Analysis of Cell Lineage Trees by Exact Bayesian Inference Identifies Negative Autoregulation of Nanog in Mouse Embryonic Stem Cells

Cell Systems
Justin FeigelmanManfred Claassen

Abstract

Many cellular effectors of pluripotency are dynamically regulated. In principle, regulatory mechanisms can be inferred from single-cell observations of effector activity across time. However, rigorous inference techniques suitable for noisy, incomplete, and heterogeneous data are lacking. Here, we introduce stochastic inference on lineage trees (STILT), an algorithm capable of identifying stochastic models that accurately describe the quantitative behavior of cell fate markers observed using time-lapse microscopy data collected from proliferating cell populations. STILT performs exact Bayesian parameter inference and stochastic model selection using a particle-filter-based algorithm. We use STILT to investigate the autoregulation of Nanog, a heterogeneously expressed core pluripotency factor, in mouse embryonic stem cells. STILT rejects the possibility of positive Nanog autoregulation with high confidence; instead, model predictions indicate weak negative feedback. We use STILT for rational experimental design and validate model predictions using novel experimental data. STILT is available for download as an open source framework from http://www.imsb.ethz.ch/research/claassen/Software/stilt---stochastic-inference-on-lineage-tre...Continue Reading

References

Dec 17, 2017·Journal of Mathematical Biology·Frits VeermanNikola Popović
Feb 13, 2019·PLoS Computational Biology·Damien G HicksSarah M Russell
Nov 2, 2018·Journal of the Royal Society, Interface·Steffen Waldherr
Jan 31, 2018·Molecular Systems Biology·Ayako Yachie-KinoshitaPeter W Zandstra
Apr 28, 2017·BMC Systems Biology·Irena KuzmanovskaMustafa Khammash
Mar 16, 2019·Nature Communications·Nicholas E PhillipsDavid M Suter
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Feb 17, 2018·PLoS Computational Biology·Yen Ting LinDavit A Potoyan
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Citations

Oct 20, 2006·PLoS Biology·Arjun RajSanjay Tyagi
Dec 22, 2007·Nature·Ian ChambersAustin Smith
Apr 14, 2009·Nature·Sabrina L SpencerPeter K Sorger
May 20, 2011·Nature·Björn SchwanhäusserMatthias Selbach
Feb 15, 2013·Nature·Björn SchwanhäusserMatthias Selbach
May 30, 2013·Methods in Molecular Biology·Andrew Golightly, Colin S Gillespie
Aug 15, 2013·Journal of Cell Science·Daniel L Coutu, Timm Schroeder
Jul 13, 2016·Nature Biotechnology·Oliver HilsenbeckTimm Schroeder

Related Concepts

Computer Software
Biological Markers
Fluctuation
Observational Study
Bone Structure of Middle Phalanx
Research
Protein Degradation, Regulatory
Transfection
Cell Fate
EXOSC10 gene

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