RE: rare event

From: Ann Atzberger (Ann.Atzberger@EMBL-Heidelberg.de)
Date: Mon Dec 06 1999 - 05:44:02 EST


Guten Morgen Seamus,

An example:

Sample is stained with CD19/Fitc.So I collect 10,000 cells. On FSC v SSC
can see good distinction between RBC's, dead cells, lymphs and mono's. Set
a gate on the lymphs, look at FLi v FL2 with the gate on. There is a total
of 638 events in this profile, 632 events fall in the NEG quadrant and 6
events in the POS quadrant which are well separated.
So that is : 0.94% positives within the lymphocyte gate which equals 0.06
positives of the total population.

So what I think you're saying is that the 0.06% value is not accurate due
to the frequency distribution being below 50 cells. Could be, but was it
the issue??

What I'm saying is that if I split the sample in two and analyse both
fractions I get the same percentages for both fractions i.e good precision.
Which is what Hai Qi is not getting.

all the best
Ann




At 13:33 03.12.99 -0600, you wrote:
>
>Ann - -I am a little puzzled. The statistics of a 0.05% population in 10,000
>total cells is only 5 cells. Even with the best possible background, the
>confidence limits of that frequency are statistically pretty poor. In the
>paper I gave to Hai Qi (see corrected reference on Flow Cytometry Mailing
>List), we explored this issue and showed that accurate frequency prediction
>is relatively poor below about 20 cells and only really gets stable at about
>50 cells. If you see something that I don't, I would really want to know!
>--Jim Leary
>
>-----Original Message-----
>From: Ann Atzberger [mailto:Ann.Atzberger@EMBL-Heidelberg.de]
>Sent: Friday, December 03, 1999 7:32 AM
>To: cyto-inbox
>Subject: Re: rare event
>
>
>
>Hallo Hai Qi,
>
>if I understand correctly, you ran a total of 200 thousand cells of the
>same sample through the machine twice. As you say the subpopulation is not
>that rare at 0.15%.  I have often analysed samples with rare events at
>0.05% of the total population with good precision,(granted the signal was
>way above background) and only saving 10,000 events.
>
>If you have a lot of debris or dead cells in the sample the %s can vary; so
>you can either: 1.use a ficoll gradient to clean up the sample.
>2.reset your threshold value to cut out as much debris as possible.
>3.live gate.
>4.Run the cells slowly through the machine.
>5.Make sure the machine is clean, as bits of junk stuck in the sample probe
>can effect your values. 
>
>I might be wrong but I think saving 200,000 cells has to be more than ample
>to detect this subpopulation.
>
>Ann
>At 16:49 01.12.99 -0600, you wrote:
>>
>>
>>It is really not too rare, a cell population about 0.04% to 0.15%, while
>the
>>background is 0.01-0.05%. The problem is the variation among different
>>measurements, presumably due to the systematic error. For example, I had
>>10e7 total cells and ran 2*10e5 out of them for two times: one time I got
>>0.04% and the other time I got 0.15%. In order to have smaller variation,
>>obviously I have to increase my sample size, but the last thing I want to
>do
>>is to run through all 10e7 cells. Can anyone give me a handy statistical
>>method for estimating the sample size that makes a cost-effective
>>compromise? Thank you very much.
>>
>>Hai Qi
>>Dept. of Pathology, UTMB
>>
>>
>
>



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