Hi Christian,

On Mar 10, 10:53 am, cstratowa <[email protected]
ingelheim.com> wrote:
> Dear all,
>
> I am currently determining copynumber regions for tumor cell lines
> using GLAD as model for the SNP6.0 array. (This takes about 13 hrs per
> array and per cluster node)

Despite GLAD being a good segmentation algorithm, you may want to
consider alternatives that are less computationally intensive and give
equivalent results. CBS (package DNAcopy in bioconductor) runs in 1.5h
for a SNP6.0 array. A fairly new but very promising program is
Ultrasome (http://www.broad.mit.edu/ultrasome). It segments a SNP6.0
array in 2 seconds (plus 1 minute to read the array). It's a
standalone program.

> My problem is the interpretation of the results.
> Here are some examples:
>
> 1. example:
> "chromosome"  "start"       "stop"        "mean"        "count"       "call"
> 1         3674045         10539859       0.154251128612596       4517   
> "neutral"
> 1         10544961        10544961       1.57871123504559        1      "gain"
> 1         10546623        10546623       -2.21390332082091       1      "loss"
> 1         10548849        21751915       0.150400582947561       6872   
> "neutral"
>
> This example has two regions where start=stop position (10544961,
> 10546623).
> How do you interpret this result?
> How should regions with count=1 be interpreted?
> Are these two regions considered to be outliers?

SNP6.0 arrays are very noisy. You should be very careful when you
consider any segment that has a size < 10 probes, and in any case, you
should not believe any segment that has a size of one probe. In your
case, I would just delete these segments. They are likely to be marked
as "outliers" by GLAD.

> 2. example:
> "chromosome"  "start"       "stop"        "mean"        "count"       "call"
> 6         18253390        18253886       -1.33576824261601       2      "loss"
> 6         18254264        29945167       -0.0986937482773974     7921   
> "neutral"
> 6         29945167        29945167       1.47894372023   1      "gain"
> 6         29945294        30015940       0.225347608366043       42     "gain"
>
> Here you see two regions with different start positions but identical
> stop positions (=29945167), where one region shows a gain but the
> other region is neutral.
> How do you interpret this result?

Same problem, count is too small.

> 3. example:
> "chromosome"  "start"       "stop"        "mean"        "count"       "call"
> 8         15672606        15672655       -2.45103201175721       2      "loss"
> 8         15672695        15672695       -4.68547262667068       1      "loss"
> 8         15672695        15678118       -2.65573944523429       10     "loss"
> 8         15678687        15678880       -2.01991964356680       3      "loss"
>
> In this case two regions have identical start positions (=15672695).
> How can this be the case?
> Could this be a bug, since it is assumed that two regions should not
> overlap?
>
> 4. example:
> "chromosome"  "start"       "stop"        "mean"        "count"       "call"
> 17        23813398        32995436       -0.272936124639797      5529   
> "neutral"
> 17        32999012        32999012       -2.26635873379834       1      "loss"
> 17        32999012        32999012       -8.28862000630996       1      "loss"
> 17        33000940        36676630       -0.295688057544771      1841   
> "neutral"
>
> This example seems to be a combination of examples 2 and 3:
> Here you have two identical regions with identical positions and
> start=stop (=32999012)
> How can two regions be identical but show a different mean (-2.266 vs
> -8.288)?
> Could this be a bug?

Probably a bug, but again, this region should be discarded.

> In summary my questions are:
> How should I interpret the results?
> Would it be better to eliminate these regions?
>
> Thank you in advance.
> Best regards
> Christian

Nicolas
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