CellCognition: Time-resolved Phenotype Annotation in High-throughput Live Cell Imaging

Overview

Journal Nat Methods

Specialties Biomedical Engineering
Pathology

Date 2010 Aug 10

PMID 20693996

Citations 169

Authors

Michael Held

Michael H A Schmitz

Bernd Fischer

Thomas Walter

Beate Neumann

Michael H Olma

Matthias Peter

Jan Ellenberg

Daniel W Gerlich

Affiliations

Soon will be listed here.

Abstract

Fluorescence time-lapse imaging has become a powerful tool to investigate complex dynamic processes such as cell division or intracellular trafficking. Automated microscopes generate time-resolved imaging data at high throughput, yet tools for quantification of large-scale movie data are largely missing. Here we present CellCognition, a computational framework to annotate complex cellular dynamics. We developed a machine-learning method that combines state-of-the-art classification with hidden Markov modeling for annotation of the progression through morphologically distinct biological states. Incorporation of time information into the annotation scheme was essential to suppress classification noise at state transitions and confusion between different functional states with similar morphology. We demonstrate generic applicability in different assays and perturbation conditions, including a candidate-based RNA interference screen for regulators of mitotic exit in human cells. CellCognition is published as open source software, enabling live-cell imaging-based screening with assays that directly score cellular dynamics.

Citing Articles

The DEAD-box helicase eIF4A1/2 acts as RNA chaperone during mitotic exit enabling chromatin decondensation.

Juhlen R, Wiesmann S, Scheufen A, Stausberg T, Braun I, Strobel C Nat Commun. 2025; 16(1):2434.

PMID: 40069174 PMC: 11897408. DOI: 10.1038/s41467-025-57592-1.

Quantitative Live-Cell Imaging to Study Chromatin Segregation and Nuclear Reformation.

Scheufen A, Moreno-Andres D Methods Mol Biol. 2024; 2874:47-60.

PMID: 39614046 DOI: 10.1007/978-1-0716-4236-8_5.

Exploring heterogeneous cell population dynamics in different microenvironments by novel analytical strategy based on images.

Huang Y, Zhou Z, Liu T, Tang S, Xin X NPJ Syst Biol Appl. 2024; 10(1):129.

PMID: 39505883 PMC: 11542073. DOI: 10.1038/s41540-024-00459-w.

Predicting cell cycle stage from 3D single-cell nuclear-stained images.

Li G, Nichols E, Browning V, Longhi N, Camplisson C, Beliveau B bioRxiv. 2024; .

PMID: 39257739 PMC: 11383680. DOI: 10.1101/2024.08.30.610553.

Spatiotemporal multi-omics: exploring molecular landscapes in aging and regenerative medicine.

Chu L, Wang W, Gu X, Wu P, Gao C, Zhang Q Mil Med Res. 2024; 11(1):31.

PMID: 38797843 PMC: 11129507. DOI: 10.1186/s40779-024-00537-4.

References

Zhou X, Li F, Yan J, Wong S . A novel cell segmentation method and cell phase identification using Markov model. IEEE Trans Inf Technol Biomed. 2009; 13(2):152-7. PMC: 2846548. DOI: 10.1109/TITB.2008.2007098. View

Conrad C, Gerlich D . Automated microscopy for high-content RNAi screening. J Cell Biol. 2010; 188(4):453-61. PMC: 2828931. DOI: 10.1083/jcb.200910105. View

Chen X, Zhou X, Wong S . Automated segmentation, classification, and tracking of cancer cell nuclei in time-lapse microscopy. IEEE Trans Biomed Eng. 2006; 53(4):762-6. DOI: 10.1109/TBME.2006.870201. View

Bollen M, Gerlich D, Lesage B . Mitotic phosphatases: from entry guards to exit guides. Trends Cell Biol. 2009; 19(10):531-41. DOI: 10.1016/j.tcb.2009.06.005. View

Wang M, Zhou X, King R, Wong S . Context based mixture model for cell phase identification in automated fluorescence microscopy. BMC Bioinformatics. 2007; 8:32. PMC: 1800869. DOI: 10.1186/1471-2105-8-32. View

Erfle H, Neumann B, Liebel U, Rogers P, Held M, Walter T . Reverse transfection on cell arrays for high content screening microscopy. Nat Protoc. 2007; 2(2):392-9. DOI: 10.1038/nprot.2006.483. View

Schaub B, Berger B, Berger E, Rohrer J . Transition of galactosyltransferase 1 from trans-Golgi cisterna to the trans-Golgi network is signal mediated. Mol Biol Cell. 2006; 17(12):5153-62. PMC: 1679680. DOI: 10.1091/mbc.e06-08-0665. View

Loo L, Wu L, Altschuler S . Image-based multivariate profiling of drug responses from single cells. Nat Methods. 2007; 4(5):445-53. DOI: 10.1038/nmeth1032. View

Goshima G, Wollman R, Goodwin S, Zhang N, Scholey J, Vale R . Genes required for mitotic spindle assembly in Drosophila S2 cells. Science. 2007; 316(5823):417-21. PMC: 2837481. DOI: 10.1126/science.1141314. View

10.

Meraldi P, Draviam V, Sorger P . Timing and checkpoints in the regulation of mitotic progression. Dev Cell. 2004; 7(1):45-60. DOI: 10.1016/j.devcel.2004.06.006. View

11.

Gerlich D, Ellenberg J . 4D imaging to assay complex dynamics in live specimens. Nat Cell Biol. 2003; Suppl:S14-9. View

12.

Dultz E, Zanin E, Wurzenberger C, Braun M, Rabut G, Sironi L . Systematic kinetic analysis of mitotic dis- and reassembly of the nuclear pore in living cells. J Cell Biol. 2008; 180(5):857-65. PMC: 2265396. DOI: 10.1083/jcb.200707026. View

13.

Wang M, Zhou X, Li F, Huckins J, King R, Wong S . Novel cell segmentation and online SVM for cell cycle phase identification in automated microscopy. Bioinformatics. 2007; 24(1):94-101. DOI: 10.1093/bioinformatics/btm530. View

14.

Wahlby C, Sintorn I, Erlandsson F, Borgefors G, Bengtsson E . Combining intensity, edge and shape information for 2D and 3D segmentation of cell nuclei in tissue sections. J Microsc. 2004; 215(Pt 1):67-76. DOI: 10.1111/j.0022-2720.2004.01338.x. View

15.

Schmitz M, Gerlich D . Automated live microscopy to study mitotic gene function in fluorescent reporter cell lines. Methods Mol Biol. 2009; 545:113-34. DOI: 10.1007/978-1-60327-993-2_7. View

16.

Steigemann P, Wurzenberger C, Schmitz M, Held M, Guizetti J, Maar S . Aurora B-mediated abscission checkpoint protects against tetraploidization. Cell. 2009; 136(3):473-84. DOI: 10.1016/j.cell.2008.12.020. View

17.

Neumann B, Walter T, Heriche J, Bulkescher J, Erfle H, Conrad C . Phenotypic profiling of the human genome by time-lapse microscopy reveals cell division genes. Nature. 2010; 464(7289):721-7. PMC: 3108885. DOI: 10.1038/nature08869. View

18.

Sonnichsen B, Koski L, Walsh A, Marschall P, Neumann B, Brehm M . Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature. 2005; 434(7032):462-9. DOI: 10.1038/nature03353. View

19.

Collinet C, Stoter M, Bradshaw C, Samusik N, Rink J, Kenski D . Systems survey of endocytosis by multiparametric image analysis. Nature. 2010; 464(7286):243-9. DOI: 10.1038/nature08779. View

20.

Glory E, Murphy R . Automated subcellular location determination and high-throughput microscopy. Dev Cell. 2007; 12(1):7-16. DOI: 10.1016/j.devcel.2006.12.007. View