A bayesian variant of NMF algorithm to enable optimal inferences for the number of signatures through the automatic relevance determination technique. This functions delevers highly interpretable and sparse representations for both signature profiles and attributions at a balance between data fitting and model complexity (this method may introduce more signatures than expected, especially for copy number signatures (thus I don't recommend you to use this feature to extract copy number signatures)). See detail part and references for more.

sig_auto_extract(
  nmf_matrix = NULL,
  result_prefix = "BayesNMF",
  destdir = tempdir(),
  method = c("L1W.L2H", "L1KL", "L2KL"),
  strategy = c("stable", "optimal", "ms"),
  ref_sigs = NULL,
  K0 = 25,
  nrun = 10,
  niter = 2e+05,
  tol = 1e-07,
  cores = 1,
  optimize = FALSE,
  skip = FALSE,
  recover = FALSE
)

Arguments

nmf_matrix

a matrix used for NMF decomposition with rows indicate samples and columns indicate components.

result_prefix

prefix for result data files.

destdir

path to save data runs, default is tempdir().

method

default is "L1W.L2H", which uses an exponential prior for W and a half-normal prior for H (This method is used by PCAWG project, see reference #3). You can also use "L1KL" to set expoential priors for both W and H, and "L2KL" to set half-normal priors for both W and H. The latter two methods are originally implemented by SignatureAnalyzer software.

strategy

the selection strategy for returned data. Set 'stable' for getting optimal result from the most frequent K. Set 'optimal' for getting optimal result from all Ks. Set 'ms' for getting result with maximum mean cosine similarity with provided reference signatures. See ref_sigs option for details. If you want select other solution, please check get_bayesian_result.

ref_sigs

A Signature object or matrix or string for specifying reference signatures, only used when strategy = 'ms'. See Signature and sig_db options in get_sig_similarity for details.

K0

number of initial signatures.

nrun

number of independent simulations.

niter

the maximum number of iterations.

tol

tolerance for convergence.

cores

number of cpu cores to run NMF.

optimize

if TRUE, then refit the denovo signatures with QP method, see sig_fit.

skip

if TRUE, it will skip running a previous stored result. This can be used to extend run times, e.g. you try running 10 times firstly and then you want to extend it to 20 times.

recover

if TRUE, try to recover result from previous runs based on input result_prefix, destdir and nrun. This is pretty useful for reproducing result. Please use skip if you want to recover an unfinished job.

Value

a list with Signature class.

Details

There are three methods available in this function: "L1W.L2H", "L1KL" and "L2KL". They use different priors for the bayesian variant of NMF algorithm (see method parameter) written by reference #1 and implemented in SignatureAnalyzer software (reference #2).

I copied source code for the three methods from Broad Institute and supplementary files of reference #3, and wrote this higher function. It is more friendly for users to extract, visualize and analyze signatures by combining with other powerful functions in sigminer package. Besides, I implemented parallel computation to speed up the calculation process and a similar input and output structure like sig_extract().

References

Tan, Vincent YF, and Cédric Févotte. "Automatic relevance determination in nonnegative matrix factorization with the/spl beta/-divergence." IEEE Transactions on Pattern Analysis and Machine Intelligence 35.7 (2012): 1592-1605.

Kim, Jaegil, et al. "Somatic ERCC2 mutations are associated with a distinct genomic signature in urothelial tumors." Nature genetics 48.6 (2016): 600.

Alexandrov, Ludmil, et al. "The repertoire of mutational signatures in human cancer." BioRxiv (2018): 322859.

See also

sig_tally for getting variation matrix, sig_extract for extracting signatures using NMF package, sig_estimate for estimating signature number for sig_extract.

Author

Shixiang Wang

Examples

load(system.file("extdata", "toy_copynumber_tally_M.RData",
  package = "sigminer", mustWork = TRUE
))
res <- sig_auto_extract(cn_tally_M$nmf_matrix, result_prefix = "Test_copynumber", nrun = 1)
# At default, all run files are stored in tempdir()
dir(tempdir(), pattern = "Test_copynumber")
# \donttest{
laml.maf <- system.file("extdata", "tcga_laml.maf.gz", package = "maftools")
laml <- read_maf(maf = laml.maf)
mt_tally <- sig_tally(
  laml,
  ref_genome = "BSgenome.Hsapiens.UCSC.hg19",
  use_syn = TRUE
)

x <- sig_auto_extract(mt_tally$nmf_matrix,
  strategy = "ms", nrun = 3, ref_sigs = "legacy"
)
x
# }