Semiparametric models play important roles in the field of biological statistics. In this dissertation, two types of semiparametic models are to be studied. One is the partially linear model, where the parametric part is a linear function. We are to investigate the two common estimation methods for the partially linear models when the data is correlated — longitudinal or clustered. The other is a semiparametric model where a latent covariate is incorporated in a mixed effects model. We will propose a semiparametric approach for estimation of this model and apply it to the study on colon carcinogenesis. First, we study the profilekernel and backfitting methods in partially linear models for clustered/longitudinal data. For independent data, despite the potential rootn inconsistency of the backfitting estimator noted by Rice (1986), the two estimators have the same asymptotic variance matrix as shown by Opsomer and Ruppert (1999). In this work, theoretical comparisons of the two estimators for multivariate responses are investigated. We show that, for correlated data, backfitting often produces a larger asymptotic variance than the profilekernel method; that is, in addition to its bias problem, the backfitting estimator does not have the same asymptotic efficiency as the profilekernel estimator when data is correlated. Consequently, the common practice of using the backfitting method to compute profilekernel estimates is no longer advised. We illustrate this in detail by following Zeger and Diggle (1994), Lin and Carroll (2001) with a working independence covariance structure for nonparametric estimation and a correlated covariance structure for parametric estimation. Numerical performance of the two estimators is investigated through a simulation study. Their application to an ophthalmology dataset is also described. Next, we study a mixed effects model where the main response and covariate variables are linked through the positions where they are measured. But for technical reasons, they are not measured at the same positions. We propose a semiparametric approach for this misaligned measurements problem and derive the asymptotic properties of the semiparametric estimators under reasonable conditions. An application of the semiparametric method to a colon carcinogenesis study is provided. We find that, as compared with the corn oil supplemented diet, fish oil supplemented diet tends to inhibit the increment of bcl2 (oncogene) gene expression in rats when the amount of DNA damage increases, and thus promotes apoptosis.

In an experiment to understand colon carcinogenesis, all animals were exposed to a carcinogen while half the animals were also exposed to radiation. Spatially, we measured the existence of aberrant crypt foci (ACF), namely morphologically changed colonic crypts that are known to be precursors of colon cancer development. The biological question of interest is whether the locations of these ACFs are spatially correlated: if so, this indicates that damage to the colon due to carcinogens and radiation is localized. Statistically, the data take the form of binary outcomes (corresponding to the existence of an ACF) on a regular grid. We develop score??type methods based upon the Matern and conditionally autoregression (CAR) correlation models to test for the spatial correlation in such data, while allowing for nonstationarity. Because of a technical peculiarity of the score??type test, we also develop robust versions of the method. The methods are compared to a generalization of Moran??s test for continuous outcomes, and are shown via simulation to have the potential for increased power. When applied to our data, the methods indicate the existence of spatial correlation, and hence indicate localization of damage. Assuming that there are correlations in the locations of the ACF, the questions are how great are these correlations, and whether the correlation structures di?er when an animal is exposed to radiation. To understand the extent of the correlation, we cast the problem as a spatial binary regression, where binary responses arise from an underlying Gaussian latent process. We model these marginal probabilities of ACF semiparametrically, using ?xed-knot penalized regression splines and single-index models. We ?t the models using pairwise pseudolikelihood methods. Assuming that the underlying latent process is strongly mixing, known to be the case for many Gaussian processes, we prove asymptotic normality of the methods. The penalized regression splines have penalty parameters that must converge to zero asymptotically: we derive rates for these parameters that do and do not lead to an asymptotic bias, and we derive the optimal rate of convergence for them. Finally, we apply the methods to the data from our experiment.

In an experiment to understand colon carcinogenesis, all animals were exposed to a carcinogen while half the animals were also exposed to radiation. Spatially, we measured the existence of aberrant crypt foci (ACF), namely morphologically changed colonic crypts that are known to be precursors of colon cancer development. The biological question of interest is whether the locations of these ACFs are spatially correlated: if so, this indicates that damage to the colon due to carcinogens and radiation is localized. Statistically, the data take the form of binary outcomes (corresponding to the existence of an ACF) on a regular grid. We develop score??type methods based upon the Matern and conditionally autoregression (CAR) correlation models to test for the spatial correlation in such data, while allowing for nonstationarity. Because of a technical peculiarity of the score??type test, we also develop robust versions of the method. The methods are compared to a generalization of Moran??s test for continuous outcomes, and are shown via simulation to have the potential for increased power. When applied to our data, the methods indicate the existence of spatial correlation, and hence indicate localization of damage. Assuming that there are correlations in the locations of the ACF, the questions are how great are these correlations, and whether the correlation structures di?er when an animal is exposed to radiation. To understand the extent of the correlation, we cast the problem as a spatial binary regression, where binary responses arise from an underlying Gaussian latent process. We model these marginal probabilities of ACF semiparametrically, using ?xed-knot penalized regression splines and single-index models. We ?t the models using pairwise pseudolikelihood methods. Assuming that the underlying latent process is strongly mixing, known to be the case for many Gaussian processes, we prove asymptotic normality of the methods. The penalized regression splines have penalty parameters that must converge to zero asymptotically: we derive rates for these parameters that do and do not lead to an asymptotic bias, and we derive the optimal rate of convergence for them. Finally, we apply the methods to the data from our experiment.

Modeling of quantile curves is a common problem across various fields in today's practice. The topic of this thesis is estimating quantile curves in case of two-sample gradual change. That is, when a relationship between two continuous variables in two samples is of interest, where the relationship is the same for both samples until a certain value of the explanatory variable. From that point on the relationship can differ. The result of this thesis is a procedure for estimating quantile curves, which fulfill this concept. 1

Die Quantilsregression untersucht die Quantilfunktion QY |X (τ ), sodass ∀τ ∈ (0, 1), FY |X [QY |X (τ )] = τ erfu ̈llt ist, wobei FY |X die bedingte Verteilungsfunktion von Y gegeben X ist. Die Quantilsregression ermo ̈glicht eine genauere Betrachtung der bedingten Verteilung u ̈ber die bedingten Momente hinaus. Diese Technik ist in vielerlei Hinsicht nu ̈tzlich: beispielsweise fu ̈r das Risikomaß Value-at-Risk (VaR), welches nach dem Basler Akkord (2011) von allen Banken angegeben werden muss, fu ̈r ”Quantil treatment-effects” und die ”bedingte stochastische Dominanz (CSD)”, welches wirtschaftliche Konzepte zur Messung der Effektivit ̈at einer Regierungspoli- tik oder einer medizinischen Behandlung sind. Die Entwicklung eines Verfahrens zur Quantilsregression stellt jedoch eine gro ̈ßere Herausforderung dar, als die Regression zur Mitte. Allgemeine Regressionsprobleme und M-Scha ̈tzer erfordern einen versierten Umgang und es muss sich mit nicht- glatten Verlustfunktionen besch ̈aftigt werden. Kapitel 2 behandelt den Einsatz der Quantilsregression im empirischen Risikomanagement w ̈ahrend einer Finanzkrise. Kapitel 3 und 4 befassen sich mit dem Problem der h ̈oheren Dimensionalit ̈at und nichtparametrischen Techniken der Quantilsregression. / Quantile regression studies the conditional quantile function QY|X(τ) on X at level τ which satisfies FY |X QY |X (τ ) = τ , where FY |X is the conditional CDF of Y given X, ∀τ ∈ (0,1). Quantile regression allows for a closer inspection of the conditional distribution beyond the conditional moments. This technique is par- ticularly useful in, for example, the Value-at-Risk (VaR) which the Basel accords (2011) require all banks to report, or the ”quantile treatment effect” and ”condi- tional stochastic dominance (CSD)” which are economic concepts in measuring the effectiveness of a government policy or a medical treatment. Given its value of applicability, to develop the technique of quantile regression is, however, more challenging than mean regression. It is necessary to be adept with general regression problems and M-estimators; additionally one needs to deal with non-smooth loss functions. In this dissertation, chapter 2 is devoted to empirical risk management during financial crises using quantile regression. Chapter 3 and 4 address the issue of high-dimensionality and the nonparametric technique of quantile regression.