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

From: Houston, Jim (Jim.Houston@stjude.org)
Date: Tue Jan 30 2001 - 09:38:15 EST


This is a good topic for discussion.

What is the definition of rare?  1/100000 ?  1/1,000,000?

Those of us doing CD34 enumeration are routinely asked to give results
sometimes as low as .1%.  In fact normal adults have a measurable percentage
as low as .02%.  When I first started CD34 enumeration 5 years ago I was
told you had to have at least 50 of these positive events to be significant.
Needless to say we acquire alot of data to get these numbers.

20 years ago I believed the error  by flow to be around 2-5%.  If you run
the same tube 10 times you will get some variance in the percentage you are
looking for, particularly in the levels of .1%.  The problem occurring is
the significance of an increase from a measured .2% to a .4% level.  Is this
increase real or is it a factor of the instrument.  When this number is used
to calculate Absolute numbers in a leukopheresis product then it can be
significant.

Now I have been requested to give numbers lower than .01%.  How to make this
accurate?  Good question.  I assume that most populations have some inherent
properties to them.  They scatter light in discrete patterns and have some
sort of phenotype unique to them.  The more parameters I use the better the
confidence level.  If I set all analysis markers by isotype controls then
that could make my decision easier, but these give erroneous results if you
look at the data carefully.  If you collect 500,000 cells and then see a
population of 16 are these real????

In practice the low %'s <1% are at best sometimes subjective to the
operator's experience.

A good question is not only the ability by flow to give these low %'s but
how reproducible is it.  Some labs are running their samples in doublets or
triplets then averaging.  This will drive the cost up a bit.

Are there any statisticians out there who can answer some of these
questions?

Jim Houston

-----Original Message-----
From: Lynn Dustin [mailto:dustinl@mail.rockefeller.edu]
Sent: Friday, January 26, 2001 12:39 PM
To: cyto-inbox
Subject: very rare events: how low can you go?



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



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