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1.
Mol Syst Biol ; 16(10): e9474, 2020 10.
Article in English | MEDLINE | ID: mdl-33022142

ABSTRACT

The advent of single-cell methods is paving the way for an in-depth understanding of the cell cycle with unprecedented detail. Due to its ramifications in nearly all biological processes, the evaluation of cell cycle progression is critical for an exhaustive cellular characterization. Here, we present DeepCycle, a deep learning method for estimating a cell cycle trajectory from unsegmented single-cell microscopy images, relying exclusively on the brightfield and nuclei-specific fluorescent signals. DeepCycle was evaluated on 2.6 million single-cell microscopy images of MDCKII cells with the fluorescent FUCCI2 system. DeepCycle provided a latent representation of cell images revealing a continuous and closed trajectory of the cell cycle. Further, we validated the DeepCycle trajectories by showing its nearly perfect correlation with real time measured from live-cell imaging of cells undergoing an entire cell cycle. This is the first model able to resolve the closed cell cycle trajectory, including cell division, solely based on unsegmented microscopy data from adherent cell cultures.


Subject(s)
Cell Cycle , Image Processing, Computer-Assisted/methods , Single-Cell Analysis/methods , Time-Lapse Imaging/methods , Animals , Cell Line , Dogs , Microscopy, Fluorescence , Neural Networks, Computer
2.
Bioinformatics ; 36(10): 3215-3224, 2020 05 01.
Article in English | MEDLINE | ID: mdl-32049317

ABSTRACT

MOTIVATION: Imaging mass spectrometry (imaging MS) is a prominent technique for capturing distributions of molecules in tissue sections. Various computational methods for imaging MS rely on quantifying spatial correlations between ion images, referred to as co-localization. However, no comprehensive evaluation of co-localization measures has ever been performed; this leads to arbitrary choices and hinders method development. RESULTS: We present ColocML, a machine learning approach addressing this gap. With the help of 42 imaging MS experts from nine laboratories, we created a gold standard of 2210 pairs of ion images ranked by their co-localization. We evaluated existing co-localization measures and developed novel measures using term frequency-inverse document frequency and deep neural networks. The semi-supervised deep learning Pi model and the cosine score applied after median thresholding performed the best (Spearman 0.797 and 0.794 with expert rankings, respectively). We illustrate these measures by inferring co-localization properties of 10 273 molecules from 3685 public METASPACE datasets. AVAILABILITY AND IMPLEMENTATION: https://github.com/metaspace2020/coloc. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.


Subject(s)
Machine Learning , Neural Networks, Computer , Mass Spectrometry , Software , Supervised Machine Learning
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