Hong Zhang

Hong Zhang
Merck & Co. | MSD

Doctor of Philosophy

About

16
Publications
940
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42
Citations
Introduction

Publications

Publications (16)
Article
Full-text available
In pharmacogenetic (PGx) studies, drug response phenotypes are often measured in the form of change in a quantitative trait before and after treatment. There is some debate in recent literature regarding baseline adjustment, or inclusion of pre-treatment or baseline value as a covariate, in PGx genome-wide association studies (GWAS) analysis. Here,...
Article
Analyzing correlated data by goodness-of-fit type tests is a critical statistical problem in many applications. A unified framework is provided through a general family of goodness-of-fit tests (GGOF) to address this problem. The GGOF family covers many classic and newly developed tests, such as the minimal p-value test, Simes test, the GATES, one-...
Article
Combining dependent tests of significance has broad applications but the related p‐value calculation is challenging. For Fisher's combination test, current p‐value calculation methods (e.g., Brown's approximation) tend to inflate the type I error rate when the desired significance level is substantially less than 0.05. The problem could lead to sig...
Article
We evaluated the impact of class I and class II human leukocyte antigen (HLA) genotypes, heterozygosity, and diversity on the efficacy of pembrolizumab. Seventeen pembrolizumab clinical trials across eight tumor types and one basket trial in patients with advanced solid tumors were included (n > 3,500 analyzed). Germline DNA was genotyped using a c...
Article
In computational and applied statistics, it is of great interest to get fast and accurate calculation for the distributions of the quadratic forms of Gaussian random variables. This paper presents a novel approximation strategy that contains two developments. First, we propose a fast numerical procedure in computing the moments of the quadratic for...
Article
Non-proportional hazards data are routinely encountered in randomized clinical trials. In such cases, classic Cox proportional hazards model can suffer from severe power loss, with difficulty in interpretation of the estimated hazard ratio since the treatment effect varies over time. We propose CauchyCP, an omnibus test of change-point Cox regressi...
Preprint
Full-text available
Non-proportional hazards data are routinely encountered in randomized clinical trials. In such cases, classic Cox proportional hazards model can suffer from severe power loss, with difficulty in interpretation of the estimated hazard ratio since the treatment effect varies over time. We propose CauchyCP, an omnibus test of change-point Cox regressi...
Article
Full-text available
Integrating association evidence across multiple traits can improve the power of gene discovery and reveal pleiotropy. Most multi-trait analysis methods focus on individual common variants in genome-wide association studies. Here, we introduce multi-trait analysis of rare-variant associations (MTAR), a framework for joint analysis of association su...
Preprint
Fast and accurate calculation for the distributions of Quadratic forms of centered Gaussian variables is of interest in computational statistics. This paper presents a novel numerical procedure to efficiently compute the moments of a given quadratic form. Based on that, a gamma distribution with matched skewness-kurtosis ratio is proposed to approx...
Preprint
Combining dependent tests of significance has broad applications but the $p$-value calculation is challenging. Current moment-matching methods (e.g., Brown's approximation) for Fisher's combination test tend to significantly inflate the type I error rate at the level less than 0.05. It could lead to significant false discoveries in big data analyse...
Article
It is of substantial interest to discover novel genetic markers that influence drug response in order to develop personalized treatment strategies that maximize therapeutic efficacy and safety. To help enable such discoveries, we focus on testing the association between the cumulative effect of multiple single nucleotide polymorphisms (SNPs) in a p...
Article
Full-text available
Wolbachia is a bacterium that is present in 60% of insects but it is not generally found in Aedes aegypti, the primary vector responsible for the transmission of dengue virus, Zika virus, and other human diseases caused by RNA viruses. Wolbachia has been shown to stop the growth of a variety of RNA viruses in Drosophila and in mosquitoes. Wolbachia...
Preprint
This paper concerns the problem of applying the generalized goodness-of-fit (gGOF) type tests for analyzing correlated data. The gGOF family broadly covers the maximum-based testing procedures by ordered input $p$-values, such as the false discovery rate procedure, the Kolmogorov-Smirnov type statistics, the $\phi$-divergence family, etc. Data anal...
Article
Full-text available
For testing a group of hypotheses, tremendous $p$-value combination methods have been developed and widely applied since 1930's. Some methods (e.g., the minimal $p$-value) are optimal for sparse signals, and some others (e.g., Fisher's combination) are optimal for dense signals. To address a wide spectrum of signal patterns, this paper proposes a u...
Article
Full-text available
In big data analysis for detecting rare and weak signals among $n$ features, some grouping-test methods such as Higher Criticism test (HC), Berk-Jones test (B-J), and $\phi$-divergence test share the similar asymptotical optimality when $n \rightarrow \infty$. However, in practical data analysis $n$ is frequently small and moderately large at most....