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 )
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. |
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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 |
A list where each entry is in BED format corresponding to the level of the hierarchy.
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.
#Read in data data("rao_chr20_25_rep") #Find TADs spec_table <- SpectralTAD(rao_chr20_25_rep, chr= 'chr20')#>#>#>#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.#> Warning: Unknown or uninitialised column: `Group`.