PT  - JOURNAL ARTICLE
AU  - Ruochi Zhang
AU  - Jianzhu Ma
AU  - Jian Ma
TI  - DANGO: Predicting higher-order genetic interactions
AID  - 10.1101/2020.11.26.400739
DP  - 2020 Jan 01
TA  - bioRxiv
PG  - 2020.11.26.400739
4099  - http://biorxiv.org/content/early/2020/11/27/2020.11.26.400739.short
4100  - http://biorxiv.org/content/early/2020/11/27/2020.11.26.400739.full
AB  - Higher-order genetic interactions, which have profound impact on phenotypic variations, remain poorly characterized. Almost all studies to date have primarily reported pairwise interactions because it is dauntingly difficult to design high-throughput genetic screenings of the large combinatorial search space for higher-order interactions. Here, we develop an algorithm named Dango, based on a self-attention hypergraph neural network, to effectively predict the higher-order genetic interaction for a group of genes. As a proof-of-concept, we make comprehensive prediction of >400 million trigenic interactions in the yeast S. cerevisiae, significantly expanding the quantitative characterization of trigenic interactions. We find that Dango can accurately predict trigenic interactions that reveal both known and new biological functions related to cell growth. The predicted trigenic interactions can also serve as powerful genetic markers to predict growth response to many distinct conditions. Dango enables unveiling a more complete map of complex genetic interactions that impinge upon phenotypic diversity.Competing Interest StatementThe authors have declared no competing interest.