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体内线虫身体分割:基于机器学习对固定在体内芯片中的秀丽隐杆线虫进行分析,用于自动化发育毒性测试。

vivoBodySeg: Machine learning-based analysis of C. elegans immobilized in vivoChip for automated developmental toxicity testing.

作者信息

DuPlissis Andrew, Medewar Abhishri, Hegarty Evan, Laing Adam, Shen Amber, Gomez Sebastian, Mondal Sudip, Ben-Yakar Adela

机构信息

vivoVerse, LLC.

出版信息

Res Sq. 2024 Sep 4:rs.3.rs-4796642. doi: 10.21203/rs.3.rs-4796642/v1.

Abstract

Developmental toxicity (DevTox) tests evaluate the adverse effects of chemical exposures on an organism's development. While large animal tests are currently heavily relied on, the development of new approach methodologies (NAMs) is encouraging industries and regulatory agencies to evaluate these novel assays. Several practical advantages have made useful model for rapid toxicity testing and studying developmental biology. Although the potential to study DevTox is promising, current low-resolution and labor-intensive methodologies prohibit the use of for sub-lethal DevTox studies at high throughputs. With the recent availability of a large-scale microfluidic device, vivoChip, we can now rapidly collect 3D high-resolution images of ~ 1,000 from 24 different populations. In this paper, we demonstrate DevTox studies using a 2.5D U-Net architecture (vivoBodySeg) that can precisely segment in images obtained from vivoChip devices, achieving an average Dice score of 97.80. The fully automated platform can analyze 36 GB data from each device to phenotype multiple body parameters within 35 min on a desktop PC at speeds ~ 140x faster than the manual analysis. Highly reproducible DevTox parameters (4-8% CV) and additional autofluorescence-based phenotypes allow us to assess the toxicity of chemicals with high statistical power.

摘要

发育毒性(DevTox)测试评估化学物质暴露对生物体发育的不利影响。虽然目前严重依赖大型动物试验,但新方法学(NAMs)的发展正促使行业和监管机构评估这些新的检测方法。一些实际优势使其成为快速毒性测试和研究发育生物学的有用模型。尽管研究发育毒性的潜力很有前景,但目前低分辨率和劳动密集型的方法阻碍了其在高通量亚致死发育毒性研究中的应用。随着最近大规模微流控设备vivoChip的出现,我们现在可以从24个不同群体中快速收集约1000个样本的3D高分辨率图像。在本文中,我们展示了使用2.5D U-Net架构(vivoBodySeg)进行的发育毒性研究,该架构可以精确分割从vivoChip设备获得的图像中的样本,平均骰子系数达到97.80。这个全自动平台可以在台式电脑上35分钟内分析来自每个设备的36GB数据,以对多个身体参数进行表型分析,速度比手动分析快约140倍。高度可重复的发育毒性参数(变异系数为4-8%)和基于自发荧光的其他表型使我们能够以高统计效力评估化学物质的毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/a10f6e3a551b/nihpp-rs4796642v1-f0001.jpg

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