- ArticleNegative frequency‐dependent interactions can underlie phenotypic heterogeneity in a clonal microbial population
- 1Department of Biology, Massachusetts Institute of Technology, Cambridge, MA, USA
- 2Graduate Program in Biophysics, Harvard University, Cambridge, MA, USA
- 3Department of Physics, Massachusetts Institute of Technology, Cambridge, MA, USA
- ↵*Corresponding author. Tel: +1 6172534829; E‐mail: gore{at}mit.edu
Analyses of the yeast GAL network show that phenotypic heterogeneity can result from negative frequency‐dependent interactions favoring rare phenotypes over common ones and indicate that a stochastic “mixed strategy” of GAL activation is evolutionarily favorable.
Synopsis
Analyses of the yeast GAL network show that phenotypic heterogeneity can result from negative frequency‐dependent interactions favoring rare phenotypes over common ones and indicate that a stochastic “mixed strategy” of GAL activation is evolutionarily favorable.
In an environment of finite mixed glucose and galactose, yeast strains that are “always ON” or “always OFF” with respect to the GAL network can each invade the other when rare, and there exists an evolutionarily stable mix of the two.
A yeast strain that stochastically activates or deactivates the GAL network in this environment is evolutionarily favored against both pure strategist strains.
A stochastic GAL‐ON/OFF “mixed strategy” can consistently evolve de novo from a pure strategist strain by exposure to mixed glucose and galactose environments over many generations.
Therefore, in addition to the more common explanation of environmental bet hedging, frequency‐dependent selection may also drive phenotypic heterogeneity in clonal microbial populations.
Mol Syst Biol. (2016) 12: 877
- Received April 25, 2016.
- Revision received June 28, 2016.
- Accepted July 4, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- News & ViewsFrequency‐dependent selection: a diversifying force in microbial populations
The benefits of “bet‐hedging” strategies have been assumed to be the main cause of phenotypic diversity in biological populations. However, in their recent work, Healey et al (2016) provide experimental support for negative frequency‐dependent selection (NFDS) as an alternative driving force of diversity. NFDS favors rare phenotypes over common ones, resulting in an evolutionarily stable mixture of phenotypes that is not necessarily optimal for population growth.
See also: D Healey et al (August 2016)
The benefits of “bet‐hedging” strategies have been assumed to be the main cause of phenotypic population diversity. However, Healey et al (2016) provide experimental support for negative frequency‐dependent selection as an alternative driving force of diversity.
Mol Syst Biol. (2016) 12: 880
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- ReportParallel reverse genetic screening in mutant human cells using transcriptomics
- Bianca V Gapp1,†,
- Tomasz Konopka1,†,
- Thomas Penz2,
- Vineet Dalal1,
- Tilmann Bürckstümmer3,
- Christoph Bock2,4,5 and
- Sebastian MB Nijman*,1,2,6
- 1Nuffield Department of Clinical Medicine, Ludwig Cancer Research Ltd. University of Oxford, Oxford, UK
- 2CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, Vienna, Austria
- 3Horizon Genomics, Vienna, Austria
- 4Department of Laboratory Medicine, Medical University of Vienna, Vienna, Austria
- 5Max Planck Institute for Informatics, Saarbrücken, Germany
- 6Nuffield Department of Clinical Medicine, Target Discovery Institute University of Oxford, Oxford, UK
- ↵*Corresponding author. Tel: +44 1865 612885; E‐mail: Sebastian.nijman{at}ludwig.ox.ac.uk
↵† These authors contributed equally to this work
Genome editing and transcriptomic profiling enable reverse genetic exploration of gene function in human cells. Ten parallel screens of tyrosine kinase knock‐out cells reveal quantitative and qualitative changes in signaling upon genetic perturbations.
Synopsis
Genome editing and transcriptomic profiling enable reverse genetic exploration of gene function in human cells. Ten parallel screens of tyrosine kinase knock‐out cells reveal quantitative and qualitative changes in signaling upon genetic perturbations.
A collection of isogenic kinase knock‐out cell lines are generated by genome editing using CRISPR/Cas9.
Shallow and highly multiplexed RNA sequencing provides a robust and scalable assay for phenotyping hundreds of samples that is suitable for screening.
The responses of mutant cell lines to diverse external perturbations reveal varying degrees of signaling changes, linking genes to pathways.
Mol Syst Biol. (2016) 12: 879
- Received February 16, 2016.
- Revision received July 6, 2016.
- Accepted July 7, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- ReviewDeep learning for computational biology
- 1European Molecular Biology Laboratory, European Bioinformatics Institute, Wellcome Trust Genome Campus, Hinxton Cambridge, UK
- 2Department of Computer Science, University of Tartu, Tartu, Estonia
- 3Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton Cambridge, UK
- ↵*
Corresponding author. Tel: +44 1223 834 244; E‐mail: leopold.parts{at}sanger.ac.uk
Corresponding author. Tel: +44 1223 494 101; E‐mail: oliver.stegle{at}ebi.ac.uk
↵† These authors contributed equally to this work
Deep learning, a class of modern machine learning methods, has become a go‐to approach for analysing large‐scale high‐dimensional data. This review discusses its applications in biology, focusing on regulatory genomics and cellular imaging, and gives guidelines for practitioners.
Mol Syst Biol. (2016) 12: 878
- Received April 11, 2016.
- Revision received June 2, 2016.
- Accepted June 6, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- ArticleCo‐recruitment analysis of the CBL and CBLB signalosomes in primary T cells identifies CD5 as a key regulator of TCR‐induced ubiquitylation
- Guillaume Voisinne1,†,
- Antonio García‐Blesa1,†,
- Karima Chaoui2,
- Frédéric Fiore3,
- Elise Bergot1,
- Laura Girard1,3,
- Marie Malissen1,3,
- Odile Burlet‐Schiltz2,
- Anne Gonzalez de Peredo2,
- Bernard Malissen*,1,3 and
- Romain Roncagalli*,1
- 1Centre d'Immunologie de Marseille‐Luminy, Aix Marseille Université, Inserm, CNRS, Marseille, France
- 2Institut de Pharmacologie et de Biologie Structurale, Département Biologie Structural Biophysique, Protéomique Génopole Toulouse Midi Pyrénées, CNRS UMR 5089, Toulouse Cedex, France
- 3Centre d'Immunophénomique, Aix Marseille Université UM2, Inserm US012, CNRS UMS3367, Marseille, France
- ↵*
Corresponding author. Tel: +33 491269478; Fax: +33 491269430; E‐mail: bernardm{at}ciml.univ-mrs.fr
Corresponding author. Tel: +33 491269478; Fax: +33 491269430; E‐mail: roncagalli{at}ciml.univ-mrs.fr
↵† These authors contributed equally to this work
The composition and dynamics of the signalosomes operated by the E3 ubiquitin–protein ligases CBL and CBLB were determined in primary T cells after TCR stimulation. Analysis of correlations in protein association as a function of time reveals the importance of the CD5 transmembrane receptor in the regulation of ubiquitylation.
Synopsis
The composition and dynamics of the signalosomes operated by the E3 ubiquitin–protein ligases CBL and CBLB were determined in primary T cells after TCR stimulation. Analysis of correlations in protein association as a function of time reveals the importance of the CD5 transmembrane receptor in the regulation of ubiquitylation.
The signalosomes of the E3‐ubiquitin ligases CBL and CBLB exhibit both redundant and distinct features in mature CD4+ T cells.
Analysis of correlations in protein association with CBL and CBLB accurately predicts interactions between recruited proteins.
CD5 is identified as a key regulator of CBL‐ and CBLB‐mediated ubiquitylation following TCR engagement.
Mol Syst Biol. (2016) 12: 876
- Received January 26, 2016.
- Revision received June 14, 2016.
- Accepted June 23, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- ArticlePervasive isoform‐specific translational regulation via alternative transcription start sites in mammals
- 1Laboratory for Functional Genomics and Systems Biology, Berlin Institute for Medical Systems Biology, Max‐Delbrück‐Centrum für Molekulare Medizin, Berlin, Germany
- 2Department of Biology, South University of Science and Technology of China, Shenzhen, Guangdong, China
- ↵*Corresponding author. Tel: +86 75588018449; E‐mails: wei.chen{at}mdc-berlin.de; chenw{at}sustc.edu.cn
↵† These authors contributed equally to this work
Polysome profiling combined with 5ʹ‐end sequencing in mouse fibroblasts shows pervasive isoform‐specific translational regulation via alternative transcription start sites (TSSs) and reveals 5′UTR sequence features linked to translational regulation.
Synopsis
Polysome profiling combined with 5ʹ‐end sequencing in mouse fibroblasts shows pervasive isoform‐specific translational regulation via alternative transcription start sites (TSSs) and reveals 5′UTR sequence features linked to translational regulation.
Isoform‐specific translational regulation is achieved through alternative TSS usage.
Isoforms with longer 5ʹUTRs tend to have lower translational efficiency (TE).
Systematic analyses of isoform‐specific translation offer new insights into the regulation by known sequence features and identifies novel regulatory sequence motifs.
Quantitative models integrating all identified sequence features explain over half of the variance in the observed TE divergence between isoforms.
Mol Syst Biol. (2016) 12: 875
- Received March 10, 2016.
- Revision received June 17, 2016.
- Accepted June 21, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
- ArticleStrand‐specific, high‐resolution mapping of modified RNA polymerase II
- Laura Milligan1,
- Vân A Huynh‐Thu2,3,
- Clémentine Delan‐Forino1,
- Alex Tuck1,4,5,
- Elisabeth Petfalski1,
- Rodrigo Lombraña6,
- Guido Sanguinetti*,2,
- Grzegorz Kudla*,6 and
- David Tollervey*,1
- 1Wellcome Trust Centre for Cell Biology, University of Edinburgh, Edinburgh, UK
- 2School of Informatics, University of Edinburgh, Edinburgh, UK
- 3Department of Electrical Engineering and Computer Science, University of Liège, Liège, Belgium
- 4Friedrich Miescher Institute for Biomedical Research, Basel, Switzerland
- 5European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL‐EBI) Wellcome Trust Genome Campus, Cambridge, UK
- 6MRC Human Genetics Unit, IGMM, University of Edinburgh, Edinburgh, UK
- ↵*
Corresponding author. Tel: +44 131 650 7092; E‐mail: d.tollervey{at}ed.ac.uk
Corresponding author. Tel: +44 131 651 8628; E‐mail: gkudla{at}gmail.com
Corresponding author. Tel: +44 131 650 5136; E‐mail: gsanguin{at}inf.ed.ac.uk
A new technique for transcriptome‐wide mapping of RNAPII carrying the five types of CTD phosphorylation is presented. Distinct modification states associated with initiating, early and late elongating RNAPII are identified using a hidden Markov model.
Synopsis
A new technique for transcriptome‐wide mapping of RNAPII carrying the five types of CTD phosphorylation is presented. Distinct modification states associated with initiating, early and late elongating RNAPII are identified using a hidden Markov model.
Multiple modified forms of RNAPII can be mapped with nucleotide resolution.
Machine learning can be used to extract biological insights from these datasets.
Initiating RNAPII is associated with a distinct, surveillance‐prone state.
Unstable ncRNAs fail to exit this state, potentially linked to rapid degradation.
Mol Syst Biol. (2016) 12: 874
- Received February 8, 2016.
- Revision received May 13, 2016.
- Accepted May 18, 2016.
- © 2016 The Authors. Published under the terms of the CC BY 4.0 license
This is an open access article under the terms of the Creative Commons Attribution 4.0 License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Genomics, Systems Genetics & Functional Genomics
Highlights of research recently published in Molecular Systems Biology:
- Allelic expression mapping across cellular lineages
- Genome annotation by bidirectional HMMs
- Defining a Minimal Genome
- Natural network involved in autism
- Heritability of human plasma proteins
- Negative feedback buffers regulatory variants
- Genetic variation impacting antisense transcription
- Bar-ChIP for high-throughput chromatin profiling