Department of Pharmacology, University of Oxford; Mansfield Road, Oxford, United Kingdom.
Department of Physiology, Anatomy and Genetics, University of Oxford; Parks Road, United Kingdom.
PLoS Comput Biol. 2024 Jan 17;20(1):e1011793. doi: 10.1371/journal.pcbi.1011793. eCollection 2024 Jan.
Electrophysiological recordings from freely behaving animals are a widespread and powerful mode of investigation in sleep research. These recordings generate large amounts of data that require sleep stage annotation (polysomnography), in which the data is parcellated according to three vigilance states: awake, rapid eye movement (REM) sleep, and non-REM (NREM) sleep. Manual and current computational annotation methods ignore intermediate states because the classification features become ambiguous, even though intermediate states contain important information regarding vigilance state dynamics. To address this problem, we have developed "Somnotate"-a probabilistic classifier based on a combination of linear discriminant analysis (LDA) with a hidden Markov model (HMM). First we demonstrate that Somnotate sets new standards in polysomnography, exhibiting annotation accuracies that exceed human experts on mouse electrophysiological data, remarkable robustness to errors in the training data, compatibility with different recording configurations, and an ability to maintain high accuracy during experimental interventions. However, the key feature of Somnotate is that it quantifies and reports the certainty of its annotations. We leverage this feature to reveal that many intermediate vigilance states cluster around state transitions, whereas others correspond to failed attempts to transition. This enables us to show for the first time that the success rates of different types of transition are differentially affected by experimental manipulations and can explain previously observed sleep patterns. Somnotate is open-source and has the potential to both facilitate the study of sleep stage transitions and offer new insights into the mechanisms underlying sleep-wake dynamics.
在睡眠研究中,对自由活动动物进行电生理记录是一种广泛而强大的研究模式。这些记录产生了大量的数据,需要进行睡眠分期注释(多导睡眠图),即将数据根据三种警觉状态进行划分:清醒、快速眼动(REM)睡眠和非快速眼动(NREM)睡眠。手动和当前的计算注释方法忽略了中间状态,因为分类特征变得模糊不清,尽管中间状态包含有关警觉状态动态的重要信息。为了解决这个问题,我们开发了“Somnotate”-一种基于线性判别分析(LDA)与隐马尔可夫模型(HMM)相结合的概率分类器。首先,我们证明 Somnotate 在多导睡眠图中设定了新标准,在对小鼠电生理数据的注释准确性方面超过了人类专家,对训练数据中的错误具有出色的鲁棒性,与不同的记录配置兼容,并且在实验干预期间能够保持高精度。然而,Somnotate 的关键特点是它量化并报告其注释的确定性。我们利用这一特点揭示了许多中间警觉状态围绕着状态转换聚集,而其他状态则对应于状态转换的失败尝试。这使我们能够首次表明,不同类型的转换的成功率受到实验操作的不同影响,并解释了之前观察到的睡眠模式。Somnotate 是开源的,有可能既促进睡眠分期转换的研究,又为睡眠-觉醒动态的机制提供新的见解。