Epigenetics:Week3-Clincial Epigenetics by Emma Dempster https://padlet.com/eldempster1/tavs8709eup868xl Please use this board to post your comments on this weeks journal club papers, any questions or comments on this weeks content, or to post any resources you find that may be useful to the other students en-us 2021-01-21 18:06:06 UTC 2025-11-27 16:49:47 UTC hello@padlet.com eldempster1 https://padlet.com/eldempster1/tavs8709eup868xl/wish/1111316177 I have chosen this paper on classifying tumour types bases on cell-free DNA methylomes - I must admit I was hoping to select a more recent applied paper but on reading a few I thought the inferences were a little weak.

This is a Nature paper so quite heavy going and there are a lot of new methods and statistical techniques and simulations but the take-home message is that there appear to be distinct tumour-specific  DNA methylomes that can be detected in cell-free circulating DNA. The next challenge is to develop sensitive and specific assays before we can see this type of biomarker routinely used in the clinic.

A few pointers to think about when reading the paper:

Why was the gold standard whole-genome bisulfite sequencing not used?
What was the point of comparing the cfMedDip seq to the hybrid-capture mutation sequencing?
How comparable are the two different methylome sequencing technologies MeDip-seq and RRBS?
Why is the bisulfite-free approach a benefit when investigating tumour methylomes?

]]> 2021-01-21 18:09:46 UTC https://padlet.com/eldempster1/tavs8709eup868xl/wish/1111316177 New paper on classifying Sarcomas with DNA methylation profiling eldempster1 https://padlet.com/eldempster1/tavs8709eup868xl/wish/1118761993 2021-01-24 13:41:34 UTC https://padlet.com/eldempster1/tavs8709eup868xl/wish/1118761993 eldempster1 https://padlet.com/eldempster1/tavs8709eup868xl/wish/1126022155 2021-01-26 10:36:57 UTC https://padlet.com/eldempster1/tavs8709eup868xl/wish/1126022155 https://padlet.com/eldempster1/tavs8709eup868xl/wish/1198463993 Why was the gold standard whole-genome bisulfite sequencing not used?
They did attempt using WGBS, however this approach was high cost and inefficient for circulating cell-free DNA as DNA degraded during bisulfite conversion leading to limited information recovered for CpGs.

What was the point of comparing the cfMedDip seq to the hybrid-capture mutation sequencing?
cfMeDIP–seq was efficient between observed and expected numbers for  differentially methylated regions with low percentage of  false discovery rate, while hybrid capture mutation sequencing, detected mutations inefficiently. This highlights the excellent  sensitivity of cfMeDIP–seq for the detection of cancer-derived DNA. Furthermore, cfMeDIP–seq can enrich CpG-rich, enhancing cost-effectiveness and more information would be recovered by increasing initial DNA input.

How comparable are the two different methylome sequencing technologies  MeDip-seq and RRBS?
MeDip-seq is genome purification technique to enrich methylated DNA sequences, using 5-methylcytosine antibody. Whereas, RRBS uses restriction enzymes digestion and enrich high CpG regions using bisulfite sequencing. 

Why is the bisulfite-free approach a benefit when investigating tumour methylomes?
They were able to find hypermethylated regions in tumour tissue through circulating tumor DNA which could be a  non-invasive characterization of active transcription-factor networks in cancer using cfMeDIP–seq. Investigating tumour methylomes enables tumour classification and distinguishes patients with early-stage of pancreatic cancer from healthy controls using plasma cfDNA.

 
Thank you,
Nayra Al-Thani

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