This book presents an overview of recent developments in biostatistics and bioinformatics. Written by active researchers in these emerging areas, it is intended to give graduate students and new researchers an idea of where the frontiers of biostatistics and bioinformatics are as well as a forum to learn common techniques in use, so that they can advance the fields via developing new techniques and new results. Extensive references are provided so that researchers can follow the threads to learn more comprehensively what the literature is and to conduct their own research. In particulars, the book covers three important and rapidly advancing topics in biostatistics: analysis of survival and longitudinal data, statistical methods for epidemiology, and bioinformatics.

Estimation of genewise variance arises from two important applications in microarray data analysis: selecting significantly differentially expressed genes and validation tests for normalization of microarray data. We approach the problem by introducing a two-way nonparametric model, which is an extension of the famous Neyman-Scott model and is applicable beyond microarray data. The problem itself poses interesting challenges because the number of nuisance parameters is proportional to the sample size and it is not obvious how the variance function can be estimated when measurements are correlated. In such a high-dimensional nonparametric problem, we proposed two novel nonparametric estimators for genewise variance function and semiparametric estimators for measurement correlation, via solving a system of nonlinear equations. Their asymptotic normality is established. The finite sample property is

It has been reported that the plasma levels of VEGF in tumor patients decreased during dendritic cell (DC)-based immunotherapy, but the underlying mechanism remains unclear. Our current report demonstrates that VEGF levels were significantly decreased in the supernatants of DCs incubated with rhVEGF or tumor conditioned medium (TCM) while the intracellular VEGF in DCs was increased. The increased intracellular VEGF was not due to the <i>de novo</i> VEGF synthesis by DCs because exogenous VEGF inhibited the mRNA expression of VEGF in DCs. More direct evidence was provided to demonstrate that Cy3-labeled VEGF could be internalized by DCs specifically and efficiently. In addition, the activity of DCs to internalize VEGF was abolished by neutralizing antibody against VEGF receptor-1 (Flt-1) and inhibitors of endocytosis such as carbonyl cyanide m-chlorophenyl hydrazone (CCCP) and genistein. This

In an event-related functional MRI data analysis, an accurate and robust extraction of the hemodynamic response function (HRF) and its associated statistics (e.g., magnitude, width, and time to peak) is critical to infer quantitative information about the relative timing of the neuronal events in different brain regions. The aim of this paper is to develop a multiscale adaptive smoothing model (MASM) to accurately estimate HRFs pertaining to each stimulus sequence across all voxels. MASM explicitly accounts for both spatial and temporal smoothness information, while incorporating such information to adaptively estimate HRFs in the frequency domain. One simulation study and a real data set are used to demonstrate the methodology and examine its finite sample performance in HRF estimation, which confirms that MASM significantly outperforms the existing methods including the smooth finite impulse

Large-scale multiple testing with correlated and heavy-tailed data arises in a wide range of research areas from genomics, medical imaging to finance. Conventional methods for estimating the false discovery proportion (FDP) often ignore the effect of heavy-tailedness and the dependence structure among test statistics, and thus may lead to inefficient or even inconsistent estimation. Also, the assumption of joint normality is often imposed, which is too stringent for many applications. To address these challenges, in this paper we propose a factoradjusted robust procedure for large-scale simultaneous inference with control of the false discovery proportion. We demonstrate that robust factor adjustments are extremely important in both improving the power of the tests and controlling FDP. We identify general conditions under which the proposed method produces consistent estimate of the FDP. As a byproduct that is of independent interest, we establish an exponential-type deviation inequality for a robust U-type covariance estimator under the spectral norm. Extensive numerical experiments demonstrate the advantage of the proposed method over several state-of-the-art methods especially when the data are generated from heavy-tailed distributions. Our proposed procedures are implemented in the R-package FarmTest. Supported by NSF Grants DMS-1662139, DMS-1712591, and NIH Grant R01-GM072611-12.