Department of Computer Science, ETH Zurich, Zürich, Switzerland.
Max Planck Institute for Intelligent Systems, Tübingen, Germany.
PLoS Comput Biol. 2019 Apr 18;15(4):e1006968. doi: 10.1371/journal.pcbi.1006968. eCollection 2019 Apr.
Understanding sleep and its perturbation by environment, mutation, or medication remains a central problem in biomedical research. Its examination in animal models rests on brain state analysis via classification of electroencephalographic (EEG) signatures. Traditionally, these states are classified by trained human experts by visual inspection of raw EEG recordings, which is a laborious task prone to inter-individual variability. Recently, machine learning approaches have been developed to automate this process, but their generalization capabilities are often insufficient, especially across animals from different experimental studies. To address this challenge, we crafted a convolutional neural network-based architecture to produce domain invariant predictions, and furthermore integrated a hidden Markov model to constrain state dynamics based upon known sleep physiology. Our method, which we named SPINDLE (Sleep Phase Identification with Neural networks for Domain-invariant LEearning) was validated using data of four animal cohorts from three independent sleep labs, and achieved average agreement rates of 99%, 98%, 93%, and 97% with scorings from five human experts from different labs, essentially duplicating human capability. It generalized across different genetic mutants, surgery procedures, recording setups and even different species, far exceeding state-of-the-art solutions that we tested in parallel on this task. Moreover, we show that these scored data can be processed for downstream analyzes identical to those from human-scored data, in particular by demonstrating the ability to detect mutation-induced sleep alteration. We provide to the scientific community free usage of SPINDLE and benchmarking datasets as an online server at https://sleeplearning.ethz.ch. Our aim is to catalyze high-throughput and well-standardized experimental studies in order to improve our understanding of sleep.
理解睡眠及其受环境、突变或药物的干扰仍然是生物医学研究的一个核心问题。在动物模型中,通过对脑电图 (EEG) 特征的分类来检查睡眠。传统上,这些状态是通过对原始 EEG 记录的人工专家进行分类来进行分类的,这是一项费力的任务,容易受到个体间差异的影响。最近,已经开发了机器学习方法来自动化这个过程,但它们的泛化能力往往不足,尤其是在来自不同实验研究的动物之间。为了解决这个挑战,我们制作了一个基于卷积神经网络的架构,以产生领域不变的预测,并且进一步集成了一个隐马尔可夫模型,以根据已知的睡眠生理学来约束状态动态。我们的方法,我们称之为 SPINDLE(使用神经网络进行领域不变学习的睡眠阶段识别),使用来自三个独立睡眠实验室的四个动物队列的数据进行了验证,并达到了与来自不同实验室的五名人类专家评分的 99%、98%、93%和 97%的平均一致性率,基本上复制了人类的能力。它在不同的遗传突变体、手术程序、记录设置甚至不同的物种中具有通用性,远远超过了我们在该任务上并行测试的最新解决方案。此外,我们表明,这些评分数据可以进行下游分析,与来自人类评分数据的分析完全相同,特别是通过证明检测突变诱导的睡眠改变的能力。我们将 SPINDLE 和基准数据集免费提供给科学界使用,并作为在线服务器在 https://sleeplearning.ethz.ch 上提供。我们的目标是促进高通量和标准化的实验研究,以提高我们对睡眠的理解。