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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.

DOI:10.21203/rs.3.rs-4796642/v1
PMID:39281859
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11398583/
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/f129/11398583/5c752988ddba/nihpp-rs4796642v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/a10f6e3a551b/nihpp-rs4796642v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/7fc9228887b5/nihpp-rs4796642v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/722ab3332f1e/nihpp-rs4796642v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/ed3629d2bbc1/nihpp-rs4796642v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/2423c865dc4d/nihpp-rs4796642v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/5c752988ddba/nihpp-rs4796642v1-f0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/a10f6e3a551b/nihpp-rs4796642v1-f0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/7fc9228887b5/nihpp-rs4796642v1-f0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/722ab3332f1e/nihpp-rs4796642v1-f0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/ed3629d2bbc1/nihpp-rs4796642v1-f0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/2423c865dc4d/nihpp-rs4796642v1-f0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f129/11398583/5c752988ddba/nihpp-rs4796642v1-f0006.jpg

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本文引用的文献

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WormSwin: Instance segmentation of C. elegans using vision transformer.基于视觉Transformer 的秀丽隐杆线虫实例分割
Sci Rep. 2023 Jul 7;13(1):11021. doi: 10.1038/s41598-023-38213-7.
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Genetic factors in methylmercury-induced neurotoxicity: What have we learned from models?甲基汞诱导神经毒性中的遗传因素:我们从模型中学到了什么?
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Automatic segmentation of skeletons in worm aggregations using improved U-Net in low-resolution image sequences.
在低分辨率图像序列中使用改进的U-Net自动分割蠕虫聚集体中的骨骼
Heliyon. 2023 Mar 22;9(4):e14715. doi: 10.1016/j.heliyon.2023.e14715. eCollection 2023 Apr.
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Comparing 3D, 2.5D, and 2D Approaches to Brain Image Auto-Segmentation.比较3D、2.5D和2D方法在脑图像自动分割中的应用
Bioengineering (Basel). 2023 Feb 1;10(2):181. doi: 10.3390/bioengineering10020181.
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Changes in body shape implicate cuticle stretch in C. elegans growth control.身体形状的变化表明线虫生长控制中角质层的拉伸。
Cells Dev. 2022 Jun;170:203780. doi: 10.1016/j.cdev.2022.203780. Epub 2022 Apr 19.
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Deep learning for robust and flexible tracking in behavioral studies for C. elegans.用于秀丽隐杆线虫行为研究中鲁棒且灵活跟踪的深度学习。
PLoS Comput Biol. 2022 Apr 8;18(4):e1009942. doi: 10.1371/journal.pcbi.1009942. eCollection 2022 Apr.
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Developmental Exposure to Low Concentrations of Methylmercury Causes Increase in Anxiety-Related Behaviour and Locomotor Impairments in Zebrafish.发育暴露于低浓度甲基汞会导致斑马鱼出现焦虑相关行为和运动障碍。
Int J Mol Sci. 2021 Oct 11;22(20):10961. doi: 10.3390/ijms222010961.
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Ecotoxicity Risk of Low-Dose Methylmercury Exposure to : Multigenerational Toxicity and Population Discrepancy.低剂量甲基汞暴露对的生态毒性风险:多代毒性和种群差异。
Chem Res Toxicol. 2021 Apr 19;34(4):1114-1123. doi: 10.1021/acs.chemrestox.0c00518. Epub 2021 Mar 19.
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