Sihai Dave Zhao

Yaohua Rong, Sihai Dave Zhao, Xia Zheng et al.

Wide heterogeneity exists in cancer patients' survival, ranging from a few months to several decades. To accurately predict clinical outcomes, it is vital to build an accurate predictive model that relates patients' molecular profiles with patients' survival. With complex relationships between survival and high-dimensional molecular predictors, it is challenging to conduct non-parametric modeling and irrelevant predictors removing simultaneously. In this paper, we build a kernel Cox proportional hazards semi-parametric model and propose a novel regularized garrotized kernel machine (RegGKM) method to fit the model. We use the kernel machine method to describe the complex relationship between survival and predictors, while automatically removing irrelevant parametric and non-parametric predictors through a LASSO penalty. An efficient high-dimensional algorithm is developed for the proposed method. Comparison with other competing methods in simulation shows that the proposed method always has better predictive accuracy. We apply this method to analyze a multiple myeloma dataset and predict patients' death burden based on their gene expressions. Our results can help classify patients into groups with different death risks, facilitating treatment for better clinical outcomes.

Robin Tu, Alexander H. Foss, Sihai D. Zhao

Capturing patterns of variation present in a dataset is important in exploratory data analysis and unsupervised learning. Contrastive dimension reduction methods, such as contrastive principal component analysis (cPCA), find patterns unique to a target dataset of interest by contrasting with a carefully chosen background dataset representing unwanted or uninteresting variation. However, such methods typically require a tuning parameter that governs the level of contrast, and it is unclear how to choose this parameter objectively. Furthermore, it is frequently of interest to contrast against multiple backgrounds, which is difficult to accomplish with existing methods. We propose unique component analysis (UCA), a tuning-free method that identifies low-dimensional representations of a target dataset relative to one or more comparison datasets. It is computationally efficient even with large numbers of features. We show in several experiments that UCA with a single background dataset achieves similar results compared to cPCA with various tuning parameters, and that UCA with multiple individual background datasets is superior to both cPCA with any single background data and cPCA with a pooled background dataset.

Tao Yang, Paul Thompson, Sihai Zhao et al.

Genome-wide association studies (GWA studies or GWAS) investigate the relationships between genetic variants such as single-nucleotide polymorphisms (SNPs) and individual traits. Recently, incorporating biological priors together with machine learning methods in GWA studies has attracted increasing attention. However, in real-world, nucleotide-level bio-priors have not been well-studied to date. Alternatively, studies at gene-level, for example, protein--protein interactions and pathways, are more rigorous and legitimate, and it is potentially beneficial to utilize such gene-level priors in GWAS. In this paper, we proposed a novel two-level structured sparse model, called Sparse Group Lasso with Group-level Graph structure (SGLGG), for GWAS. It can be considered as a sparse group Lasso along with a group-level graph Lasso. Essentially, SGLGG penalizes the nucleotide-level sparsity as well as takes advantages of gene-level priors (both gene groups and networks), to identifying phenotype-associated risk SNPs. We employ the alternating direction method of multipliers algorithm to optimize the proposed model. Our experiments on the Alzheimer's Disease Neuroimaging Initiative whole genome sequence data and neuroimage data demonstrate the effectiveness of SGLGG. As a regression model, it is competitive to the state-of-the-arts sparse models; as a variable selection method, SGLGG is promising for identifying Alzheimer's disease-related risk SNPs.