Hearing loss is a major health problem and psychological burden in humans. Mouse models offer a possibility to elucidate genes involved in the underlying developmental and pathophysiological mechanisms of hearing impairment. To this end, large-scale mouse phenotyping programs include auditory phenotyping of single-gene knockout mouse lines. Using the auditory brainstem response (ABR) procedure, the German Mouse Clinic and similar facilities worldwide have produced large, uniform data sets of averaged ABR raw data of mutant and wildtype mice. In the course of standard ABR analysis, hearing thresholds are assessed visually by trained staff from series of signal curves of increasing sound pressure level. This is time-consuming and prone to be biased by the reader as well as the graphical display quality and scale. In an attempt to reduce workload and improve quality and reproducibility, we developed and compared two methods for automated hearing threshold identification from averaged ABR raw data: a supervised approach involving two combined neural networks trained on human-generated labels and a self-supervised approach, which exploits the signal power spectrum and combines random forest sound level estimation with a piece-wise curve fitting algorithm for threshold finding. We show that both models work well, outperform human threshold detection, and are suitable for fast, reliable, and unbiased hearing threshold detection and quality control. In a high-throughput mouse phenotyping environment, both methods perform well as part of an automated end-to-end screening pipeline to detect candidate genes for hearing involvement. Code for both models as well as data used for this work are freely available.
翻译:鼠标模型提供了一种可能性,以阐明在听力受损的基本发育和病理学机制中所涉及的基因。为此,大型鼠标口腔方案包括单基因击倒鼠标线的听觉小写写,目的是减少工作量,提高质量和可复制性。我们开发了两种从普通听力脑响应(ABR)程序、德国鼠诊所和全世界类似设施生成了大型统一的数据组,其中含有变种和野型小鼠的平均ABR原始数据。在标准ABR分析过程中,听觉阈值由经过培训的工作人员从声压升高的信号曲线系列中进行视觉评估。这需要时间,而且容易受到读者以及图形显示质量和规模的偏差。为了降低工作量,改进质量和可复制性,我们开发并比较了两种从平均听觉反应(ABR)反应(ABR 原始数据) 自动辨识临界值的方法:一种由两个经过人造标签培训的混合神经网络和一种自我监督的方法。 这种方法利用信号频谱,将随机的精密的基因级水平估计结果,以及一个用于快速测听觉检查的快速检查的临界水平,我们测测定的临界的临界标准。