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

Jinghui Li; Tianjing Zhao; Dailu Guan; Zhangyuan Pan; Zhonghao Bai; Jinyan Teng; Zhe Zhang; Zhili Zheng; Jian Zeng; Huaijun Zhou; Lingzhao Fang; Hao Cheng

doi:10.1016/j.xgen.2023.100390

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

Cell Genom. 2023 Aug 24;3(10):100390. doi: 10.1016/j.xgen.2023.100390. eCollection 2023 Oct 11.

Authors

Jinghui Li¹, Tianjing Zhao¹, Dailu Guan¹, Zhangyuan Pan¹, Zhonghao Bai², Jinyan Teng³, Zhe Zhang³, Zhili Zheng^{4

5}, Jian Zeng⁴, Huaijun Zhou¹, Lingzhao Fang², Hao Cheng¹

Affiliations

¹ Department of Animal Science, University of California, Davis, Davis, CA 95616, USA.
² Center for Quantitative Genetics and Genomics (QGG), Aarhus University, 8000 Aarhus, Denmark.
³ State Key Laboratory of Swine and Poultry Breeding Industry, National Engineering Research Center for Breeding Swine Industry, Guangdong Provincial Key Lab of Agro-Animal Genomics and Molecular Breeding, College of Animal Science, South China Agricultural University, Guangzhou 510642, China.
⁴ Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD 4072, Australia.
⁵ Program in Medical and Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA 02142, USA.

Abstract

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.

Keywords: complex trait; deep learning; functional conservation; gene expression; human; pig.