DESCRIPTION (Adapted from the Applicant's Abstract): Functional data are common
in cancer studies and other biomedical research, such as biomarkers measured
over time in cancer experiments and other clinical trials, growth curves,
hormone profiles, circadian rhythms in biological signals and drug activities.
Although much work has been done on functional models for independent data,
extensions to incorporate complex designs and correlations are still very
preliminary. The first specific aim of this application is to develop general
functional models using smoothing splines that can incorporate complex designs
and allow flexible nonparametric between-curve random effects. Another
long-existing problem for functional models is the heavy computational demand.
Except in very simple cases, most of the current estimation procedures need to
invert large dimensional matrices. This prevents applications to large data
sets. In this application, we will develop O(N) sequential estimation
procedures for general functional models by modifications of the Kalman
filtering and fixed interval smoothing.
Serial measurements have become a natural part of patient monitoring and
medical diagnosis. In monitoring and predicting a patient-specific outcome
based on laboratory tests or other biomarkers, we can obtain more accurate
predictions by borrowing the strength from the existing patient population
profiles over time. In medical diagnosis, we can gain efficiency by using the
up-to-date cumulative information and compare the individual profile with the
existing group profiles. In this application, we will develop dynamic patient
monitoring and diagnostic methods, in which flexible functional models will be
used to model both the population and individual profiles. With the proposed
sequential estimation procedures, these methods can be efficiently calculated
and implemented in a real time setting, which leads to rapid medical
interventions.
Most current statistical inference procedures rely on the distributional
assumptions, such as the normality assumption. When the distribution is
multimodal, it is often difficult to make parametric assumptions, and therefore
nonparametric density estimation methods are needed. In this application, we
will develop general density models and their associated inference procedures,
and apply these methods to accessible biomedical data sets.
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