All clocks but GrimAge report the same age

[fjuradorueda]

Hi guys! Thanks for developing this tool, it is very useful!

My team and I have used this tool on our methylation data before. However, I encountered a problem with our last data, the epigenetic age of all subjects was the same across all clocks but GrimAge. I am running out of ideas of what to do:

-I relaunched the tool on previous idats files and works perfectly
-I took a look at the beta values of these subjects and look just fine. I computed and plotted the PCAs and the distribution and R2 look normal
-I have launched on subsets of the population and still encounter the problem. Even with a subset of just 3 subjects

Thanks you in advance for any possible idea on what to do
Best! Fran

[albertchen42]

Hi, thank you! I'm not immediately sure what the issue is without looking at your data. It sounds like it is imputing all CpGs based on the reference dataset rather than using your dataset, which would suggest to me there is an issue with the CpG variable names or file format. By the way, the PC clocks have also been incorporated into this package: https://github.com/HigginsChenLab/methylCIPHER. We will be updating this moving forward.

…

On Fri, Apr 4, 2025 at 5:43 AM fjuradorueda ***@***.***> wrote: Hi guys! Thanks for elaborating on this tool, it is very useful! My team and I have used this tool on our methylation data before. However, I encountered a problem with our last data, the epigenetic age of all subjects was the same across all clocks but GrimAge. I am running out of ideas of what to do: -I relaunched the tool on previous idats files and works perfectly -I took a look at the beta values of these subjects and look just fine. I computed and plotted the PCAs and the distribution and R2 look normal - I have launched on subsets of the population and still encounter the problem. Even with a subset of just 3 subjects Thanks you in advance for any possible idea on what to do Best! Fran — Reply to this email directly, view it on GitHub <#13>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AB6AXA74YTBX7GPSAHR5V3T2XZH5RAVCNFSM6AAAAAB2OJP4I2VHI2DSMVQWIX3LMV43ASLTON2WKOZSHE3TCOBTGEYTGNA> . You are receiving this because you are subscribed to this thread.Message ID: ***@***.***> [image: fjuradorueda]*fjuradorueda* created an issue (MorganLevineLab/PC-Clocks#13) <#13> Hi guys! Thanks for elaborating on this tool, it is very useful! My team and I have used this tool on our methylation data before. However, I encountered a problem with our last data, the epigenetic age of all subjects was the same across all clocks but GrimAge. I am running out of ideas of what to do: -I relaunched the tool on previous idats files and works perfectly -I took a look at the beta values of these subjects and look just fine. I computed and plotted the PCAs and the distribution and R2 look normal - I have launched on subsets of the population and still encounter the problem. Even with a subset of just 3 subjects Thanks you in advance for any possible idea on what to do Best! Fran — Reply to this email directly, view it on GitHub <#13>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AB6AXA74YTBX7GPSAHR5V3T2XZH5RAVCNFSM6AAAAAB2OJP4I2VHI2DSMVQWIX3LMV43ASLTON2WKOZSHE3TCOBTGEYTGNA> . You are receiving this because you are subscribed to this thread.Message ID: ***@***.***>

[Camerashots]

Hi, thank you! I'm not immediately sure what the issue is without looking
at your data. It sounds like it is imputing all CpGs based on the reference
dataset rather than using your dataset, which would suggest to me there is
an issue with the CpG variable names or file format. By the way, the PC
clocks have also been incorporated into this package:
https://github.com/HigginsChenLab/methylCIPHER. We will be updating this
moving forward.
…

Dear Albert and the whole team,

thank you so much for developing this amazing and helpful package!

Maybe an unrelated question (and please delete it if you think it doesn't belong here), but I could not raise an issue at the methylCIPHER page. When I try to initiate the calcPCClocks function from methylCIPHER
analysis <-methylCIPHER::calcPCClocks(t(as.matrix(data)),anno) ,
I get the following message:
Enter '1' to start a new auth process or select a pre-authorized account.
1: Send me to the browser for a new auth process.

As I login, however, I see the following message a the required file is not downloaded.

PCClocks Data does not exist in package directory. Downloading data...
Error in `drive_download()`:
  ! Download failed.

I was able to circumvent this by manually downloading the required file from this page into my HOME environment, but might be interesting in the future to take a look at this.

Hope this helps to anyone!

Best,
Matej

[albertchen42]

Apologies, we are actually currently updating the methylCIPHER package this week to solve this issue! I will also ensure that that issues can be raised on the updated package.

[albertchen42]

We have updated the methylCIPHER package to allow calculation of PC clocks and SystemsAge, including downloading the files using a dedicated download_methylCIPHER function: https://github.com/HigginsChenLab/methylCIPHER.

[Camerashots]

We have updated the methylCIPHER package to allow calculation of PC clocks and SystemsAge, including downloading the files using a dedicated download_methylCIPHER function: https://github.com/HigginsChenLab/methylCIPHER.

Hi Albert,

Thank you very much for your quick response and hard work! The function works now as expected!

During the use I found the formatting of the pheno dataframe a bit tricky to get right at first. I would find really helpful if there was a guideline for formatting it to the required format.

Best regards and thanks again,
Matej