Open Access

Florian Lerch, Alfred Ultsch, Jörn Lötsch

• Finding subgroups in biomedical data is a key task in biomedical research and precision medicine. Already one-dimensional data, such as many different readouts from cell experiments, preclinical or human laboratory experiments or clinical signs, often reveal a more complex distribution than a single mode. Gaussian mixtures play an important role in the multimodal distribution of one-dimensional data. However, although fitting of Gaussian mixture models (GMM) is often aimed at obtaining the separate modes composing the mixture, current technical implementations, often using the Expectation Maximization (EM) algorithm, are not optimized for this task. This occasionally results in poorly separated modes that are unsuitable for determining a distinguishable group structure in the data. Here, we introduce “Distribution Optimization” an evolutionary algorithm to GMM fitting that uses an adjustable error function that is based on chi-square statistics and the probability density. The algorithm can be directly targeted at the separation of the modes of the mixture by employing additional criterion for the degree by which single modes overlap. The obtained GMM fits were comparable with those obtained with classical EM based fits, except for data sets where the EM algorithm produced unsatisfactory results with overlapping Gaussian modes. There, the proposed algorithm successfully separated the modes, providing a basis for meaningful group separation while fitting the data satisfactorily. Through its optimization toward mode separation, the evolutionary algorithm proofed particularly suitable basis for group separation in multimodally distributed data, outperforming alternative EM based methods.