MOTIVATION: Data normalization is an important step in processing proteomics data generated in mass spectrometry experiments, which aims to reduce sample-level variation and facilitate comparisons of samples. Previously published methods for normalization primarily depend on the assumption that the distribution of protein expression is similar across all samples. However, this assumption fails when the protein expression data is generated from heterogenous samples, such as from various tissue types. This led us to develop a novel data-driven method for improved normalization to correct the systematic bias meanwhile maintaining underlying biological heterogeneity. RESULTS: To robustly correct the systematic bias, we used the density-power-weight method to down-weigh outliers and extended the one-dimensional robust fitting method described in the previous work to our structured data. We then constructed a robustness criterion and developed a new normalization algorithm, called RobNorm.In simulation studies and analysis of real data from the genotype-tissue expression project, we compared and evaluated the performance of RobNorm against other normalization methods. We found that the RobNorm approach exhibits the greatest reduction in systematic bias while maintaining across-tissue variation, especially for datasets from highly heterogeneous samples. AVAILABILITYAND IMPLEMENTATION: https://github.com/mwgrassgreen/RobNorm. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Accurately detecting tissue specificity (TS) in genes helps researchers understand tissue functions at the molecular level. The Genotype-Tissue Expression project is one of the publicly available data resources, providing large-scale gene expressions across multiple tissue types. Multiple tissue comparisons and heterogeneous tissue expression make it challenging to accurately identify tissue specific gene expression. How to distinguish the inlier expression from the outlier expression becomes important to build the population level information and further quantify the TS. There still lacks a robust and data-adaptive TS method taking into account heterogeneities of the data. RESULTS: We found that the key to identify tissue specific gene expression is to properly define a concept of expression population. In a linear regression problem, we developed a novel data-adaptive robust estimation approach (AdaReg) based on density-power-weight under unknown outlier distribution and non-vanishing outlier proportion. The Gaussian-population mixture model was considered in the setting of identifying TS. We took into account heterogeneities of gene expression and applied the robust data-adaptive procedure to estimate the population parameters. With the well-estimated population parameters, we constructed the AdaTiSS algorithm.Our AdaTiSS profiled TS for each gene and each tissue, which standardized the gene expression in terms of TS. We provided a new robust and powerful tool to the literature of defining TS. AVAILABILITY AND IMPLEMENTATION: https://github.com/mwgrassgreen/AdaTiSS. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Privacy concern in data sharing especially for health data gains particularly increasing attention nowadays. Now some patients agree to open their information for research use, which gives rise to a new question of how to effectively use the public information to better understand the private dataset without breaching privacy. In this paper, we specialize this question as selecting an optimal subset of the public dataset for M-estimators in the framework of differential privacy (DP) in [1]. From a perspective of non-interactive learning, we first construct the weighted private density estimation from the hybrid datasets under DP. Along the same line as [2], we analyze the accuracy of the DP M-estimators based on the hybrid datasets. Our main contributions are (i) we find that the bias-variance tradeoff in the performance of our M-estimators can be characterized in the sample size of the released dataset; (2) based on this finding, we develop an algorithm to select the optimal subset of the public dataset to release under DP. Our simulation studies and application to the real datasets confirm our findings and set a guideline in the real application.

MOTIVATION: Inappropriate disclosure of human genomes may put the privacy of study subjects and of their family members at risk. Existing privacy-preserving mechanisms for Genome-Wide Association Studies (GWAS) mainly focus on protecting individual information in case-control studies. Protecting privacy in family-based studies is more difficult. The transmission disequilibrium test (TDT) is a powerful family-based association test employed in many rare disease studies. It gathers information about families (most frequently involving parents, affected children and their siblings). It is important to develop privacy-preserving approaches to disclose TDT statistics with a guarantee that the risk of family 're-identification' stays below a pre-specified risk threshold. 'Re-identification' in this context means that an attacker can infer that the presence of a family in a study. METHODS: In the context of protecting family-level privacy, we developed and evaluated a suite of differentially private (DP) mechanisms for TDT. They include Laplace mechanisms based on the TDT test statistic, P-values, projected P-values and exponential mechanisms based on the TDT test statistic and the shortest Hamming distance (SHD) score. RESULTS: Using simulation studies with a small cohort and a large one, we showed that that the exponential mechanism based on the SHD score preserves the highest utility and privacy among all proposed DP methods. We provide a guideline on applying our DP TDT in a real dataset in analyzing Kawasaki disease with 187 families and 906 SNPs. There are some limitations, including: (1) the performance of our implementation is slow for real-time results generation and (2) handling missing data is still challenging. AVAILABILITY AND IMPLEMENTATION: The software dpTDT is available in https://github.com/mwgrassgreen/dpTDT. CONTACT: [email protected]. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.