Hi Sunny,

Thanks for your email and clarification. I am familiar with the term "null
hypothesis" from statistical perspective (although I am not trained as a
statistician), what I meant to clarify is exactly what is the null. I agree
with the caution of using p-value as a measure of the degree of differential
expression, but that's kinda off the topic. What I really meant to ask is
that for the two genes A and B, are they differentially expressed due to
true biological reason or technical reason.

Anyway, thanks for your effort on this, much appreciated.

-Jack

On Fri, Sep 24, 2010 at 2:22 PM, Sunny Srivastava
<research.baba@gmail.com>wrote:

> Hello Jack,
> I am sorry for writing a statistical statement without knowing your
> background.
>
> When I say "null", I mean the null hypothesis (it is just a statement that
> you reject using p-values) for the expression of a gene (A or B in your
> case). A null hypothesis is a status quo statement about the expression of
> any gene. In your case this is equivalent to saying that the gene (A or B)
> is not differentially expressed when you compare a person with disease to a
> healthy person. And you reject the null (hypothesis) if p-value is < 0.01.
>
> But most importantly, magnitude of p-values should not be used as an
> indicator for the strength of signal or indicator for the strength of
> differential expression of a gene in diseased compared to a healthy person.
> This can lead to wrong conclusions about a gene A being "more"
> differentially expressed than gene B (as you say: gene A is more significant
> than gene B if pvalue for A < pvalue for B when comparing diseased and
> healthy individuals), which may not be true. This is what I called
> 'trouble'.
>
> sorry for the statistical jargons.
>
> Thanks,
> S.
>
> On Fri, Sep 24, 2010 at 8:46 AM, Jack Luo <jluo.rhelp@gmail.com> wrote:
>
>> Sunny,
>>
>> What I meant by "p-value in the disease group is much more significant" is
>> that the detection call p-value in the disease group are more significant
>> than healthy group, which means the signal in the disease group is more
>> significantly above background noise than healthy group.
>>
>> I am not sure I understand what you mean by "the null", you mean the
>> background (or the mismatch probes)? When you say "strength of evidence", do
>> you mean the strength of the signal? Could you be more specific on what
>> "trouble" means?
>>
>> Sorry that I get lost here,
>>
>> -Jack
>>
>>
>> On Thu, Sep 23, 2010 at 5:43 PM, Sunny Srivastava <
>> research.baba@gmail.com> wrote:
>>
>>> Hello Jack,
>>> I am not sure what you mean by:
>>>
>>> "....p-value in the disease group is much more significant
>>> (say, 1e-10))."
>>>
>>> If you mean to use the *magnitude* of p-values as an indicator for the
>>> *strength* of evidence against (or for) the null, then it it can lead to
>>> trouble ... Theoretically speaking, it is incorrect to compare two p-values
>>> and make conclusions about the strength of evidence against (or for) the
>>> null (in your case *more* differential expression of Gene A in Disease
>>> compared to Control ).
>>>
>>> Thanks and Best Regards,
>>> S.
>>>
>>> On Thu, Sep 23, 2010 at 4:45 PM, Jack Luo <jluo.rhelp@gmail.com> wrote:
>>>
>>>> Hi,
>>>>
>>>> This is a conceptual question related to microarray, instead of the
>>>> usage of
>>>> any Bioconductor package. I apologize if this bothers anyone.
>>>>
>>>> I am struggling to understand the concept of differential expression in
>>>> terms of its resources (whether it is technical or biological). Suppose
>>>> I
>>>> have an experiment with two groups (healthy vs. disease) and try to find
>>>> some differentially expressed genes, take two genes for example, both of
>>>> them are differentially expressed (DE) between healthy and disease.
>>>>
>>>> Gene A has present detection call for all the samples under study (but
>>>> the
>>>> detection call p-value in the healthy group is in the order of 1e-2 ~
>>>> 1e-3,
>>>> the detection call p-value in the disease group is much more significant
>>>> (say, 1e-10)).
>>>> Gene B has 50% present call in healthy while 100% present call in
>>>> cancer.
>>>>
>>>> My question is what's the correct interpretation in terms of whether the
>>>> differential expression is due to technical or biological? Are they both
>>>> DE
>>>> due to technical, or A is DE due to biological and B is due to
>>>> technical, or
>>>> they are both DE due to biological?
>>>>
>>>> Thanks a bunch,
>>>>
>>>> -Jack
>>>>
>>>>        [[alternative HTML version deleted]]
>>>>
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>>>>
>>>
>>>
>>
>

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