Large-language models facilitate discovery of the molecular signatures regulating sleep and activity

Di Peng, Liubin Zheng, Dan Liu, Cheng Han, Xin Wang, Yan Yang, Li Song, Miaoying Zhao, Yanfeng Wei, Jiayi Li, Xiaoxue Ye, Yuxiang Wei, Zihao Feng, Xinhe Huang, Miaomiao Chen, Yujie Gou, Yu Xue () and Luoying Zhang ()
Additional contact information
Di Peng: Huazhong University of Science and Technology
Liubin Zheng: Huazhong University of Science and Technology
Dan Liu: Huazhong University of Science and Technology
Cheng Han: Huazhong University of Science and Technology
Xin Wang: Huazhong University of Science and Technology
Yan Yang: Huazhong University of Science and Technology
Li Song: Huazhong University of Science and Technology
Miaoying Zhao: Huazhong University of Science and Technology
Yanfeng Wei: Huazhong University of Science and Technology
Jiayi Li: Huazhong University of Science and Technology
Xiaoxue Ye: Huazhong University of Science and Technology
Yuxiang Wei: Huazhong University of Science and Technology
Zihao Feng: Huazhong University of Science and Technology
Xinhe Huang: Huazhong University of Science and Technology
Miaomiao Chen: Huazhong University of Science and Technology
Yujie Gou: Huazhong University of Science and Technology
Yu Xue: Huazhong University of Science and Technology
Luoying Zhang: Huazhong University of Science and Technology

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract Sleep, locomotor and social activities are essential animal behaviors, but their reciprocal relationships and underlying mechanisms remain poorly understood. Here, we elicit information from a cutting-edge large-language model (LLM), generative pre-trained transformer (GPT) 3.5, which interprets 10.2–13.8% of Drosophila genes known to regulate the 3 behaviors. We develop an instrument for simultaneous video tracking of multiple moving objects, and conduct a genome-wide screen. We have identified 758 fly genes that regulate sleep and activities, including mre11 which regulates sleep only in the presence of conspecifics, and NELF-B which regulates sleep regardless of whether conspecifics are present. Based on LLM-reasoning, an educated signal web is modeled for understanding of potential relationships between its components, presenting comprehensive molecular signatures that control sleep, locomotor and social activities. This LLM-aided strategy may also be helpful for addressing other complex scientific questions.

Date: 2024
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DOI: 10.1038/s41467-024-48005-w

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