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A machine learning approach for single cell interphase cell cycle staging.

ABSTRACT: The cell nucleus is a tightly regulated organelle and its architectural structure is dynamically orchestrated to maintain normal cell function. Indeed, fluctuations in nuclear size and shape are known to occur during the cell cycle and alterations in nuclear morphology are also hallmarks of many diseases including cancer. Regrettably, automated reliable tools for cell cycle staging at single cell level using in situ images are still limited. It is therefore urgent to establish accurate strategies combining bioimaging with high-content image analysis for a bona fide classification. In this study we developed a supervised machine learning method for interphase cell cycle staging of individual adherent cells using in situ fluorescence images of nuclei stained with DAPI. A Support Vector Machine (SVM) classifier operated over normalized nuclear features using more than 3500 DAPI stained nuclei. Molecular ground truth labels were obtained by automatic image processing using fluorescent ubiquitination-based cell cycle indicator (Fucci) technology. An average F1-Score of 87.7% was achieved with this framework. Furthermore, the method was validated on distinct cell types reaching recall values higher than 89%. Our method is a robust approach to identify cells in G₁ or S/G₂ at the individual level, with implications in research and clinical applications.

SUBMITTER: Narotamo H

PROVIDER: S-EPMC8481278 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundBone age assessment (BAA) is used in numerous pediatric clinical settings as well as in legal settings when entities need an estimate of chronological age (CA) when valid documents are lacking. The latter case presents itself as critical as the law is harsher for adults and granted rights along with imputability changes drastically if the individual is a minor. Traditional BAA methods have drawbacks such as exposure of minors to radiation, they do not consider factors that might affect the bone age, and they mostly focus on a single region. Given the critical scenarios in which BAA can affect the lives of young individuals, it is important to focus on the drawbacks of the traditional methods and investigate the potential of estimating CA through BAA.ObjectiveThis study aims to investigate CA estimation through BAA in young individuals aged 14-21 years with machine learning methods, addressing the drawbacks of research using magnetic resonance imaging (MRI), assessment of multiple regions of interest, and other factors that may affect the bone age.MethodsMRI examinations of the radius, distal tibia, proximal tibia, distal femur, and calcaneus were performed on 465 men and 473 women (aged 14-21 years). Measures of weight and height were taken from the subjects, and a questionnaire was given for additional information (self-assessed Tanner Scale, physical activity level, parents' origin, and type of residence during upbringing). Two pediatric radiologists independently assessed the MRI images to evaluate their stage of bone development (blinded to age, gender, and each other). All the gathered information was used in training machine learning models for CA estimation and minor versus adult classification (threshold of 18 years). Different machine learning methods were investigated.ResultsThe minor versus adult classification produced accuracies of 0.90 and 0.84 for male and female subjects, respectively, with high recalls for the classification of minors. The CA estimation for the 8 age groups (aged 14-21 years) achieved mean absolute errors of 0.95 years and 1.24 years for male and female subjects, respectively. However, for the latter, a lower error occurred only for the ages of 14 and 15 years.ConclusionsThis study investigates CA estimation through BAA using machine learning methods in 2 ways: minor versus adult classification and CA estimation in 8 age groups (aged 14-21 years), while addressing the drawbacks in the research on BAA. The first achieved good results; however, for the second case, the BAA was not precise enough for the classification.

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A machine learning approach for single cell interphase cell cycle staging.

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