Addressing sex bias in biological databases worldwide

Precision medicine aims at tailoring treatments to individual patient needs. In this context, artificial intelligence (AI)-based technologies are viewed as revolutionary since they have the capacity to identify key features that link genomic and phenotypic traits at the individual level. AI techniques therefore depend on the quantity and quality of patient data. When variables like sex, age, or race are ignored in sample records, it can result in biased predictions as they will not be considered in the training of the AI algorithm. To this end, the European Genome-phenome Archive (EGA) took action in 2018 and put into place a rule that requires data providers to declare the sex of donor samples uploaded into their repository to improve data quality and prevent the spread of biased results. In this work we quantified biases in sex classification over time in human data from studies deposited in EGA and the database of Genotypes and Phenotypes (dbGaP), which represents the EGA's equivalent in the USA. The main result is that the EGA policy is effective to fight sex classification biases because there are significantly less samples classified as unknown after 2018 in this repository than in dbGaP. Additionally, we qualitatively assessed public opinion on this issue. A survey addressed to users, creators, maintainers, and developers of biological databases revealed that specialized training and additional knowledge about diversity criteria are required. Based on our findings, we raise awareness of sample bias problems and provide a list of recommendations for enhancing biomedical research practices.