Longitudinal omics data analysis: approaches and applications.

Longitudinal omics data (LOD) analysis is essential for understanding the dynamics of biological processes and disease progression over time. This review explores various statistical and computational approaches for analyzing such data, emphasizing their applications and limitations. The main characteristics of longitudinal data, such as imbalance, high-dimensionality, and non-Gaussianity are discussed for modeling and hypothesis testing. We discuss the properties of linear mixed models (LMM) and generalized linear mixed models (GLMM) as foundational tools in LOD analyses and highlight their extensions to handle the obstacles in the frequentist and Bayesian frameworks. We differentiate dynamic data analysis between time-course and longitudinal analyses, covering functional data analysis (FDA) and replication constraints. We explore classification techniques, single-cell studies as exemplary omics longitudinal studies, survival modeling, and multivariate methods for clinical/biomarker-based applications. Emerging topics, including data integration, clustering, and network-based modeling, are also discussed. We categorize the state-of-the-art approaches applicable to omics data, highlighting how they address the data features. This review serves as a guideline for researchers seeking robust strategies to analyze LOD effectively, which is usually complex.