Learning functional conservation between human and pig to decipher evolutionary mechanisms underlying gene expression and complex traits

• Published in: Cell genomics 2023-10, Vol.3 (10), p.100390, Article 100390
• Main Authors: Li, Jinghui, Zhao, Tianjing, Guan, Dailu, Pan, Zhangyuan, Bai, Zhonghao, Teng, Jinyan, Zhang, Zhe, Zheng, Zhili, Zeng, Jian, Zhou, Huaijun, Fang, Lingzhao, Cheng, Hao
• Format: Article
• Language: English
• Subjects: complex trait; deep learning; functional conservation; gene expression; human; pig
• ISSN: 2666-979X; 2666-979X
• DOI: 10.1016/j.xgen.2023.100390

Assessment of genomic conservation between humans and pigs at the functional level can improve the potential of pigs as a human biomedical model. To address this, we developed a deep learning-based approach to learn the genomic conservation at the functional level (DeepGCF) between species by integrating 386 and 374 functional profiles from humans and pigs, respectively. DeepGCF demonstrated better prediction performance compared with the previous method. In addition, the resulting DeepGCF score captures the functional conservation between humans and pigs by examining chromatin states, sequence ontologies, and regulatory variants. We identified a core set of genomic regions as functionally conserved that plays key roles in gene regulation and is enriched for the heritability of complex traits and diseases in humans. Our results highlight the importance of cross-species functional comparison in illustrating the genetic and evolutionary basis of complex phenotypes. [Display omitted] •DeepGCF improves the prediction accuracy of functional conservation•Sequence conservation shows a U-shaped relationship with functional conservation•Functionally conserved regions play key roles in regulatory activities•Functionally conserved regions show heritability enrichment in human complex traits Li et al. developed a deep learning model, DeepGCF, to learn the genomic conservation at the functional level between human and pig using epigenome and gene expression profiles. They identified a core set of regions as functionally conserved that plays key roles in gene regulation and complex traits in humans.