preciseTADhub 1.10.0
preciseTADhub is an ExperimentData R package that supplements the preciseTAD software R package. preciseTADhub offers users access to pre-trained random forest classification models used to predict TAD/loop boundary regions. The model building process introduced by preciseTAD (https://doi.org/10.1101/2020.09.03.282186) can be computationally intensive. To avoid this burden, we have provided users with 84 (2 cell lines \(\times\) 2 ground truth boundaries \(\times\) 21 autosomal chromosomes) .RDS files containing pre-trained models that can be leveraged to predict TAD and/or chromatin loop boundaries at base-level resolution using functionality provided by preciseTAD.
Each of the 84 files are stored as lists containing two objects: 1) a train object from with RF model information, and 2) a data.frame of variable importance for each genomic annotation included in the model. The file names are structured as follows:
\(i\)\(j\)\(k\)_\(l\).rds
where \(i\) denotes the chromosome that was used as a holdout {CHR1, CHR2, …, CHR21, CHR22} (i.e. for testing; meaning all other chromosomes were used for training), \(j\) denotes the cell line {GM12878, K562}, \(k\) denotes the resolution (size of genomic bins) {5kb, 10kb}, and \(l\) denotes the TAD/loop caller used to define ground truth {Arrowhead, Peakachu}.
For example the file named “CHR1_GM12878_5kb_Arrowhead.rds” is a list whose first item is a RF model that was built on data for chromosomes 2-22 (omitting CHR9; see https://doi.org/10.1101/2020.09.03.282186), binned using 5 kb bins, ground truth TAD boundaries were identified using the Arrowhead TAD caller at 5 kb on GM12878. All models included the same number of predictors including CTCF, RAD21, SMC3, and ZNF143. The second item in the list is a data.frame with variable importances for CTCF, RAD21, SMC3, and ZNF143.
The pre-trained models set up users to apply them to predict their own boundaries on chromosomes that were heldout, per the framework in the preciseTAD paper (https://doi.org/10.1101/2020.09.03.282186).
The following is an example of how to predict TAD boundaries at base-level resolution for CHR22 on GM12878, using a pre-trained model stored in preciseTADhub.
#if (!requireNamespace("BiocManager", quietly = TRUE))
#    install.packages("BiocManager")
#BiocManager::install(c("ExperimentHub"), version = "3.12")
library(ExperimentHub)
library(preciseTAD)
library(preciseTADhub)Table 1 shows the file names and the corresponding ExperimentHub (EH) IDs. Since we want to make TAD boundary predictions on CHR22 for GM12878, we opt to read in the “CHR22_GM12878_5kb_Arrowhead.rds” file. This corresponds to the EH3895 EHID.
| FileName | EHID | 
|---|---|
| CHR1_GM12878_5kb_Arrowhead.rds | EH3815 | 
| CHR1_GM12878_10kb_Peakachu.rds | EH3816 | 
| CHR1_K562_5kb_Arrowhead.rds | EH3817 | 
| CHR1_K562_10kb_Peakachu.rds | EH3818 | 
| CHR2_GM12878_5kb_Arrowhead.rds | EH3819 | 
| CHR2_GM12878_10kb_Peakachu.rds | EH3820 | 
| CHR2_K562_5kb_Arrowhead.rds | EH3821 | 
| CHR2_K562_10kb_Peakachu.rds | EH3822 | 
| CHR3_GM12878_5kb_Arrowhead.rds | EH3823 | 
| CHR3_GM12878_10kb_Peakachu.rds | EH3824 | 
| CHR3_K562_5kb_Arrowhead.rds | EH3825 | 
| CHR3_K562_10kb_Peakachu.rds | EH3826 | 
| CHR4_GM12878_5kb_Arrowhead.rds | EH3827 | 
| CHR4_GM12878_10kb_Peakachu.rds | EH3828 | 
| CHR4_K562_5kb_Arrowhead.rds | EH3829 | 
| CHR4_K562_10kb_Peakachu.rds | EH3830 | 
| CHR5_GM12878_5kb_Arrowhead.rds | EH3831 | 
| CHR5_GM12878_10kb_Peakachu.rds | EH3832 | 
| CHR5_K562_5kb_Arrowhead.rds | EH3833 | 
| CHR5_K562_10kb_Peakachu.rds | EH3834 | 
| CHR6_GM12878_5kb_Arrowhead.rds | EH3835 | 
| CHR6_GM12878_10kb_Peakachu.rds | EH3836 | 
| CHR6_K562_5kb_Arrowhead.rds | EH3837 | 
| CHR6_K562_10kb_Peakachu.rds | EH3838 | 
| CHR7_GM12878_5kb_Arrowhead.rds | EH3839 | 
| CHR7_GM12878_10kb_Peakachu.rds | EH3840 | 
| CHR7_K562_5kb_Arrowhead.rds | EH3841 | 
| CHR7_K562_10kb_Peakachu.rds | EH3842 | 
| CHR8_GM12878_5kb_Arrowhead.rds | EH3843 | 
| CHR8_GM12878_10kb_Peakachu.rds | EH3844 | 
| CHR8_K562_5kb_Arrowhead.rds | EH3845 | 
| CHR8_K562_10kb_Peakachu.rds | EH3846 | 
| CHR10_GM12878_5kb_Arrowhead.rds | EH3847 | 
| CHR10_GM12878_10kb_Peakachu.rds | EH3848 | 
| CHR10_K562_5kb_Arrowhead.rds | EH3849 | 
| CHR10_K562_10kb_Peakachu.rds | EH3850 | 
| CHR11_GM12878_5kb_Arrowhead.rds | EH3851 | 
| CHR11_GM12878_10kb_Peakachu.rds | EH3852 | 
| CHR11_K562_5kb_Arrowhead.rds | EH3853 | 
| CHR11_K562_10kb_Peakachu.rds | EH3854 | 
| CHR12_GM12878_5kb_Arrowhead.rds | EH3855 | 
| CHR12_GM12878_10kb_Peakachu.rds | EH3856 | 
| CHR12_K562_5kb_Arrowhead.rds | EH3857 | 
| CHR12_K562_10kb_Peakachu.rds | EH3858 | 
| CHR13_GM12878_5kb_Arrowhead.rds | EH3859 | 
| CHR13_GM12878_10kb_Peakachu.rds | EH3860 | 
| CHR13_K562_5kb_Arrowhead.rds | EH3861 | 
| CHR13_K562_10kb_Peakachu.rds | EH3862 | 
| CHR14_GM12878_5kb_Arrowhead.rds | EH3863 | 
| CHR14_GM12878_10kb_Peakachu.rds | EH3864 | 
| CHR14_K562_5kb_Arrowhead.rds | EH3865 | 
| CHR14_K562_10kb_Peakachu.rds | EH3866 | 
| CHR15_GM12878_5kb_Arrowhead.rds | EH3867 | 
| CHR15_GM12878_10kb_Peakachu.rds | EH3868 | 
| CHR15_K562_5kb_Arrowhead.rds | EH3869 | 
| CHR15_K562_10kb_Peakachu.rds | EH3870 | 
| CHR16_GM12878_5kb_Arrowhead.rds | EH3871 | 
| CHR16_GM12878_10kb_Peakachu.rds | EH3872 | 
| CHR16_K562_5kb_Arrowhead.rds | EH3873 | 
| CHR16_K562_10kb_Peakachu.rds | EH3874 | 
| CHR17_GM12878_5kb_Arrowhead.rds | EH3875 | 
| CHR17_GM12878_10kb_Peakachu.rds | EH3876 | 
| CHR17_K562_5kb_Arrowhead.rds | EH3877 | 
| CHR17_K562_10kb_Peakachu.rds | EH3878 | 
| CHR18_GM12878_5kb_Arrowhead.rds | EH3879 | 
| CHR18_GM12878_10kb_Peakachu.rds | EH3880 | 
| CHR18_K562_5kb_Arrowhead.rds | EH3881 | 
| CHR18_K562_10kb_Peakachu.rds | EH3882 | 
| CHR19_GM12878_5kb_Arrowhead.rds | EH3883 | 
| CHR19_GM12878_10kb_Peakachu.rds | EH3884 | 
| CHR19_K562_5kb_Arrowhead.rds | EH3885 | 
| CHR19_K562_10kb_Peakachu.rds | EH3886 | 
| CHR20_GM12878_5kb_Arrowhead.rds | EH3887 | 
| CHR20_GM12878_10kb_Peakachu.rds | EH3888 | 
| CHR20_K562_5kb_Arrowhead.rds | EH3889 | 
| CHR20_K562_10kb_Peakachu.rds | EH3890 | 
| CHR21_GM12878_5kb_Arrowhead.rds | EH3891 | 
| CHR21_GM12878_10kb_Peakachu.rds | EH3892 | 
| CHR21_K562_5kb_Arrowhead.rds | EH3893 | 
| CHR21_K562_10kb_Peakachu.rds | EH3894 | 
| CHR22_GM12878_5kb_Arrowhead.rds | EH3895 | 
| CHR22_GM12878_10kb_Peakachu.rds | EH3896 | 
| CHR22_K562_5kb_Arrowhead.rds | EH3897 | 
| CHR22_K562_10kb_Peakachu.rds | EH3898 | 
Suppose we want to read in the model that was built using CHR1-CHR21, on GM12878, using Arrowhead defined TAD boundaries at 5kb resolution. We can do this with the following wrapper function. Note: you must initialize ExperimentHub first.
#Initialize ExperimentHub
hub <- ExperimentHub()
query(hub, "preciseTADhub")## ExperimentHub with 84 records
## # snapshotDate(): 2023-10-24
## # $dataprovider: preciseTAD
## # $species: Homo sapiens
## # $rdataclass: list
## # additional mcols(): taxonomyid, genome, description,
## #   coordinate_1_based, maintainer, rdatadateadded, preparerclass, tags,
## #   rdatapath, sourceurl, sourcetype 
## # retrieve records with, e.g., 'object[["EH3815"]]' 
## 
##            title                          
##   EH3815 | CHR1_GM12878_5kb_Arrowhead.rds 
##   EH3816 | CHR1_GM12878_10kb_Peakachu.rds 
##   EH3817 | CHR1_K562_5kb_Arrowhead.rds    
##   EH3818 | CHR1_K562_10kb_Peakachu.rds    
##   EH3819 | CHR2_GM12878_5kb_Arrowhead.rds 
##   ...      ...                            
##   EH3894 | CHR21_K562_10kb_Peakachu.rds   
##   EH3895 | CHR22_GM12878_5kb_Arrowhead.rds
##   EH3896 | CHR22_GM12878_10kb_Peakachu.rds
##   EH3897 | CHR22_K562_5kb_Arrowhead.rds   
##   EH3898 | CHR22_K562_10kb_Peakachu.rdsmyfiles <- query(hub, "preciseTADhub")
CHR22_GM12878_5kb_Arrowhead <- readEH(chr = "CHR22", cl = "GM12878", gt = "Arrowhead", source = myfiles)data("tfbsList")
# Restrict the data matrix to include only SMC3, RAD21, CTCF, and ZNF143
tfbsList_filt <- tfbsList[names(tfbsList) %in% c("Gm12878-Ctcf-Broad", 
                                            "Gm12878-Rad21-Haib",
                                            "Gm12878-Smc3-Sydh",
                                            "Gm12878-Znf143-Sydh")]
names(tfbsList_filt) <- c("Ctcf", "Rad21", "Smc3", "Znf143")
# Run preciseTAD
set.seed(123)
pt <- preciseTAD(genomicElements.GR = tfbsList_filt,
                featureType         = "distance",
                CHR                 = "CHR22",
                chromCoords         = list(18000000, 19000000),
                tadModel            = CHR22_GM12878_5kb_Arrowhead,
                threshold           = 1.0,
                verbose             = FALSE,
                parallel            = NULL,
                DBSCAN_params       = list(30000, 3))
                # flank               = 5000)
                # genome              = "hg19")
pt## $preciseTADparams
##   MinPts   eps NEmean k
## 1      3 30000    4.8 5
## 
## $PTBR
## GRanges object with 5 ranges and 0 metadata columns:
##       seqnames            ranges strand
##          <Rle>         <IRanges>  <Rle>
##   [1]    chr22 18038169-18038406      *
##   [2]    chr22 18268086-18268246      *
##   [3]    chr22 18310018-18312978      *
##   [4]    chr22 18499231-18507447      *
##   [5]    chr22 18557665-18559050      *
##   -------
##   seqinfo: 1 sequence from an unspecified genome; no seqlengths
## 
## $PTBP
## GRanges object with 5 ranges and 0 metadata columns:
##       seqnames    ranges strand
##          <Rle> <IRanges>  <Rle>
##   [1]    chr22  18038310      *
##   [2]    chr22  18268166      *
##   [3]    chr22  18312917      *
##   [4]    chr22  18507320      *
##   [5]    chr22  18558977      *
##   -------
##   seqinfo: 1 sequence from an unspecified genome; no seqlengths
## 
## $Summaries
## $Summaries$PTBRWidth
##   min  max median  iqr   mean       sd
## 1 161 8217   1386 2723 2592.6 3342.241
## 
## $Summaries$PTBRCoverage
##         min       max     median       iqr      mean        sd
## 1 0.0230011 0.8385093 0.08730159 0.6643423 0.3392469 0.3986859
## 
## $Summaries$DistanceBetweenPTBR
##     min    max   median      iqr     mean       sd
## 1 41772 229680 118235.5 149003.2 126980.8 95242.47
## 
## $Summaries$NumSubRegions
##   min max median iqr mean      sd
## 1   2  16      3   1  5.6 5.85662
## 
## $Summaries$SubRegionWidth
##   min max median iqr     mean       sd
## 1   1 162      6 9.5 26.28571 45.35037
## 
## $Summaries$DistBetweenSubRegions
##   min  max median   iqr     mean       sd
## 1   3 2957     58 612.5 532.6087 871.3022
## 
## $Summaries$NormilizedEnrichment
## [1] 4.8
## 
## $Summaries$BaseProbs
## [1] NA