Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells
Abstract Label-free image analysis has several advantages with respect to the development of drug screening platforms. However, the evaluation of drug-responsive cells based exclusively on morphological information is challenging, especially in cases of morphologically heterogeneous cells or a small...
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| Format: | Article |
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Nature Portfolio
2022-06-01
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| Series: | Scientific Reports |
| Online Access: | https://doi.org/10.1038/s41598-022-12250-0 |
| _version_ | 1811343474560073728 |
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| author | Yuta Imai Madoka Iida Kei Kanie Masahisa Katsuno Ryuji Kato |
| author_facet | Yuta Imai Madoka Iida Kei Kanie Masahisa Katsuno Ryuji Kato |
| author_sort | Yuta Imai |
| collection | DOAJ |
| description | Abstract Label-free image analysis has several advantages with respect to the development of drug screening platforms. However, the evaluation of drug-responsive cells based exclusively on morphological information is challenging, especially in cases of morphologically heterogeneous cells or a small subset of drug-responsive cells. We developed a novel label-free cell sub-population analysis method called “in silico FOCUS (in silico analysis of featured-objects concentrated by anomaly discrimination from unit space)” to enable robust phenotypic screening of morphologically heterogeneous spinal and bulbar muscular atrophy (SBMA) model cells. This method with the anomaly discrimination concept can sensitively evaluate drug-responsive cells as morphologically anomalous cells through in silico cytometric analysis. As this algorithm requires only morphological information of control cells for training, no labeling or drug administration experiments are needed. The responses of SBMA model cells to dihydrotestosterone revealed that in silico FOCUS can identify the characteristics of a small sub-population with drug-responsive phenotypes to facilitate robust drug response profiling. The phenotype classification model confirmed with high accuracy the SBMA-rescuing effect of pioglitazone using morphological information alone. In silico FOCUS enables the evaluation of delicate quality transitions in cells that are difficult to profile experimentally, including primary cells or cells with no known markers. |
| first_indexed | 2024-04-13T19:29:47Z |
| format | Article |
| id | doaj.art-2e0fd524b5e244ecb274dde891e0981f |
| institution | Directory Open Access Journal |
| issn | 2045-2322 |
| language | English |
| last_indexed | 2024-04-13T19:29:47Z |
| publishDate | 2022-06-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj.art-2e0fd524b5e244ecb274dde891e0981f2022-12-22T02:33:13ZengNature PortfolioScientific Reports2045-23222022-06-0112111310.1038/s41598-022-12250-0Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cellsYuta Imai0Madoka Iida1Kei Kanie2Masahisa Katsuno3Ryuji Kato4Department of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research SystemDepartment of Neurology, Nagoya University Graduate School of Medicine, Tokai National Higher Education and Research SystemDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research SystemDepartment of Neurology, Nagoya University Graduate School of Medicine, Tokai National Higher Education and Research SystemDepartment of Basic Medicinal Sciences, Graduate School of Pharmaceutical Sciences, Nagoya University, Tokai National Higher Education and Research SystemAbstract Label-free image analysis has several advantages with respect to the development of drug screening platforms. However, the evaluation of drug-responsive cells based exclusively on morphological information is challenging, especially in cases of morphologically heterogeneous cells or a small subset of drug-responsive cells. We developed a novel label-free cell sub-population analysis method called “in silico FOCUS (in silico analysis of featured-objects concentrated by anomaly discrimination from unit space)” to enable robust phenotypic screening of morphologically heterogeneous spinal and bulbar muscular atrophy (SBMA) model cells. This method with the anomaly discrimination concept can sensitively evaluate drug-responsive cells as morphologically anomalous cells through in silico cytometric analysis. As this algorithm requires only morphological information of control cells for training, no labeling or drug administration experiments are needed. The responses of SBMA model cells to dihydrotestosterone revealed that in silico FOCUS can identify the characteristics of a small sub-population with drug-responsive phenotypes to facilitate robust drug response profiling. The phenotype classification model confirmed with high accuracy the SBMA-rescuing effect of pioglitazone using morphological information alone. In silico FOCUS enables the evaluation of delicate quality transitions in cells that are difficult to profile experimentally, including primary cells or cells with no known markers.https://doi.org/10.1038/s41598-022-12250-0 |
| spellingShingle | Yuta Imai Madoka Iida Kei Kanie Masahisa Katsuno Ryuji Kato Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells Scientific Reports |
| title | Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells |
| title_full | Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells |
| title_fullStr | Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells |
| title_full_unstemmed | Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells |
| title_short | Label-free morphological sub-population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells |
| title_sort | label free morphological sub population cytometry for sensitive phenotypic screening of heterogenous neural disease model cells |
| url | https://doi.org/10.1038/s41598-022-12250-0 |
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