[BioC] Detection Above Background (DABG) on Gene Level for Exon and Gene Arrays

cstrato cstrato at aon.at
Tue Sep 21 23:18:34 CEST 2010


Dear Pascal,

Dut to the design of xps it is not only able to support DABG calls at 
both the probeset and transcript level, but does also support MAS5 
detection calls for both Exon 1.0 ST and Gene 1.0 ST Arrays.

To answer your question whether DABG is valid on the transcript level I 
think you need to distinguish between HuExon and HuGene arrays:

For HuExon arrays the statement of Affymetrix is probably true for genes 
where alternative splicing occurs. However, HuGene arrays were 
originally designed by Affymetrix as arrays measuring the transcript 
level and thus I assume they have tried to select mainly probes which 
are not affected by alternative splicing, so the statement may not apply.

I would also be interested to hear from user experiences not only with 
DABG on the transcript level but also with MAS5 calls on Exon ST and 
Gene ST arrays. In my own experience the p-values between DABG and MAS5 
calls are almost identical for very low p-values but partly tend to 
differ for larger p-values.

Best regards
Christian
_._._._._._._._._._._._._._._._._._
C.h.r.i.s.t.i.a.n   S.t.r.a.t.o.w.a
V.i.e.n.n.a           A.u.s.t.r.i.a
e.m.a.i.l:        cstrato at aon.at
_._._._._._._._._._._._._._._._._._


On 9/21/10 2:27 PM, Pascal Gellert wrote:
> Hi all,
>
> The detection above background algorithm calculates a p-value for each
> probe set, indication if this probe set is expressed or not (within the
> background noise).
> This is similar to the MAS5 detection calls, but Exon 1.0 ST and Gene
> 1.0 ST Arrays don't have mismatch probes, therefore MAS5 cannot be used.
>
> According to Affymetrix, the DABG is not valid on gene level:
>
> "There is a strong assumption in DABG
> that all the probes are measuring the same
> thing (i.e., the same transcript). This is not
> the case at the gene level due to alternative
> splicing. For example, probes for a cassette
> exon that is skipped will contribute to a mis-
> leadingly insignificant p-value."
>
> To obtain, if a gene is expressed, often all probe sets of a gene were
> used. If less than e.g. 50% of the exons of the gene are above a DABG
> threshold, the gene is considered as not expressed.
>
> Nevertheless, the XPS package supports DABG on gene level. Does anyone
> has experiences with DAGB on gene level?
>
> Thanks,
>
> Pascal Gellert
>
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