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

Nat Commun. 2024 May 1;15(1):3685. doi: 10.1038/s41467-024-48005-w.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Behavior, Animal* / physiology
  • Drosophila Proteins / genetics
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster* / genetics
  • Drosophila melanogaster* / physiology
  • Locomotion* / genetics
  • Locomotion* / physiology
  • Male
  • Sleep* / genetics
  • Sleep* / physiology
  • Social Behavior

Substances

  • Drosophila Proteins