Biomedical Engineering Reference
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one variable plotted against the other. The same situation is true for our cytometry
data. The actual lineage lines for B cells can be quite puzzling when one tries to
trace them in some of the two-parameter histograms. These same relations are
normally very simple when presented as parameter profiles in a probability state
model.
14.11 THE FUTURE OF CYTOMETRIC ANALYSIS
At the outset, I wanted to convince you that this method represents the future of
cytometry analysis. We have discussed how it solves the dimensionality barrier and
how it accounts for population overlap. Once a progression-specific scaffold is
defined by a set of common parameters, any number of tubes can be analyzed and
added to the model. There is no limit to the number of parameters that can be
examined in this manner. The final output is a graph that merges intensity patterns,
percentages, and population variances in an understandable format.
These advantages over conventional techniques are just the beginning of what is
possible. These advantages will ultimately move cytometry from being gate-based to
model-based, but the paradigm change is likely to be a slow process if these were the
only advantages. The reason for the slow acceptance is that we have conventional
systems in place that are working and there will be a reluctance to fix these if they are
not perceived as broken.
14.11.1 Automation
What we have not discussed yet is the real power of themodel-based analysis system-
automation. We are living in a time where we are becoming more and more resource
limited, especially in the area of medical diagnostics. There is going to be increasing
pressure to develop low-cost, high-speed screening systems. These systems will need
to be robust and accurate.
The modeling system described in this chapter allows us to engineer model
systems that have attributes not attainable with gate-based systems. Each control
definition point that defines the parameter profiles can have a defined relation with any
other control definition point. We now have the means to create models that represent
normalcy where abnormal events are either excluded or captured by additional cell
types. These systems can be engineered to be completely automatic.
Initially, these automated systems will handle relatively simple tests, but over time,
more and more complex models will become available through the Internet and will
allow laboratories to achieve a higher degree of standardization than has been possible
so far.
While these automated systems take hold, scientists will use the models as a means
to better understand how biological systems work. The models will allow them to
concretely define what they think is going on in the cell and test new assumptions.
These models can be used to synthesize data sets and therefore be predictive. The art
of cytometry will slowly evolve to the science of cytometry.
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