Re: very rare events: how low can you go?

From: mandy cromwell (mandy_cromwell@hms.harvard.edu)
Date: Tue Jan 30 2001 - 12:58:50 EST


Lynn,

We have also been looking into this in the context of both
low-frequency MHC tetramer-binding and peptide-stimulated
intracellular cytokine staining events. I've come to the conclusion
that positive events occurring at frequencies as low as 0.05%, and
probably lower, can be statistically significant if: 1) you have a
negative control with sufficiently low background staining (0.01%)
and 2) you have collected a large enough number of events (this
example would require collection of 100,000  gated events from both
the negative control and the test sample).  We routinely collect
50,000 CD8+ lymphocyte events for MHC class I tetramers, which in
most cases allows us to detect <0.1% staining (if the background is
low enough). This was arrived at by doing a Chi-square analysis of
background events vs. test events.

I would also be interested to hear about other ways of determining
the minimum number of events needed to achieve significance. In his
intracellular cytokine staining talk at the Methods in Cytokine
Biology symposium, Calman Prussin mentioned the importance of
collecting large numbers of events and including multiple
controls-perhaps he would be willing to expand on those comments?

Thanks for posting the symposium announcement on the list, Calman,
and for organizing the event- it was a very worthwhile day.

Mandy

~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~~
Mandy Cromwell, Ph.D.
New England Regional Primate Research Center
Department of Immunology
Harvard Medical School
One Pine Hill Drive
Southborough, MA 01772
(508)624-8022





>Hello all,
>
>This question arises from a rather heated discussion following a seminar
>yesterday, in which the speaker claimed that flow cytometry is not
>useful for analyzing cells that are less than 1-2% of the starting
>population. I am sure that with all of the sorting, multicolor analysis,
>and multiparameter gating that people do, we can prove this assertion
>wrong.
>
>If you have experience or publications with analysis of events well
>below 1% of the starting cell population, could you please share some
>examples or references?
>
>Thanks in advance for your help!
>**********************************************
>Lynn B. Dustin, Ph.D.
>Center for the Study of Hepatitis C
>Rockefeller University
>Box 64
>1230  York Ave.
>New York, New York 10021
>Phone: 212-327-7067
>email: dustinl@mail.rockefeller.edu

Mandy



This archive was generated by hypermail 2b29 : Wed Apr 03 2002 - 11:57:20 EST