Deep convolutional and conditional neural networks for large-scale genomic data generation
Authors: Yelmen Burak , Decelle Aurélien , Boulos Leila Lea , Szatkownik Antoine , Furtlehner Cyril , Charpiat Guillaume , Jay Flora 
Published: March 2023

Applications of generative models for genomic data have gained significant momentum in the past few years, with scopes ranging from data characterization to generation of genomic segments and functional sequences. In our previous study, we demonstrated that generative adversarial networks (GANs) and restricted Boltzmann machines (RBMs) can be used to create novel high-quality artificial genomes (AGs) which can preserve the complex characteristics of real genomes such as population structure, linkage disequilibrium and selection signals. However, a major drawback of these models is scalability, since the large feature space of genome-wide data increases computational complexity vastly. To address this issue, we implemented a novel convolutional Wasserstein GAN (WGAN) model along with a novel conditional RBM (CRBM) framework for generating AGs with high SNP number. These networks implicitly learn the varying landscape of haplotypic structure in order to capture complex correlation patterns along the genome and generate a wide diversity of plausible haplotypes. We performed comparative analyses to assess both the quality of these generated haplotypes and the amount of possible privacy leakage from the training data.

As the importance of genetic privacy becomes more prevalent, the need for effective privacy protection measures for genomic data increases. We used generative neural networks to create large artificial genome segments which possess many characteristics of real genomes without substantial privacy leakage from the training dataset. In the near future with further improvements in haplotype quality and privacy preservation, large-scale artificial genome databases can be assembled to provide easily accessible surrogates of real databases, allowing researchers to conduct studies with diverse genomic data within a safe ethical framework in terms of donor privacy.

Author summary

Generative modelling has recently become a prominent research field in genomics, with applications ranging from functional sequence design to characterization of population structure. We previously used generative neural networks to create artificial genome segments which possess many characteristics of real genomes but these segments were short in size due to computational requirements. In this work, we present novel generative models for generating artificial genomes with larger sequence size. We test the generated artificial genomes with multiple summary statistics to assess the haplotype quality, overfitting and privacy leakage from the training dataset. Our findings suggest that although there is still room for improvement both in terms of genome quality and privacy preservation, convolutional architectures and conditional generation can be utilised for generating good quality, large-scale genomic data. In the near future with additional improvements, large-scale artificial genomes can be used for assembling surrogate biobanks as alternatives to real biobanks with access restrictions, increasing data accessibility to researchers around the globe.