Harnessing Unsupervised Ensemble Learning for Biomedical Applications: A Review of Methods and Advances

Advancements in data availability and computational techniques, including machine learning, have transformed the field of bioinformatics, enabling the robust analysis of complex, high-dimensional, and heterogeneous biomedical data. This paper explores how diverse bioinformatics tasks, including differential expression analysis, network inference, and somatic mutation calling, can be reframed as binary classification tasks, thereby providing a unifying framework for their analysis. Traditional single-method approaches often fail to generalize across datasets due to differences in data distributions, noise levels, and underlying biological contexts. Ensemble learning, particularly unsupervised ensemble approaches, emerges as a compelling solution by integrating predictions from multiple algorithms to leverage their strengths and mitigate weaknesses. This review focuses on the principles and recent advancements in ensemble learning, with a particular emphasis on unsupervised ensemble methods. These approaches demonstrate their ability to address critical challenges in bioinformatics, such as the lack of labeled data and the integration of predictions from algorithms operating on different scales. Overall, this paper highlights the transformative potential of ensemble learning in advancing predictive accuracy, robustness, and interpretability across diverse bioinformatics applications.