Abstract：
:Current developmental neurotoxicity (DNT) testing in animals faces major limitations, such as high cost and time demands as well as uncertainties in their methodology, evaluation and regulation. Therefore, the use of human-based 3D in vitro systems in combination with high-content image analysis (HCA) might contribute to DNT testing with lower costs, increased throughput and enhanced predictivity for human hazard identification. Human neural progenitor cells (hNPCs) grown as 3D neurospheres mimic basic processes of brain development including hNPC migration and differentiation and are therefore useful for DNT hazard identification. HCA of migrated neurospheres creates new challenges for automated evaluations because it encompasses variable cell densities, inconsistent z-layers and heterogeneous cell populations. We tackle those challenges with our Omnisphero software, which assesses multiple endpoints of the 'Neurosphere Assay.' For neuronal identification, Omnisphero reaches a true positive rate (TPR) of 83.8 % and a false discovery rate (FDR) of 11.4 %, thus being comparable to the interindividual difference among two researchers (TPR = 94.3, FDR = 11.0 %) and largely improving the results obtained by an existing HCA approach, whose TPR does not exceed 50 % at a FDR above 50 %. The high FDR of existing methods results in incorrect measurements of neuronal morphological features accompanied by an overestimation of compound effects. Omnisphero additionally includes novel algorithms to assess 'neurosphere-specific' endpoints like radial migration and neuronal density distribution within the migration area. Furthermore, a user-assisted parameter optimization procedure makes Omnisphero accessible to non-expert end users.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Schmuck MR,Temme T,Dach K,de Boer D,Barenys M,Bendt F,Mosig A,Fritsche Edoi
10.1007/s00204-016-1852-2subject
Has Abstractpub_date
2017-04-01 00:00:00pages
2017-2028issue
4eissn
0340-5761issn
1432-0738pii
10.1007/s00204-016-1852-2journal_volume
91pub_type
杂志文章abstract：:The trichothecene mycotoxin deoxynivalenol (DON) is produced in wheat, barley and corn following infestation by the fungus Fusarium in the field and during storage. Colloquially known as "vomitoxin" because of its emetic effects in pigs, DON has been associated with human gastroenteritis. Since DON is commonly detecte...
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050495
更新日期：1998-03-01 00:00:00
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pub_type： 杂志文章
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pub_type： 杂志文章
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journal_title：Archives of toxicology
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journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：1997-01-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：1980-07-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
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更新日期：1997-01-01 00:00:00
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journal_title：Archives of toxicology
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更新日期：1983-02-01 00:00:00
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journal_title：Archives of toxicology
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