| Title: | Bayesian clustering and imputationa of single cell methylomes |
|---|---|
| Description: | Melissa is a Baysian probabilistic model for jointly clustering and imputing single cell methylomes. This is done by taking into account local correlations via a Generalised Linear Model approach and global similarities using a mixture modelling approach. |
| Authors: | C. A. Kapourani [aut, cre] |
| Maintainer: | C. A. Kapourani <[email protected]> |
| License: | GPL-3 | file LICENSE |
| Version: | 1.23.0 |
| Built: | 2024-12-18 03:26:46 UTC |
| Source: | https://github.com/bioc/Melissa |
Script for binarising CpG sites and formatting the coverage file so it can be directly used from the BPRMeth package. The format of each file is the following: <chr> <start> <met_level>, where met_level can be either 0 or 1. To read compressed files, e.g ending in .gz or .bz2, the R.utils package needs to be installed.
binarise_files(indir, outdir = NULL, format = 1, no_cores = NULL)binarise_files(indir, outdir = NULL, format = 1, no_cores = NULL)
indir |
Directory containing the coverage files, output from Bismark. |
outdir |
Directory to store the output files for each cell with exactly the same name. If NULL, then a directory called 'binarised' inside 'indir' will be create by default. |
format |
Integer, denoting the format of coverage file. When set to '1', the coverage file format is assumed to be: "<chr> <start> <end> <met_prcg> <met_reads> <unmet_reads>". When set to '2', then the format is assumed to be: "<chr> <start> <met_prcg> <met_reads> <unmet_reads>". |
no_cores |
Number of cores to use for parallel processing. If NULL, no parallel processing is used. |
No value is returned, the binarised data are stored in the outdir.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
filter_regions
## Not run: # Met directory met_dir <- "name_of_met_dir" binarise_files(met_dir) ## End(Not run)## Not run: # Met directory met_dir <- "name_of_met_dir" binarise_files(met_dir) ## End(Not run)
cluster_ari computes the clustering performance in terms
of the Adjusted Rand Index (ARI) metric.
cluster_ari(C_true, C_post)cluster_ari(C_true, C_post)
C_true |
True cluster assignemnts. |
C_post |
Posterior responsibilities of predicted cluster assignemnts. |
The clustering ARI.
C.A.Kapourani [email protected]
cluster_error computes the clustering assignment error, i.e. the
average number of incorrect cluster assignments:
Compute clustering assignment error
cluster_error computes the clustering assignment error, i.e. the
average number of incorrect cluster assignments:
cluster_error(C_true, C_post)cluster_error(C_true, C_post)
C_true |
True cluster assignemnts. |
C_post |
Posterior mean of predicted cluster assignemnts. |
The clustering assignment error
C.A.Kapourani [email protected]
Wrapper function for creating methylation regions for all cells, which is the input object for Melissa prior to filtering.
create_melissa_data_obj( met_dir, anno_file, chrom_size_file = NULL, chr_discarded = NULL, is_centre = FALSE, is_window = TRUE, upstream = -5000, downstream = 5000, cov = 5, sd_thresh = -1, no_cores = NULL )create_melissa_data_obj( met_dir, anno_file, chrom_size_file = NULL, chr_discarded = NULL, is_centre = FALSE, is_window = TRUE, upstream = -5000, downstream = 5000, cov = 5, sd_thresh = -1, no_cores = NULL )
met_dir |
Directory of (binarised) methylation files, each file corresponds to a single cell. |
anno_file |
The annotation file with 'tab' delimited format: "chromosome", "start", "end", "strand", "id", "name" (optional). Read the 'BPRMeth' documentation for more details. |
chrom_size_file |
Optional file name to read genome chromosome sizes. |
chr_discarded |
Optional vector with chromosomes to be discarded. |
is_centre |
Logical, whether 'start' and 'end' locations are pre-centred. If TRUE, the mean of the locations will be chosen as centre. If FALSE, the 'start' will be chosen as the center; e.g. for genes the 'start' denotes the TSS and we use this as centre to obtain K-bp upstream and downstream of TSS. |
is_window |
Whether to consider a predefined window region around centre. If TRUE, then 'upstream' and 'downstream' parameters are used, otherwise we consider the whole region from start to end location. |
upstream |
Integer defining the length of bp upstream of 'centre' for creating the genomic region. If is_window = FALSE, this parameter is ignored. |
downstream |
Integer defining the length of bp downstream of 'centre' for creating the genomic region. If is_window = FALSE, this parameter is ignored. |
cov |
Integer defining the minimum coverage of CpGs that each region must contain. |
sd_thresh |
Optional numeric defining the minimum standard deviation of the methylation change in a region. This is used to filter regions with no methylation variability. |
no_cores |
Number of cores to be used for parallel processing of data. |
A melissa_data_obj object, with the following elements:
met: A list of elements of length N, where N are
the total number of cells. Each element in the list contains another list
of length M, where M is the total number of genomic regions, e.g.
promoters. Each element in the inner list is an I X 2 matrix, where
I are the total number of observations. The first column contains the input
observations x (i.e. CpG locations) and the 2nd column contains the
corresponding methylation level.
anno_region: The annotation
object.
opts: A list with the parameters that were used for
creating the object.
C.A.Kapourani [email protected]
binarise_files, melissa,
filter_regions
## Not run: # Met directory met_dir <- "name_of_met_dir" # Annotation file name anno_file <- "name_of_anno_file" obj <- create_melissa_data_obj(met_dir, anno_file) # Extract annotation regions met <- obj$met # Extract annotation regions anno <- obj$anno_region ## End(Not run)## Not run: # Met directory met_dir <- "name_of_met_dir" # Annotation file name anno_file <- "name_of_anno_file" obj <- create_melissa_data_obj(met_dir, anno_file) # Extract annotation regions met <- obj$met # Extract annotation regions anno <- obj$anno_region ## End(Not run)
eval_cluster_performance is a wrapper function for
computing clustering performance in terms of ARI and clustering assignment
error.
eval_cluster_performance(obj, C_true)eval_cluster_performance(obj, C_true)
obj |
Output of Melissa inference object. |
C_true |
True cluster assignemnts. |
The 'melissa' object, with an additional slot named 'clustering', containing the ARI and clustering assignment error performance.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
filter_regions, eval_imputation_performance,
eval_cluster_performance
## Extract synthetic data dt <- melissa_synth_dt # Partition to train and test set dt <- partition_dataset(dt) # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) # Compute cluster performance melissa_obj <- eval_cluster_performance(melissa_obj, dt$opts$C_true) cat("ARI: ", melissa_obj$clustering$ari)## Extract synthetic data dt <- melissa_synth_dt # Partition to train and test set dt <- partition_dataset(dt) # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) # Compute cluster performance melissa_obj <- eval_cluster_performance(melissa_obj, dt$opts$C_true) cat("ARI: ", melissa_obj$clustering$ari)
eval_imputation_performance is a wrapper function for
computing imputation/clustering performance in terms of different metrics,
such as AUC and precision recall curves.
eval_imputation_performance(obj, imputation_obj)eval_imputation_performance(obj, imputation_obj)
obj |
Output of Melissa inference object. |
imputation_obj |
List containing two vectors of equal length, corresponding to true methylation states and predicted/imputed methylation states. |
The 'melissa' object, with an additional slot named 'imputation', containing the AUC, F-measure, True Positive Rate (TPR) and False Positive Rate (FPR), and Precision Recall (PR) curves.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
impute_test_met, filter_regions,
eval_imputation_performance,
eval_cluster_performance
# First take a subset of cells to efficiency # Extract synthetic data dt <- melissa_synth_dt # Partition to train and test set dt <- partition_dataset(dt) # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) imputation_obj <- impute_test_met(obj = melissa_obj, test = dt$met_test) melissa_obj <- eval_imputation_performance(obj = melissa_obj, imputation_obj = imputation_obj) cat("AUC: ", melissa_obj$imputation$auc)# First take a subset of cells to efficiency # Extract synthetic data dt <- melissa_synth_dt # Partition to train and test set dt <- partition_dataset(dt) # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) imputation_obj <- impute_test_met(obj = melissa_obj, test = dt$met_test) melissa_obj <- eval_imputation_performance(obj = melissa_obj, imputation_obj = imputation_obj) cat("AUC: ", melissa_obj$imputation$auc)
Given a list of observations, extract responses y
extract_y(X, coverage_ind)extract_y(X, coverage_ind)
X |
Observations |
coverage_ind |
Which observations have coverage |
The design matrix H
Fuctions for filter genomic regions due to (1) low CpG coverage, (2) low coverage across cells, or (3) low mean methylation variability.
filter_by_cpg_coverage(obj, min_cpgcov = 10) filter_by_coverage_across_cells(obj, min_cell_cov_prcg = 0.5) filter_by_variability(obj, min_var = 0.1)filter_by_cpg_coverage(obj, min_cpgcov = 10) filter_by_coverage_across_cells(obj, min_cell_cov_prcg = 0.5) filter_by_variability(obj, min_var = 0.1)
obj |
Melissa data object. |
min_cpgcov |
Minimum CpG coverage for each genomic region. |
min_cell_cov_prcg |
Threshold on the proportion of cells that have coverage for each region. |
min_var |
Minimum variability of mean methylation across cells, measured in terms of standard deviation. |
The (1) 'filter_by_cpg_coverage' function does not actually remove the region, it only sets NA to those regions. The (2) 'filter_by_coverage_across_cells' function keeps regions from which we can share information across cells. The (3) 'filter_by_variability' function keeps variable regions which are informative for cell subtype identification.
The filtered Melissa data object
C.A.Kapourani [email protected]
melissa, create_melissa_data_obj
# Run on synthetic data from Melissa package filt_obj <- filter_by_cpg_coverage(melissa_encode_dt, min_cpgcov = 20) # Run on synthetic data from Melissa package filt_obj <- filter_by_coverage_across_cells(melissa_encode_dt, min_cell_cov_prcg = 0.7) # Run on synthetic data from Melissa package filt_obj <- filter_by_variability(melissa_encode_dt, min_var = 0.1)# Run on synthetic data from Melissa package filt_obj <- filter_by_cpg_coverage(melissa_encode_dt, min_cpgcov = 20) # Run on synthetic data from Melissa package filt_obj <- filter_by_coverage_across_cells(melissa_encode_dt, min_cell_cov_prcg = 0.7) # Run on synthetic data from Melissa package filt_obj <- filter_by_variability(melissa_encode_dt, min_var = 0.1)
Make predictions of missing methylation states, i.e. perfrom
imputation using Melissa. Each file in the directory will be used as input
and a new file will be created in outdir with an additional column
containing the predicted met state (value between 0 and 1). Note that
predictions will be made only on annotation regions that were used
for training Melissa. Check impute_test_met, if you want to
make predictions only on test data.
impute_met_files( met_dir, outdir = NULL, obj, anno_region, basis = NULL, is_predictive = TRUE, no_cores = NULL )impute_met_files( met_dir, outdir = NULL, obj, anno_region, basis = NULL, is_predictive = TRUE, no_cores = NULL )
met_dir |
Directory of methylation files, each file corresponds to a
single cell. It should contain three columns <chr> <pos> <met_state>
(similar to the input required by |
outdir |
Directory to store the output files for each cell with exactly the same name. If NULL, then a directory called 'imputed' inside 'met_dir' will be created by default. |
obj |
Output of Melissa inference object. |
anno_region |
Annotation region object. This will be the outpuf of
|
basis |
Basis object, if NULL we perform imputation using Melissa,
otherwise using BPRMeth (then |
is_predictive |
Logical, use predictive distribution for imputation, or choose the cluster label with the highest responsibility. |
no_cores |
Number of cores to be used for parallel processing of data. |
A new directory outdir containing files (cells) with predicted
/ imputed methylation states per CpG location.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
filter_regions
## Not run: # Met directory met_dir <- "name_of_met_dir" # Annotation file name anno_file <- "name_of_anno_file" # Create data object melissa_data <- create_melissa_data_obj(met_dir, anno_file) # Run Melissa melissa_obj <- melissa(X = melissa_data$met, K = 2) # Annotation object anno_region <- melissa_data$anno_region # Peform imputation impute_met_dir <- "name_of_met_dir_for_imputing_cells" out <- impute_met_files(met_dir = impute_met_dir, obj = melissa_obj, anno_region = anno_region) ## End(Not run)## Not run: # Met directory met_dir <- "name_of_met_dir" # Annotation file name anno_file <- "name_of_anno_file" # Create data object melissa_data <- create_melissa_data_obj(met_dir, anno_file) # Run Melissa melissa_obj <- melissa(X = melissa_data$met, K = 2) # Annotation object anno_region <- melissa_data$anno_region # Peform imputation impute_met_dir <- "name_of_met_dir_for_imputing_cells" out <- impute_met_files(met_dir = impute_met_dir, obj = melissa_obj, anno_region = anno_region) ## End(Not run)
Make predictions of missing methylation states, i.e. perfrom
imputation using Melissa. This requires keepin a subset of data as a held
out test set during Melissa inference. If you want to impute a whole
directory containing cells (files) with missing methylation levels, see
impute_met_files.
impute_test_met( obj, test, basis = NULL, is_predictive = TRUE, return_test = FALSE )impute_test_met( obj, test, basis = NULL, is_predictive = TRUE, return_test = FALSE )
obj |
Output of Melissa inference object. |
test |
Test data to evaluate performance. |
basis |
Basis object, if NULL we perform imputation using Melissa, otherwise using BPRMeth. |
is_predictive |
Logical, use predictive distribution for imputation, or choose the cluster label with the highest responsibility. |
return_test |
Whether or not to return a list with the predictions. |
A list containing two vectors, the true methylation state and the predicted/imputed methylation states.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
filter_regions, eval_imputation_performance,
eval_cluster_performance
# Extract synthetic data dt <- melissa_synth_dt # Partition to train and test set dt <- partition_dataset(dt) # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter=10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) imputation_obj <- impute_test_met(obj = melissa_obj, test = dt$met_test)# Extract synthetic data dt <- melissa_synth_dt # Partition to train and test set dt <- partition_dataset(dt) # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter=10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) imputation_obj <- impute_test_met(obj = melissa_obj, test = dt$met_test)
Given a list of observations, initialise design matrices H for computational efficiency.
init_design_matrix(basis, X, coverage_ind)init_design_matrix(basis, X, coverage_ind)
basis |
Basis object. |
X |
Observations |
coverage_ind |
Which observations have coverage |
The design matrix H
log_sum_exp computes the log sum exp trick for avoiding
numeric underflow and have numeric stability in computations of small
numbers.
log_sum_exp(x)log_sum_exp(x)
x |
A vector of observations |
The logs-sum-exp value
C.A.Kapourani [email protected]
https://hips.seas.harvard.edu/blog/2013/01/09/computing-log-sum-exp/
melissa clusters and imputes single cells based on their
methylome landscape on specific genomic regions, e.g. promoters, using the
Variational Bayes (VB) EM-like algorithm.
melissa( X, K = 3, basis = NULL, delta_0 = NULL, w = NULL, alpha_0 = 0.5, beta_0 = NULL, vb_max_iter = 300, epsilon_conv = 1e-05, is_kmeans = TRUE, vb_init_nstart = 10, vb_init_max_iter = 20, is_parallel = FALSE, no_cores = 3, is_verbose = TRUE )melissa( X, K = 3, basis = NULL, delta_0 = NULL, w = NULL, alpha_0 = 0.5, beta_0 = NULL, vb_max_iter = 300, epsilon_conv = 1e-05, is_kmeans = TRUE, vb_init_nstart = 10, vb_init_max_iter = 20, is_parallel = FALSE, no_cores = 3, is_verbose = TRUE )
X |
The input data, which has to be a list of elements of
length N, where N are the total number of cells. Each element in the list
contains another list of length M, where M is the total number of genomic
regions, e.g. promoters. Each element in the inner list is an |
K |
Integer denoting the total number of clusters K. |
basis |
A 'basis' object. E.g. see create_basis function from BPRMeth package. If NULL, will an RBF object with 3 basis functions will be created. |
delta_0 |
Parameter vector of the Dirichlet prior on the mixing proportions pi. |
w |
Optional, an Mx(D)xK array of the initial parameters, where first dimension are the genomic regions M, 2nd the number of covariates D (i.e. basis functions), and 3rd are the clusters K. If NULL, will be assigned with default values. |
alpha_0 |
Hyperparameter: shape parameter for Gamma distribution. A Gamma distribution is used as prior for the precision parameter tau. |
beta_0 |
Hyperparameter: rate parameter for Gamma distribution. A Gamma distribution is used as prior for the precision parameter tau. |
vb_max_iter |
Integer denoting the maximum number of VB iterations. |
epsilon_conv |
Numeric denoting the convergence threshold for VB. |
is_kmeans |
Logical, use Kmeans for initialization of model parameters. |
vb_init_nstart |
Number of VB random starts for finding better initialization. |
vb_init_max_iter |
Maximum number of mini-VB iterations. |
is_parallel |
Logical, indicating if code should be run in parallel. |
no_cores |
Number of cores to be used, default is max_no_cores - 1. |
is_verbose |
Logical, print results during VB iterations. |
An object of class melissa with the following elements:
W: An (M+1) X K matrix with the optimized parameter
values for each cluster, M are the number of basis functions. Each column
of the matrix corresponds a different cluster k.
W_Sigma: A
list with the covariance matrices of the posterior parmateter W for each
cluster k.
r_nk: An (N X K) responsibility matrix of each
observations being explained by a specific cluster.
delta:
Optimized Dirichlet paramter for the mixing proportions.
alpha: Optimized shape parameter of Gamma distribution.
beta: Optimized rate paramter of the Gamma distribution
basis: The basis object.
lb: The lower bound vector.
labels: Cluster assignment labels.
pi_k:
Expected value of mixing proportions.
The modelling and mathematical details for clustering profiles using mean-field variational inference are explained here: http://rpubs.com/cakapourani/ . More specifically:
For Binomial/Bernoulli observation model check: http://rpubs.com/cakapourani/vb-mixture-bpr
For Gaussian observation model check: http://rpubs.com/cakapourani/vb-mixture-lr
C.A.Kapourani [email protected]
create_melissa_data_obj,
partition_dataset, plot_melissa_profiles,
impute_test_met, impute_met_files,
filter_regions
# Example of running Melissa on synthetic data # Create RBF basis object with 4 RBFs basis_obj <- BPRMeth::create_rbf_object(M = 4) set.seed(15) # Run Melissa melissa_obj <- melissa(X = melissa_synth_dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, vb_init_max_iter = 5, is_parallel = FALSE, is_verbose = FALSE) # Extract mixing proportions print(melissa_obj$pi_k)# Example of running Melissa on synthetic data # Create RBF basis object with 4 RBFs basis_obj <- BPRMeth::create_rbf_object(M = 4) set.seed(15) # Run Melissa melissa_obj <- melissa(X = melissa_synth_dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, vb_init_max_iter = 5, is_parallel = FALSE, is_verbose = FALSE) # Extract mixing proportions print(melissa_obj$pi_k)
Melissa: Bayesian clustering and imputation of single cell
methylomesBayesian clustering and imputation of single cell methylomes
.datatable.aware.datatable.aware
An object of class logical of length 1.
Melissa main package documentation.
C.A.Kapourani [email protected]
melissa, create_melissa_data_obj,
partition_dataset, plot_melissa_profiles,
filter_regions
Small synthetic ENCODE data generated by inferring methylation profiles from bulk ENCODE data, and subsequently generating single cells. It consists of N = 200 cells and M = 100 genomic regions. The data are in the required format for directly running Melissa and are used as a case study for the vignette.
melissa_encode_dtmelissa_encode_dt
A list object containing methylation regions, annotation data and the
options used for creating the data. This in general would be the output of
the create_melissa_data_obj function. It has the following
three objects:
met: A list containing the
methylation data, each element of the list is a different cell.
anno_region: Corresponding annotation data for each genomic region.
opts: Parameters/options used to generate the data.
Synthetic ENCODE methylation data
melissa_gibbs implements the Gibbs sampling algorithm
for performing clustering of single cells based on their DNA methylation
profiles, where the observation model is the Bernoulli distributed Probit
Regression likelihood. NOTE: that Gibbs sampling is really slow and we
recommend using the VB implementation: melissa.
melissa_gibbs( X, K = 2, pi_k = rep(1/K, K), w = NULL, basis = NULL, w_0_mean = NULL, w_0_cov = NULL, dir_a = rep(1, K), lambda = 1/2, gibbs_nsim = 1000, gibbs_burn_in = 200, inner_gibbs = FALSE, gibbs_inner_nsim = 50, is_parallel = TRUE, no_cores = NULL, is_verbose = FALSE )melissa_gibbs( X, K = 2, pi_k = rep(1/K, K), w = NULL, basis = NULL, w_0_mean = NULL, w_0_cov = NULL, dir_a = rep(1, K), lambda = 1/2, gibbs_nsim = 1000, gibbs_burn_in = 200, inner_gibbs = FALSE, gibbs_inner_nsim = 50, is_parallel = TRUE, no_cores = NULL, is_verbose = FALSE )
X |
A list of length I, where I are the total number of cells. Each element of the list contains another list of length N, where N is the total number of genomic regions. Each element of the inner list is an L x 2 matrix of observations, where 1st column contains the locations and the 2nd column contains the methylation level of the corresponding CpGs. |
K |
Integer denoting the number of clusters K. |
pi_k |
Vector of length K, denoting the mixing proportions. |
w |
A N x M x K array, where each column contains the basis function coefficients for the corresponding cluster. |
basis |
A 'basis' object. E.g. see create_rbf_object from BPRMeth package |
w_0_mean |
The prior mean hyperparameter for w |
w_0_cov |
The prior covariance hyperparameter for w |
dir_a |
The Dirichlet concentration parameter, prior over pi_k |
lambda |
The complexity penalty coefficient for penalized regression. |
gibbs_nsim |
Argument giving the number of simulations of the Gibbs sampler. |
gibbs_burn_in |
Argument giving the burn in period of the Gibbs sampler. |
inner_gibbs |
Logical, indicating if we should perform Gibbs sampling to sample from the augmented BPR model. |
gibbs_inner_nsim |
Number of inner Gibbs simulations. |
is_parallel |
Logical, indicating if code should be run in parallel. |
no_cores |
Number of cores to be used, default is max_no_cores - 1. |
is_verbose |
Logical, print results during EM iterations |
An object of class melissa_gibbs.
C.A.Kapourani [email protected]
melissa, create_melissa_data_obj,
partition_dataset, filter_regions
# Example of running Melissa Gibbs on synthetic data # Create RBF basis object with 4 RBFs basis_obj <- BPRMeth::create_rbf_object(M = 4) set.seed(15) # Run Melissa Gibbs melissa_obj <- melissa_gibbs(X = melissa_synth_dt$met, K = 2, basis = basis_obj, gibbs_nsim = 10, gibbs_burn_in = 5, is_parallel = FALSE, is_verbose = FALSE) # Extract mixing proportions print(melissa_obj$pi_k)# Example of running Melissa Gibbs on synthetic data # Create RBF basis object with 4 RBFs basis_obj <- BPRMeth::create_rbf_object(M = 4) set.seed(15) # Run Melissa Gibbs melissa_obj <- melissa_gibbs(X = melissa_synth_dt$met, K = 2, basis = basis_obj, gibbs_nsim = 10, gibbs_burn_in = 5, is_parallel = FALSE, is_verbose = FALSE) # Extract mixing proportions print(melissa_obj$pi_k)
Small synthetic data for quick analysis. It consists of N = 50 cells and M = 50 genomic regions.
melissa_synth_dtmelissa_synth_dt
A list object containing methylation regions, annotation data and the
options used for creating the data. This in general would be the output of
the create_melissa_data_obj function. It has the following
three objects:
met: A list containing the
methylation data, each element of the list is a different cell.
anno_region: Corresponding annotation data for each genomic region.
opts: Parameters/options used to generate the data.
Synthetic methylation data
Partition synthetic dataset to training and test set
partition_dataset( dt_obj, data_train_prcg = 0.5, region_train_prcg = 0.95, cpg_train_prcg = 0.5, is_synth = FALSE )partition_dataset( dt_obj, data_train_prcg = 0.5, region_train_prcg = 0.95, cpg_train_prcg = 0.5, is_synth = FALSE )
dt_obj |
Melissa data object |
data_train_prcg |
Percentage of genomic regions that will be fully used for training, i.e. across the whole region we will have no CpGs missing. |
region_train_prcg |
Fraction of genomic regions to keep for training set, i.e. some genomic regions will have no coverage at all during training. |
cpg_train_prcg |
Fraction of CpGs in each genomic region to keep for training set. |
is_synth |
Logical, whether we have synthetic data or not. |
The Melissa object with the following changes. The 'met' element will now contain only the 'training' data. An additional element called 'met_test' will store the data that will be used during testing to evaluate the imputation performance. These data will not be seen from Melissa during inference.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
filter_regions
# Partition the synthetic data from Melissa package dt <- partition_dataset(melissa_encode_dt)# Partition the synthetic data from Melissa package dt <- partition_dataset(melissa_encode_dt)
This function plots the predictive distribution of the methylation profiles inferred using the Melissa model. Each colour corresponds to a different cluster.
plot_melissa_profiles( melissa_obj, region = 1, title = "Melissa profiles", x_axis = "genomic region", y_axis = "met level", x_labels = c("Upstream", "", "Centre", "", "Downstream"), ... )plot_melissa_profiles( melissa_obj, region = 1, title = "Melissa profiles", x_axis = "genomic region", y_axis = "met level", x_labels = c("Upstream", "", "Centre", "", "Downstream"), ... )
melissa_obj |
Clustered cell subtypes using Melissa inference functions. |
region |
Genomic region number. |
title |
Plot title |
x_axis |
x axis label |
y_axis |
x axis label |
x_labels |
x axis ticks labels |
... |
Additional parameters |
A ggplot2 object.
C.A.Kapourani [email protected]
create_melissa_data_obj, melissa,
filter_regions, eval_imputation_performance,
eval_cluster_performance
# Extract synthetic data dt <- melissa_synth_dt # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) gg <- plot_melissa_profiles(melissa_obj, region = 10)# Extract synthetic data dt <- melissa_synth_dt # Create basis object from BPRMeth package basis_obj <- BPRMeth::create_rbf_object(M = 3) # Run Melissa melissa_obj <- melissa(X = dt$met, K = 2, basis = basis_obj, vb_max_iter = 10, vb_init_nstart = 1, is_parallel = FALSE, is_verbose = FALSE) gg <- plot_melissa_profiles(melissa_obj, region = 10)