference to a real BED file is a) the usage of a header starting with '#', the first six columns are BED6 standard, however, there are three additional columns with the p-values of each intra-TAD, left-inter-TAD and right-inter-TAD test. The score value and name is copied from the domains.bed file which is a output of hicFindTADs.
# Created with HiCExplorer's hicDifferentialTAD version 3.5-dev
# H0 'regions are equal' H0 is rejected for all p-value smaller or equal the user given p-value threshold; i.e. regions in this file are considered as differential.
# Rejected regions with Wilcoxon rank-sum test to p-value: 0.01 with used mode: all and modeReject: all
# Chromosome start end name score strand p-value left-inter-TAD p-value right-inter-TAD p-value intra-TAD
chr1 4400000 6200000 ID_0.01_1 -0.5630275 . nan 0.42772134044376386 0.0001942482956610518
chr1 6200000 7300000 ID_0.01_2 -0.235798 . 0.3479058102348157 0.651801360704674 0.011174626122333891
chr1 7300000 9500000 ID_0.01_3 -0.44334 . 0.7619708385959597 0.9408966423531526 4.668547072331386e-06
chr1 10100000 11600000 ID_0.01_5 -0.6844015 . 0.10355136240139871 0.2022260523997077 0.006197912102328514
chr1 11600000 12900000 ID_0.01_6 -0.607587 . 0.39564035674322084 0.04934747494654432 5.069275897797787e-07
chr1 12900000 13700000 ID_0.01_7 -0.6303795 . 0.030328896271663634 0.048097680638217614 0.0023999817017426378
chr1 13700000 14900000 ID_0.01_8 -1.2063985 . 0.07605786424686575 0.5322636852613494 1.8146100883843892e-06
chr1 14900000 17100000 ID_0.01_9 -0.3406565 . 0.4982863585572014 0.692745144471043 0.002562121461829293
chr1 17100000 18100000 ID_0.01_10 -0.230354 . 0.8237750360973404 0.011911117420279341 0.00020602838341698515
chr1 18100000 19100000 ID_0.01_11 -0.5135365 . 0.007089417650089524 0.07553560212368073 0.03561337274424189