Here are a sample of results obtained in this research program during the past year: Researchers often collect multivariate binary response data to compare naturally ordered experimental conditions. Some examples of ordered experimental conditions include doses in a dose-response study, cancer stages in clinical oncology, and time points in a time-course experiment. For example, the National Toxicology Program routinely conducts dose response studies to evaluate toxicity and carcinogenicity of chemicals. Typically, for each organ within each animal in the study, they record the presence and absence of tumor. Thus on each animal they obtain multivariate binary response vector where some of the components are potentially dependent. For example, mammary gland and pituitary gland tumors are known to be correlated. In such situations statistical methods that ignore the underlying dependence structure, and analyze one binary response at a time, can potentially be underpowered. In this research program we are developing multivariate statistical methods that take into account the underlying dependence structure when comparing experimental conditions. Specifically, we are developing methods for testing multivariate stochastic order among ordered experimental conditions. The new methods are not only more powerful than some of the existing methods, but they also provide biologically interpretable results. Increasingly researchers are interested in comparing a large number of variables between two or more experimental conditions. For example, a toxicologist may be interested in comparing the expressions of several thousands of genes between a normal and a tumor tissue, which results in performing thousands of statistical tests (known as multiple testing). A major concern when performing multiple tests is the control of overall false positive rate. Typically, the proportion of true null hypotheses among all null hypotheses is an unknown parameter and it plays an important role when developing statistical tests for multiple testing problems. Adaptive procedures have been proposed in the literature (Hochberg and Benjamini (1990)) that estimate the proportion of true nulls and use those estimates to derive powerful multiple testing procedures. Until now there did not exist a mathematical proof to demonstrate that these procedures control the familywise error rate (FWER) in general. In this project we introduced new adaptive Holm and Hochberg procedures and prove that they control the FWER under positive regression dependence.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Weiss, Sophie; Xu, Zhenjiang Zech; Peddada, Shyamal et al. (2017) Normalization and microbial differential abundance strategies depend upon data characteristics. Microbiome 5:27
Kaul, Abhishek; Davidov, Ori; Peddada, Shyamal D (2017) Structural zeros in high-dimensional data with applications to microbiome studies. Biostatistics :
Mandal, Siddhartha; Godfrey, Keith M; McDonald, Daniel et al. (2016) Fat and vitamin intakes during pregnancy have stronger relations with a pro-inflammatory maternal microbiota than does carbohydrate intake. Microbiome 4:55
Larriba, Yolanda; Rueda, Cristina; Fernández, Miguel A et al. (2016) Order restricted inference for oscillatory systems for detecting rhythmic signals. Nucleic Acids Res 44:e163
Rueda, Cristina; Fernández, Miguel A; Barragán, Sandra et al. (2016) Circular piecewise regression with applications to cell-cycle data. Biometrics 72:1266-1274
Grandhi, Anjana; Guo, Wenge; Peddada, Shyamal D (2016) A multiple testing procedure for multi-dimensional pairwise comparisons with application to gene expression studies. BMC Bioinformatics 17:104
Zhao, Haibing; Peddada, Shyamal D; Cui, Xinping (2015) Mixed directional false discovery rate control in multiple pairwise comparisons using weighted p-values. Biom J 57:144-58
Mandal, Siddhartha; Van Treuren, Will; White, Richard A et al. (2015) Analysis of composition of microbiomes: a novel method for studying microbial composition. Microb Ecol Health Dis 26:27663
Barragán, Sandra; Rueda, Cristina; Fernández, Miguel A et al. (2015) Determination of Temporal Order among the Components of an Oscillatory System. PLoS One 10:e0124842
Wu, Michael C; Joubert, Bonnie R; Kuan, Pei-fen et al. (2014) A systematic assessment of normalization approaches for the Infinium 450K methylation platform. Epigenetics 9:318-29

Showing the most recent 10 out of 26 publications