<p>My question was kindly answered by Biostars user <a href="https://www.biostars.org/p/9545804/#9545835" rel="nofollow noreferrer">Papyrus</a>, who pointed out that a GC in the 5' to 3' direction is a GpC dinucleotide, not a CpG dinucleotide. GpC dinucleotides are then biologically and chemically distinct from CpG dinucleotides, due to the directionality of the DNA polymer.</p>

CC BY-SA 4.0
2022-11-28T08:07:38.090Z
2022-11-28T08:07:38.090Z
ning
<p>CpGs are symmetrical, in that a CG sequence on the forward strand is hybridized to a GC --- and both dinucleotides on each opposing strand are CpGs dinucleotides which can be methylated. Conversely, CpGs can be GC on the forward strand but CG on the reverse strand.</p>
<pre><code>FORWARD -&gt; 5'--CG--3'  [OR]  5'--GC--3' &lt;- FORWARD
REVERSE -&gt; 3'--GC--5'        3'--CG--5' &lt;- REVERSE
</code></pre>
<p>The assignment of &quot;forward&quot; and &quot;reverse&quot; strandedness is more or less arbitrary.</p>
<p>Given the above, why does it seem like the Illumina 850k (aka EPIC) array only profiles methylation from CpGs which are CG in the forward strand, while ignoring CpGs which are GC in the forward strand? I would also love to hear if my premises are wrong.</p>
<p>Here is some R code illustrating the issue at hand:</p>
<pre><code>suppressPackageStartupMessages({
  library(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
  library(tidyverse)})
data(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)

IlluminaHumanMethylationEPICanno.ilm10b4.hg19 %&gt;%
  getAnnotation() %&gt;%
  as_tibble() %&gt;%
  count(forward_seq=str_extract(Forward_Sequence, &quot;\\[[ATCG]{2}\\]&quot;))

# Results:
# # A tibble: 3 × 2
#   forward_seq      n
#   &lt;chr&gt;        &lt;int&gt;
# 1 [CA]          2922
# 2 [CG]        862927
# 3 [CT]            10
<span class="math-container">```</span>
</code></pre>

CC BY-SA 4.0
2022-11-20T15:08:24.217Z
I cross-posted this to Biostars: https://www.biostars.org/p/9545804/
ning
<genome><database><sequence-annotation><genomics><public-databases>
Why do Illumina 850k/EPIC arrays ignore CpGs which are "GC" in the forward strand?
# Why do Illumina 850k/EPIC arrays ignore CpGs which are "GC" in the forward strand?

(Asked by: username_0 on 2022-11-20)

CpGs are symmetrical, in that a CG sequence on the forward strand is hybridized to a GC --- and both dinucleotides on each opposing strand are CpGs dinucleotides which can be methylated. Conversely, CpGs can be GC on the forward strand but CG on the reverse strand.
FORWARD -> 5'--CG--3'  [OR]  5'--GC--3' <- FORWARD
REVERSE -> 3'--GC--5'        3'--CG--5' <- REVERSE

The assignment of "forward" and "reverse" strandedness is more or less arbitrary.
Given the above, why does it seem like the Illumina 850k (aka EPIC) array only profiles methylation from CpGs which are CG in the forward strand, while ignoring CpGs which are GC in the forward strand? I would also love to hear if my premises are wrong.
Here is some R code illustrating the issue at hand:
suppressPackageStartupMessages({
  library(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)
  library(tidyverse)})
data(IlluminaHumanMethylationEPICanno.ilm10b4.hg19)

IlluminaHumanMethylationEPICanno.ilm10b4.hg19 %>%
  getAnnotation() %>%
  as_tibble() %>%
  count(forward_seq=str_extract(Forward_Sequence, "\\[[ATCG]{2}\\]"))

# Results:
# # A tibble: 3 × 2
#   forward_seq      n
#           
# 1 [CA]          2922
# 2 [CG]        862927
# 3 [CT]            10
```

**Tags:** genome, database, sequence-annotation, genomics, public-databases
> **Comments:**
> **username_0**: I cross-posted this to Biostars: https://www.biostars.org/p/9545804/  

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## 1 answers

### Answer by username_0 on 2022-11-28. Score: 1 | Accepted answer

My question was kindly answered by Biostars user [Papyrus](https://www.biostars.org/p/9545804/#9545835), who pointed out that a GC in the 5' to 3' direction is a GpC dinucleotide, not a CpG dinucleotide. GpC dinucleotides are then biologically and chemically distinct from CpG dinucleotides, due to the directionality of the DNA polymer.


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