Eid, Fatma-ElzahraaElmarakeby, Haitham A.Chan, Yujia AlinaFornelos, NadineElHefnawi, MahmoudVan Allen, Eliezer M.Heath, Lenwood S.Lage, Kasper2021-05-192021-05-192021-02-10183http://hdl.handle.net/10919/103378Biases in data used to train machine learning (ML) models can inflate their prediction performance and confound our understanding of how and what they learn. Although biases are common in biological data, systematic auditing of ML models to identify and eliminate these biases is not a common practice when applying ML in the life sciences. Here we devise a systematic, principled, and general approach to audit ML models in the life sciences. We use this auditing framework to examine biases in three ML applications of therapeutic interest and identify unrecognized biases that hinder the ML process and result in substantially reduced model performance on new datasets. Ultimately, we show that ML models tend to learn primarily from data biases when there is insufficient signal in the data to learn from. We provide detailed protocols, guidelines, and examples of code to enable tailoring of the auditing framework to other biomedical applications. Fatma-Elzahraa Eid et al. illustrate a principled approach for identifying biases that can inflate the performance of biological machine learning models. When applied to three biomedical prediction problems, they identify previously unrecognized biases and ultimately show that models are likely to learn primarily from data biases when there is insufficient learnable signal in the data.application/pdfenCreative Commons Attribution 4.0 InternationalArticle - Refereedhttps://doi.org/10.1038/s42003-021-01674-541335687412399-3642