Genome data are crucial in modern medicine, offering significant potential for diagnosis and treatment. Thanks to technological advancements, many millions of healthy and diseased genomes have already been sequenced; however, obtaining the most suitable data for a specific study, and specifically for validation studies, remains challenging with respect to scale and access. Therefore, in silico genomics sequence generators have been proposed as a possible solution. However, the current generators produce inferior data using mostly shallow (stochastic) connections, detected with limited computational complexity in the training data. This means they do not take the appropriate biological relations and constraints, that originally caused the observed connections, into consideration. To address this issue, we propose cancer-inspired genomics mapper model (CGMM), that combines genetic algorithm (GA) and deep learning (DL) methods to tackle this challenge. CGMM mimics processes that generate genetic variations and mutations to transform readily available control genomes into genomes with the desired phenotypes. We demonstrate that CGMM can generate synthetic genomes of selected phenotypes such as ancestry and cancer that are indistinguishable from real genomes of such phenotypes, based on unsupervised clustering. Our results show that CGMM outperforms four current state-of-the-art genomics generators on two different tasks, suggesting that CGMM will be suitable for a wide range of purposes in genomic medicine, especially for much-needed validation studies.
Bibliographical noteFunding Information:
The authors wish to thank Olga Chervova, Vitaly Voloshin, Ismail Moghul, and Stephan Beck for their help in this project. This research received no specific grant from funding agencies in the public, commercial, or not-for-profit sectors.
© 2023 Elsevier Ltd
- Bioinformatics deep learning model
- Biomarker detection
- In silico genome generation