The reason to switch from a proportion (%, beta-value, whichever; anything
measuring M / (M+U) where M and U are surrogates for methylated and
unmethylated cytosines) to a fold-change (logit(proportion.methylated) or
log2(M/U)) is that the latter is far more amenable to linear models, and
roughly parallels the expected behavior in terms of expression changes on a
log2 or log-fold-change scale.
Furthermore, the range for logit(M/U) is -Infinity to +Infinity, which is
appropriate when you are modeling something as having Gaussian error.
Something with a range of 0 to 1 is neither homoskedastic (which is to
say, such a 0-1 measurement will have a variance that depends on the mean)
nor unbounded (this turns out to be an issue when computing maximum
likelihood estimates, for example, as values close to the boundary will
cause problems).
In any event, logit(% methylation) is equivalent to log(M/U) which is where
I veered off course this morning. My brain seems to have been a bit slow.
On Fri, Aug 17, 2012 at 9:26 AM, zeynep özkeserli <
zeynep.ozkeserli@gmail.com> wrote:
> Dear Tim,
>
> Thank you for your answer. But to my understanding, if I could get this
> answer by undoing the logit function (I tought you were doing this), we
> should use inverse logit function. Which is exp(x)/(1+exp(x))
>
> And in my case it gives:
>
> > exp(-0.30427)/(1+exp(-0.30427))
> [1] 0.424514
>
> Ok, this seems reasonable. And it makes sense how you put this into words.
> But if we could use this one as a methylation measure, why would the
> creators make things more complicated and convert the value to a logit
> value? So, again, to my understanding, I shall learn how to interpret the
> diff thing.
>
> Thank you again,
>
> Best :)
>
> Zeynep
>
> On Fri, Aug 17, 2012 at 6:29 PM, Tim Triche, Jr. wrote:
>
>> Perhaps "on average this region has an
>>
>> R> 1 - exp(-0.347)
>> [1] 0.2931947
>>
>> approximately 29.3% relative decrease in cytosine methylation after
>> treatment?"
>>
>>
>>
>> On Fri, Aug 17, 2012 at 1:56 AM, zeynep özkeserli <
>> zeynep.ozkeserli@gmail.com> wrote:
>>
>>> Dear All, Dear Dr. Aryee and Dr. Carvalho,
>>>
>>> I have a question on interpreting the results of dmrFinder function.
>>>
>>> We have performed a CHARM analysis on the data we got from NimbleGen
>>> Promoter Medip Arrays. The data is obtained from each patient before and
>>> after treatment. And after performing CHARM analysis, we got some
>>> differentially methylated regions (DMRs).
>>>
>>> As the samples are before and after treatment results of the same
>>> patient,
>>> the samples are treated as paired samples.
>>>
>>> My question is about interpretation of the results:
>>>
>>> After running this:
>>>
>>> dmr1_2 <- dmrFinder(rawData, p = p, groups = grp,compare = c("to", "ts"),
>>> cutoff=0.995,paired=TRUE,pairs=pairs)
>>>
>>> to: before treatment
>>> ts: after treatment
>>>
>>> - For example I have found a DMR like this (I summerized the result for
>>> my
>>> question):
>>>
>>> chr 8, diff= -0.30427 and maxdiff=0.47935
>>>
>>> As the diff value is calculated like this: average l (logit(percentage)
>>> methylation if l=NULL) difference within the DMR if paired=TRUE
>>>
>>> Is it true to say that: "The region has 0.30427 times the risk of being
>>> methylated in samples of after treatment compared to samples of before
>>> treatment."
>>>
>>> I know that it does not look meaningful to use the word "risk" when
>>> talking
>>> about something like that but I can not find a better way to say it
>>> truely. Is it possible to express it like a "0.30427 fold difference in
>>> methylation"? And also am I interpreting the "-" sign truely?
>>>
>>> Thank you for your help in advance,
>>>
>>> Best Regards,
>>>
>>> Zeynep
>>>
>>> [[alternative HTML version deleted]]
>>>
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>>>
>>
>>
>>
>> --
>> *A model is a lie that helps you see the truth.*
>> *
>> *
>> Howard Skipper
>>
>>
>
--
*A model is a lie that helps you see the truth.*
*
*
Howard Skipper
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