,
Kellen Cresswell [aut],
John Stansfield [aut]| Title: | SpectralTAD: Hierarchical TAD detection using spectral clustering |
|---|---|
| Description: | SpectralTAD is an R package designed to identify Topologically Associated Domains (TADs) from Hi-C contact matrices. It uses a modified version of spectral clustering that uses a sliding window to quickly detect TADs. The function works on a range of different formats of contact matrices and returns a bed file of TAD coordinates. The method does not require users to adjust any parameters to work and gives them control over the number of hierarchical levels to be returned. |
| Authors: | Mikhail Dozmorov [aut, cre] ,
Kellen Cresswell [aut],
John Stansfield [aut] |
| Maintainer: | Mikhail Dozmorov <[email protected]> |
| License: | MIT + file LICENSE |
| Version: | 1.23.0 |
| Built: | 2024-11-19 04:28:03 UTC |
| Source: | https://github.com/bioc/SpectralTAD |
A sparse 3-column contact matrix
data(rao_chr20_25_rep)data(rao_chr20_25_rep)
A data.frame with 3 columns and 2125980 rows:
The genomic loci corresponding to a given row of the contact matrix
The genomic loci corresponding to a given column of the contact matrix
Number of contacts between Loci1 and Loci2
A data.frame
Data from Rao SS, Huntley MH, Durand NC, Stamenova EK et al. A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 2014 Dec 18;159(7):1665-80. PMID: 25497547. Available at https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE63525
Hierarchical Spectral Clustering of TADs
SpectralTAD( cont_mat, chr, levels = 1, qual_filter = FALSE, z_clust = FALSE, eigenvalues = 2, min_size = 5, window_size = 25, resolution = "auto", gap_threshold = 1, grange = FALSE, out_format = "none", out_path = chr )SpectralTAD( cont_mat, chr, levels = 1, qual_filter = FALSE, z_clust = FALSE, eigenvalues = 2, min_size = 5, window_size = 25, resolution = "auto", gap_threshold = 1, grange = FALSE, out_format = "none", out_path = chr )
cont_mat |
Contact matrix in either sparse 3 column, n x n or n x (n+3) form where the first three columns are coordinates in BED format. If an x n matrix is used, the column names must correspond to the start point of the corresponding bin. If large mode is selected, then this matrix must be a tab-seperated n x n or n x (n+3) and it should be the path to a contact matrix. Required. |
chr |
The chromosome of the contact matrix being analyzed. Required. |
levels |
The number of levels of the TAD hierarchy to be calculated. The default setting is 1. |
qual_filter |
Option to turn on quality filtering which removes TADs with negative silhouette scores (poorly organized TADs). Default is FALSE. |
z_clust |
Option to filter sub-TADs based on the z-score of their eigenvector gaps. Default is TRUE. |
eigenvalues |
The number of eigenvectors to be calculated. The default and suggested setting is 2. |
min_size |
The minimum allowable TAD size measured in bins. Default is 5. |
window_size |
The size of the sliding window for calculating TADs. Smaller window sizes correspond to less noise from long-range contacts but limit the possible size of TADs |
resolution |
The resolution of the contact matrix. If none selected, the resolution is estimated by taking the most common distance between bins. For n x (n+3) contact matrices, this value is automatically calculated from the first three columns. |
gap_threshold |
Corresponds to the percentage of zeros allowed before a column/row is removed from the analysis. 1=100%, .7 = 70%, etc. Default is 1. |
grange |
Parameter to determine whether the result should be a GRangeList object. Defaults to FALSE |
out_format |
Specifies the format of the file which SpectralTAD outputs. If "none, no file is output. "juicebox" or "bedpe" returns a bedpe file compatible with juicebox. "hicexplorer" or "bed" returns a bed file compatible with hicexplorer. Default is none |
out_path |
Path of output file. Default is the chromosome |
Given a sparse 3 column, an n x n contact matrix, or n x (n+3) contact matrix, SpectralTAD returns a list of TAD coordinates in BED format. SpectralTAD works by using a sliding window that moves along the diagonal of the contact matrix. By default, we use the biologically relevant maximum TAD size of 2Mb and minimum size of 5 bins to determine the size of this window. Within each window, we calculate a Laplacian matrix and determine the location of TAD boundaries based on gaps between eigenvectors calculated from this matrix. The number of TADs in a given window is calculated by finding the number that maximizes the silhouette score. A hierarchy of TADs is created by iteratively applying the function to sub-TADs. The number of levels in each hierarchy is determined by the user.
A list where each entry is in BED format corresponding to the level of the hierarchy.
#Read in data data("rao_chr20_25_rep") #Find TADs spec_table <- SpectralTAD(rao_chr20_25_rep, chr= 'chr20')#Read in data data("rao_chr20_25_rep") #Find TADs spec_table <- SpectralTAD(rao_chr20_25_rep, chr= 'chr20')
Parallelized Hierarchical Spectral Clustering of TADs
SpectralTAD_Par( cont_list, chr, levels = 1, qual_filter = FALSE, z_clust = FALSE, eigenvalues = 2, min_size = 5, window_size = 25, resolution = "auto", grange = FALSE, gap_threshold = 1, cores = "auto", labels = NULL )SpectralTAD_Par( cont_list, chr, levels = 1, qual_filter = FALSE, z_clust = FALSE, eigenvalues = 2, min_size = 5, window_size = 25, resolution = "auto", grange = FALSE, gap_threshold = 1, cores = "auto", labels = NULL )
cont_list |
List of contact matrices where each is in either sparse 3 column, n x n or n x (n+3) form, where the first 3 columns are chromosome, start and end coordinates of the regions. If an x n matrix is used, the column names must correspond to the start point of the corresponding bin. Required. |
chr |
Vector of chromosomes in the same order as their corresponding contact matrices. Must be same length as cont_list. Required. |
levels |
The number of levels of the TAD hierarchy to be calculated. The default setting is 1. |
qual_filter |
Option to turn on quality filtering which removes TADs with negative silhouette scores (poorly organized TADs). Default is FALSE. |
z_clust |
Option to filter sub-TADs based on the z-score of their eigenvector gaps. Default is TRUE. |
eigenvalues |
The number of eigenvectors to be calculated. The default and suggested setting is 2. |
min_size |
The minimum allowable TAD size measured in bins. Default is 5. |
window_size |
The size of the sliding window for calculating TADs. Smaller window sizes correspond to less noise from long-range contacts but limit the possible size of TADs |
resolution |
The resolution of the contact matrix. If none selected, the resolution is estimated by taking the most common distance between bins. For n x (n+3) contact matrices, this value is automatically calculated from the first 3 columns. |
grange |
Parameter to determine whether the result should be a GRangeList object. Defaults to FALSE |
gap_threshold |
Corresponds to the percentage of zeros allowed before a column/row is removed from analysis. 1=100%, .7 = 70%, etc. Default is 1. |
cores |
Number of cores to use. Defaults to total available cores minus one. |
labels |
Vector of labels used to name each contact matrix. Must be same length as cont_list. Default is NULL. |
This is the parallelized version of the SpectralTAD() function. Given a sparse 3 column, an n x n contact matrix, or n x (n+3) contact matrix, SpectralTAD returns a list of TAD coordinates in BED format. SpectralTAD works by using a sliding window that moves along the diagonal of the contact matrix. By default we use the biologically relevant maximum TAD size of 2Mb and minimum size of 5 bins to determine the size of this window. Within each window, we calculate a Laplacian matrix and determine the location of TAD boundaries based on gaps between eigenvectors calculated from this matrix. The number of TADs in a given window is calculated by finding the number that maximize the silhouette score. A hierarchy of TADs is created by iteratively applying the function to sub-TADs. The number of levels in each hierarchy is determined by the user.
List of lists where each entry is a list of data frames or GRanges in BED format corresponding to TADs seperated by hierarchies
#Read in data data("rao_chr20_25_rep") #Make a list of matrices mat_list = list(rao_chr20_25_rep, rao_chr20_25_rep) #Make a vector of chromosomes chr = c("chr20", "chr20") #Make a vector of labels labels = c("run1", "run2") spec_table <- SpectralTAD_Par(mat_list, chr= chr, labels = labels, cores = 2)#Read in data data("rao_chr20_25_rep") #Make a list of matrices mat_list = list(rao_chr20_25_rep, rao_chr20_25_rep) #Make a vector of chromosomes chr = c("chr20", "chr20") #Make a vector of labels labels = c("run1", "run2") spec_table <- SpectralTAD_Par(mat_list, chr= chr, labels = labels, cores = 2)