Feature selection is an indispensable step for the analysis of high-dimensional molecular data. Despite its importance, consensus is lacking on how to choose the most appropriate feature selection methods, especially when the performance of the feature selection methods itself depends on hyper-parameters. Bayesian optimization has demonstrated its advantages in automatically configuring the settings of hyper-parameters for various models. However, it remains unclear whether Bayesian optimization can benefit feature selection methods. In this research, we conducted extensive simulation studies to compare the performance of various feature selection methods, with a particular focus on the impact of Bayesian optimization on those where hyper-parameters tuning is needed. We further utilized the gene expression data obtained from the Alzheimer's Disease Neuroimaging Initiative to predict various brain imaging-related phenotypes, where various feature selection methods were employed to mine the data. We found through simulation studies that feature selection methods with hyper-parameters tuned using Bayesian optimization often yield better recall rates, and the analysis of transcriptomic data further revealed that Bayesian optimization-guided feature selection can improve the accuracy of disease risk prediction models. In conclusion, Bayesian optimization can facilitate feature selection methods when hyper-parameter tuning is needed and has the potential to substantially benefit downstream tasks.

The detection of Parkinson’s disease (PD) in its early stages is of great importance for its treatment and management, but consensus is lacking on what information is necessary and what models should be used to best predict PD risk. In our study, we first grouped PD-associated factors based on their cost and accessibility, and then gradually incorporated them into risk predictions, which were built using eight commonly used machine learning models to allow for comprehensive assessment. Finally, the Shapley Additive Explanations (SHAP) method was used to investigate the contributions of each factor. We found that models built with demographic variables, hospital admission examinations, clinical assessment, and polygenic risk score achieved the best prediction performance, and the inclusion of invasive biomarkers could not further enhance its accuracy. Among the eight machine learning models considered, penalized logistic regression and XGBoost were the most accurate algorithms for assessing PD risk, with penalized logistic regression achieving an area under the curve of 0.94 and a Brier score of 0.08. Olfactory function and polygenic risk scores were the most important predictors for PD risk. Our research has offered a practical framework for PD risk assessment, where necessary information and efficient machine learning tools were highlighted.

Building an accurate disease risk prediction model is an essential step in the modern quest for precision medicine. While high-dimensional genomic data provides valuable data resources for the investigations of disease risk, their huge amount of noise and complex relationships between predictors and outcomes have brought tremendous analytical challenges. Deep learning model is the state-of-the-art methods for many prediction tasks, and it is a promising framework for the analysis of genomic data. However, deep learning models generally suffer from the curse of dimensionality and the lack of biological interpretability, both of which have greatly limited their applications. In this work, we have developed a deep neural network (DNN) based prediction modeling framework. We first proposed a group-wise feature importance score for feature selection, where genes harboring genetic variants with both linear and non-linear effects are efficiently detected. We then designed an explainable transfer-learning based DNN method, which can directly incorporate information from feature selection and accurately capture complex predictive effects. The proposed DNN-framework is biologically interpretable, as it is built based on the selected predictive genes. It is also computationally efficient and can be applied to genome-wide data. Through extensive simulations and real data analyses, we have demonstrated that our proposed method can not only efficiently detect predictive features, but also accurately predict disease risk, as compared to many existing methods.

The use of human genome discoveries and other established factors to build an accurate risk prediction model is an essential step toward precision medicine. While multi-layer high-dimensional omics data provide unprecedented data resources for prediction studies, their corresponding analytical methods are much less developed. We present a multi-kernel penalized linear mixed model with adaptive lasso (MKpLMM), a predictive modeling framework that extends the standard linear mixed models widely used in genomic risk prediction, for multi-omics data analysis. MKpLMM can capture not only the predictive effects from each layer of omics data but also their interactions via using multiple kernel functions. It adopts a data-driven approach to select predictive regions as well as predictive layers of omics data, and achieves robust selection performance. Through extensive simulation studies, the analyses of PET-imaging outcomes from the Alzheimer’s Disease Neuroimaging Initiative study, and the analyses of 64 drug responses, we demonstrate that MKpLMM consistently outperforms competing methods in phenotype prediction. The R-package is available at https://github.com/YaluWen/OmicPred. Supplementary data are available at Bioinformatics online.

Motivation: DNA methylation is an important epigenetic modification that has essential role in gene regulation, cell differentiation, and cancer development. Bisulfite sequencing is a widely used technique to obtain genome-wide DNA methylation profiles, and one of the key tasks of analyzing bisulfite sequencing data is to detect differentially methylated regions (DMRs) among samples under different treatment conditions. Although numerous tools have been proposed to detect differentially methylated single CpG site (DMC) between samples, methods for direct DMR detection, especially for complex study designs, are largely limited.