diff --git a/docs/404.html b/docs/404.html index fa4e10d..9e59b98 100644 --- a/docs/404.html +++ b/docs/404.html @@ -72,6 +72,9 @@
  • Allele-specific Methylation
    • +
  • + CAMDAC Deconvolution Only +
  • diff --git a/docs/LICENSE.html b/docs/LICENSE.html index f0f7cfd..c21877a 100644 --- a/docs/LICENSE.html +++ b/docs/LICENSE.html @@ -55,6 +55,9 @@
  • Allele-specific Methylation
    • +
  • + CAMDAC Deconvolution Only +
  • Changelog diff --git a/docs/articles/allele-specific.html b/docs/articles/allele-specific.html index d2f4c8c..6947249 100644 --- a/docs/articles/allele-specific.html +++ b/docs/articles/allele-specific.html @@ -50,28 +50,31 @@
    • diff --git a/docs/articles/copy_number_alt.html b/docs/articles/copy_number_alt.html index 7facdd2..53df6d8 100644 --- a/docs/articles/copy_number_alt.html +++ b/docs/articles/copy_number_alt.html @@ -50,28 +50,31 @@ diff --git a/docs/articles/deconvolution.html b/docs/articles/deconvolution.html new file mode 100644 index 0000000..22059e2 --- /dev/null +++ b/docs/articles/deconvolution.html @@ -0,0 +1,201 @@ + + + + + + + +CAMDAC Deconvolution Only • CAMDAC + + + + + + + + + + + + +
    +
    + + + + +
    +
    +
    +

    CAMDAC Deconvolution Only

    + + + + + +
    + + + +
    +

    Deconvolution only +

    +

    The CAMDAC equation can be used to infer pure tumour DNA methylation rates, provided the following information is available per CpG:

    +
      +
    • Bulk tumour methylation rates
      • +
    • Tumour copy number state
      • +
    • Tumour purity
      • +
    +

    Here is an example for 5 CpGs from a single sample. Note: the normal copy number state is assumed diploid (2) in humans:

    +
    +
+# Set parameters
+bulk = c(0.3, 0.5, 0.2, 0.1, 0.9)
+normal = c(0.3, 0.9, 0.1, 0.7, 0.5)
+ploidy = c(2, 2, 1, 3, 4)
+purity = 0.8
+
+# Deconvolve methylation rates
+pure_meth = CAMDAC:::calculate_mt(bulk, normal, purity, ploidy)
+
+# Set clean rates based on threshold
+pure_meth_clean = dplyr::case_when(
+  pure_meth < 0 ~ 0,
+  pure_meth > 1 ~ 1,
+  TRUE ~ pure_meth
+)
    +

    After deconvolution, it may be useful to estimate the CpG coverage in the deconvolved tumour sample. Additionally, the highest density interval (HDI) of the methylation rate may be informative for quality control. These metrics can be calculated given additional information on bulk methylated and unmethylated read counts:

    +
    +
+# Optional: calculate effective coverage of the tumour
+# # Requires coverage per CpG in the bulk sample
+bulk_coverage = c(10, 20, 5, 15, 30)
+pure_effective_coverage = CAMDAC:::calculate_mt_cov(bulk_coverage, purity, ploidy)
+
+# Optional: calculate the HDI of the pure tumour methylation rate
+bulk_methylated_count = c(3, 10, 1, 2, 27)
+bulk_unmethylated_count = c(7, 10, 4, 13, 3)
+normal_methylated_count = c(3, 9, 1, 5, 2)
+normal_unmethylated_count = c(7, 11, 3, 8, 3)
+
+# HDI function (fast)
+CAMDAC:::hdi_norm_approx(
+  bulk_methylated_count,
+  bulk_unmethylated_count,
+  normal_methylated_count,
+  normal_unmethylated_count,
+  purity,
+  ploidy
+)
+
+# HDI function (most accurate)
+CAMDAC:::vec_HDIofMCMC_mt( 
+  bulk_methylated_count,
+  bulk_unmethylated_count,
+  normal_methylated_count,
+  normal_unmethylated_count,
+  purity,
+  ploidy,
+  credMass=0.99
+)
    +
    +
    + + + +
    + + + + +
    + + + + + + + + diff --git a/docs/articles/index.html b/docs/articles/index.html index 880a047..f80c80f 100644 --- a/docs/articles/index.html +++ b/docs/articles/index.html @@ -55,6 +55,9 @@
  • Allele-specific Methylation
    • +
  • + CAMDAC Deconvolution Only +
  • Changelog @@ -101,6 +104,8 @@

    Extra

    Allele-specific Methylation
    +
    CAMDAC Deconvolution Only
    +
    diff --git a/docs/articles/output.html b/docs/articles/output.html index 76f017b..e0add1a 100644 --- a/docs/articles/output.html +++ b/docs/articles/output.html @@ -50,28 +50,31 @@
    • diff --git a/docs/articles/panels.html b/docs/articles/panels.html index 856360e..f55b7f1 100644 --- a/docs/articles/panels.html +++ b/docs/articles/panels.html @@ -50,28 +50,31 @@ diff --git a/docs/articles/pipeline.html b/docs/articles/pipeline.html index bb6d015..6222125 100644 --- a/docs/articles/pipeline.html +++ b/docs/articles/pipeline.html @@ -50,28 +50,31 @@ diff --git a/docs/articles/questions.html b/docs/articles/questions.html index 5015bd1..a814743 100644 --- a/docs/articles/questions.html +++ b/docs/articles/questions.html @@ -50,28 +50,31 @@ diff --git a/docs/articles/setup.html b/docs/articles/setup.html index e28ffd0..0b52c62 100644 --- a/docs/articles/setup.html +++ b/docs/articles/setup.html @@ -50,28 +50,31 @@ diff --git a/docs/articles/visualisation.html b/docs/articles/visualisation.html index 120df16..51989cd 100644 --- a/docs/articles/visualisation.html +++ b/docs/articles/visualisation.html @@ -50,28 +50,31 @@ diff --git a/docs/authors.html b/docs/authors.html index 10e1030..d79b2c8 100644 --- a/docs/authors.html +++ b/docs/authors.html @@ -55,6 +55,9 @@
  • Allele-specific Methylation
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  • Allele-specific Methylation
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  • diff --git a/docs/news/index.html b/docs/news/index.html index acc56ba..2c63c78 100644 --- a/docs/news/index.html +++ b/docs/news/index.html @@ -32,28 +32,31 @@
  • diff --git a/docs/pkgdown.yml b/docs/pkgdown.yml index b971501..1cb5979 100644 --- a/docs/pkgdown.yml +++ b/docs/pkgdown.yml @@ -4,12 +4,12 @@ pkgdown_sha: 956f076f661eb2de9413f64ea24a580cf444466d articles: allele-specific: allele-specific.html copy_number_alt: copy_number_alt.html - deconvolution-only: deconvolution-only.html + deconvolution: deconvolution.html output: output.html panels: panels.html pipeline: pipeline.html questions: questions.html setup: setup.html visualisation: visualisation.html -last_built: 2024-07-23T15:17Z +last_built: 2024-07-23T15:27Z diff --git a/docs/reference/CamConfig.html b/docs/reference/CamConfig.html index b41ed9c..6ab676e 100644 --- a/docs/reference/CamConfig.html +++ b/docs/reference/CamConfig.html @@ -55,6 +55,9 @@
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  • Allele-specific Methylation
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  • Allele-specific Methylation
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  • Allele-specific Methylation
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  • Changelog diff --git a/docs/sitemap.xml b/docs/sitemap.xml index a261989..80312e0 100644 --- a/docs/sitemap.xml +++ b/docs/sitemap.xml @@ -15,6 +15,9 @@ /articles/copy_number_alt.html + + /articles/deconvolution.html + /articles/index.html diff --git a/vignettes/deconvolution.Rmd b/vignettes/deconvolution.Rmd new file mode 100644 index 0000000..9b3893a --- /dev/null +++ b/vignettes/deconvolution.Rmd @@ -0,0 +1,82 @@ +--- +title: "CAMDAC Deconvolution Only" +output: rmarkdown::html_vignette +vignette: > + %\VignetteIndexEntry{deconvolution} + %\VignetteEngine{knitr::rmarkdown} + %\VignetteEncoding{UTF-8} +--- + +```{r, include = FALSE} +knitr::opts_chunk$set( + collapse = TRUE, + comment = "#>", + eval = FALSE +) +``` + +## Deconvolution only + +The CAMDAC equation can be used to infer pure tumour DNA methylation rates, provided the following information is available per CpG: + +* Bulk tumour methylation rates +* Tumour copy number state +* Tumour purity + +Here is an example for 5 CpGs from a single sample. Note: the normal copy number state is assumed diploid (2) in humans: +```{r} + +# Set parameters +bulk = c(0.3, 0.5, 0.2, 0.1, 0.9) +normal = c(0.3, 0.9, 0.1, 0.7, 0.5) +ploidy = c(2, 2, 1, 3, 4) +purity = 0.8 + +# Deconvolve methylation rates +pure_meth = CAMDAC:::calculate_mt(bulk, normal, purity, ploidy) + +# Set clean rates based on threshold +pure_meth_clean = dplyr::case_when( + pure_meth < 0 ~ 0, + pure_meth > 1 ~ 1, + TRUE ~ pure_meth +) + +``` + +After deconvolution, it may be useful to estimate the CpG coverage in the deconvolved tumour sample. Additionally, the highest density interval (HDI) of the methylation rate may be informative for quality control. These metrics can be calculated given additional information on bulk methylated and unmethylated read counts: + +```{r} + +# Optional: calculate effective coverage of the tumour +# # Requires coverage per CpG in the bulk sample +bulk_coverage = c(10, 20, 5, 15, 30) +pure_effective_coverage = CAMDAC:::calculate_mt_cov(bulk_coverage, purity, ploidy) + +# Optional: calculate the HDI of the pure tumour methylation rate +bulk_methylated_count = c(3, 10, 1, 2, 27) +bulk_unmethylated_count = c(7, 10, 4, 13, 3) +normal_methylated_count = c(3, 9, 1, 5, 2) +normal_unmethylated_count = c(7, 11, 3, 8, 3) + +# HDI function (fast) +CAMDAC:::hdi_norm_approx( + bulk_methylated_count, + bulk_unmethylated_count, + normal_methylated_count, + normal_unmethylated_count, + purity, + ploidy +) + +# HDI function (most accurate) +CAMDAC:::vec_HDIofMCMC_mt( + bulk_methylated_count, + bulk_unmethylated_count, + normal_methylated_count, + normal_unmethylated_count, + purity, + ploidy, + credMass=0.99 +) +```