---
_id: '1358'
abstract:
- lang: eng
text: 'Gene regulation relies on the specificity of transcription factor (TF)–DNA
interactions. Limited specificity may lead to crosstalk: a regulatory state in
which a gene is either incorrectly activated due to noncognate TF–DNA interactions
or remains erroneously inactive. As each TF can have numerous interactions with
noncognate cis-regulatory elements, crosstalk is inherently a global problem,
yet has previously not been studied as such. We construct a theoretical framework
to analyse the effects of global crosstalk on gene regulation. We find that crosstalk
presents a significant challenge for organisms with low-specificity TFs, such
as metazoans. Crosstalk is not easily mitigated by known regulatory schemes acting
at equilibrium, including variants of cooperativity and combinatorial regulation.
Our results suggest that crosstalk imposes a previously unexplored global constraint
on the functioning and evolution of regulatory networks, which is qualitatively
distinct from the known constraints that act at the level of individual gene regulatory
elements.'
article_number: '12307'
article_processing_charge: No
author:
- first_name: Tamar
full_name: Friedlander, Tamar
id: 36A5845C-F248-11E8-B48F-1D18A9856A87
last_name: Friedlander
- first_name: Roshan
full_name: Prizak, Roshan
id: 4456104E-F248-11E8-B48F-1D18A9856A87
last_name: Prizak
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
citation:
ama: Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. Intrinsic limits to
gene regulation by global crosstalk. Nature Communications. 2016;7. doi:10.1038/ncomms12307
apa: Friedlander, T., Prizak, R., Guet, C. C., Barton, N. H., & Tkačik, G. (2016).
Intrinsic limits to gene regulation by global crosstalk. Nature Communications.
Nature Publishing Group. https://doi.org/10.1038/ncomms12307
chicago: Friedlander, Tamar, Roshan Prizak, Calin C Guet, Nicholas H Barton, and
Gašper Tkačik. “Intrinsic Limits to Gene Regulation by Global Crosstalk.” Nature
Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms12307.
ieee: T. Friedlander, R. Prizak, C. C. Guet, N. H. Barton, and G. Tkačik, “Intrinsic
limits to gene regulation by global crosstalk,” Nature Communications,
vol. 7. Nature Publishing Group, 2016.
ista: Friedlander T, Prizak R, Guet CC, Barton NH, Tkačik G. 2016. Intrinsic limits
to gene regulation by global crosstalk. Nature Communications. 7, 12307.
mla: Friedlander, Tamar, et al. “Intrinsic Limits to Gene Regulation by Global Crosstalk.”
Nature Communications, vol. 7, 12307, Nature Publishing Group, 2016, doi:10.1038/ncomms12307.
short: T. Friedlander, R. Prizak, C.C. Guet, N.H. Barton, G. Tkačik, Nature Communications
7 (2016).
corr_author: '1'
date_created: 2018-12-11T11:51:34Z
date_published: 2016-08-04T00:00:00Z
date_updated: 2026-04-08T13:54:24Z
day: '04'
ddc:
- '576'
department:
- _id: GaTk
- _id: NiBa
- _id: CaGu
doi: 10.1038/ncomms12307
ec_funded: 1
external_id:
isi:
- '000380858400001'
file:
- access_level: open_access
checksum: fe3f3a1526d180b29fe691ab11435b78
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:01Z
date_updated: 2020-07-14T12:44:46Z
file_id: '4919'
file_name: IST-2016-627-v1+1_ncomms12307.pdf
file_size: 861805
relation: main_file
- access_level: open_access
checksum: 164864a1a675f3ad80e9917c27aba07f
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:12:02Z
date_updated: 2020-07-14T12:44:46Z
file_id: '4920'
file_name: IST-2016-627-v1+2_ncomms12307-s1.pdf
file_size: 1084703
relation: main_file
file_date_updated: 2020-07-14T12:44:46Z
fulldoi: https://doi.org/10.1038/ncomms12307
has_accepted_license: '1'
intvolume: ' 7'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '08'
oa: 1
oa_version: Published Version
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Nature Communications
publication_status: published
publisher: Nature Publishing Group
publist_id: '5887'
pubrep_id: '627'
quality_controlled: '1'
related_material:
record:
- id: '6071'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Intrinsic limits to gene regulation by global crosstalk
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 7
year: '2016'
...
---
_id: '1359'
abstract:
- lang: eng
text: "The role of gene interactions in the evolutionary process has long\r\nbeen
controversial. Although some argue that they are not of\r\nimportance, because
most variation is additive, others claim that\r\ntheir effect in the long term
can be substantial. Here, we focus on\r\nthe long-term effects of genetic interactions
under directional\r\nselection assuming no mutation or dominance, and that epistasis
is\r\nsymmetrical overall. We ask by how much the mean of a complex\r\ntrait can
be increased by selection and analyze two extreme\r\nregimes, in which either
drift or selection dominate the dynamics\r\nof allele frequencies. In both scenarios,
epistatic interactions affect\r\nthe long-term response to selection by modulating
the additive\r\ngenetic variance. When drift dominates, we extend Robertson\r\n’\r\ns\r\n[Robertson
A (1960)\r\nProc R Soc Lond B Biol Sci\r\n153(951):234\r\n−\r\n249]\r\nargument
to show that, for any form of epistasis, the total response\r\nof a haploid population
is proportional to the initial total genotypic\r\nvariance. In contrast, the total
response of a diploid population is\r\nincreased by epistasis, for a given initial
genotypic variance. When\r\nselection dominates, we show that the total selection
response can\r\nonly be increased by epistasis when s\r\nome initially deleterious
alleles\r\nbecome favored as the genetic background changes. We find a sim-\r\nple
approximation for this effect and show that, in this regime, it is\r\nthe structure
of the genotype - phenotype map that matters and not\r\nthe variance components
of the population."
article_processing_charge: No
article_type: original
author:
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
citation:
ama: Paixao T, Barton NH. The effect of gene interactions on the long-term response
to selection. PNAS. 2016;113(16):4422-4427. doi:10.1073/pnas.1518830113
apa: Paixao, T., & Barton, N. H. (2016). The effect of gene interactions on
the long-term response to selection. PNAS. National Academy of Sciences.
https://doi.org/10.1073/pnas.1518830113
chicago: Paixao, Tiago, and Nicholas H Barton. “The Effect of Gene Interactions
on the Long-Term Response to Selection.” PNAS. National Academy of Sciences,
2016. https://doi.org/10.1073/pnas.1518830113.
ieee: T. Paixao and N. H. Barton, “The effect of gene interactions on the long-term
response to selection,” PNAS, vol. 113, no. 16. National Academy of Sciences,
pp. 4422–4427, 2016.
ista: Paixao T, Barton NH. 2016. The effect of gene interactions on the long-term
response to selection. PNAS. 113(16), 4422–4427.
mla: Paixao, Tiago, and Nicholas H. Barton. “The Effect of Gene Interactions on
the Long-Term Response to Selection.” PNAS, vol. 113, no. 16, National
Academy of Sciences, 2016, pp. 4422–27, doi:10.1073/pnas.1518830113.
short: T. Paixao, N.H. Barton, PNAS 113 (2016) 4422–4427.
corr_author: '1'
date_created: 2018-12-11T11:51:34Z
date_published: 2016-04-19T00:00:00Z
date_updated: 2026-06-18T17:31:02Z
day: '19'
ddc:
- '570'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1073/pnas.1518830113
ec_funded: 1
external_id:
isi:
- '000374393800056'
pmid:
- '27044080'
fulldoi: https://doi.org/10.1073/pnas.1518830113
intvolume: ' 113'
isi: 1
issue: '16'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4843425/
month: '04'
oa: 1
oa_version: Published Version
page: 4422 - 4427
pmid: 1
project:
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: PNAS
publication_status: published
publisher: National Academy of Sciences
publist_id: '5886'
quality_controlled: '1'
scopus_import: '1'
status: public
title: The effect of gene interactions on the long-term response to selection
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 113
year: '2016'
...
---
_id: '1427'
abstract:
- lang: eng
text: Changes in gene expression are an important mode of evolution; however, the
proximate mechanism of these changes is poorly understood. In particular, little
is known about the effects of mutations within cis binding sites for transcription
factors, or the nature of epistatic interactions between these mutations. Here,
we tested the effects of single and double mutants in two cis binding sites involved
in the transcriptional regulation of the Escherichia coli araBAD operon, a component
of arabinose metabolism, using a synthetic system. This system decouples transcriptional
control from any posttranslational effects on fitness, allowing a precise estimate
of the effect of single and double mutations, and hence epistasis, on gene expression.
We found that epistatic interactions between mutations in the araBAD cis-regulatory
element are common, and that the predominant form of epistasis is negative. The
magnitude of the interactions depended on whether the mutations are located in
the same or in different operator sites. Importantly, these epistatic interactions
were dependent on the presence of arabinose, a native inducer of the araBAD operon
in vivo, with some interactions changing in sign (e.g., from negative to positive)
in its presence. This study thus reveals that mutations in even relatively simple
cis-regulatory elements interact in complex ways such that selection on the level
of gene expression in one environment might perturb regulation in the other environment
in an unpredictable and uncorrelated manner.
article_processing_charge: No
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Claudia
full_name: Igler, Claudia
id: 46613666-F248-11E8-B48F-1D18A9856A87
last_name: Igler
- first_name: Anaisa
full_name: Moreno, Anaisa
last_name: Moreno
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
citation:
ama: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. Epistatic interactions
in the arabinose cis-regulatory element. Molecular Biology and Evolution.
2016;33(3):761-769. doi:10.1093/molbev/msv269
apa: Lagator, M., Igler, C., Moreno, A., Guet, C. C., & Bollback, J. P. (2016).
Epistatic interactions in the arabinose cis-regulatory element. Molecular Biology
and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv269
chicago: Lagator, Mato, Claudia Igler, Anaisa Moreno, Calin C Guet, and Jonathan
P Bollback. “Epistatic Interactions in the Arabinose Cis-Regulatory Element.”
Molecular Biology and Evolution. Oxford University Press, 2016. https://doi.org/10.1093/molbev/msv269.
ieee: M. Lagator, C. Igler, A. Moreno, C. C. Guet, and J. P. Bollback, “Epistatic
interactions in the arabinose cis-regulatory element,” Molecular Biology and
Evolution, vol. 33, no. 3. Oxford University Press, pp. 761–769, 2016.
ista: Lagator M, Igler C, Moreno A, Guet CC, Bollback JP. 2016. Epistatic interactions
in the arabinose cis-regulatory element. Molecular Biology and Evolution. 33(3),
761–769.
mla: Lagator, Mato, et al. “Epistatic Interactions in the Arabinose Cis-Regulatory
Element.” Molecular Biology and Evolution, vol. 33, no. 3, Oxford University
Press, 2016, pp. 761–69, doi:10.1093/molbev/msv269.
short: M. Lagator, C. Igler, A. Moreno, C.C. Guet, J.P. Bollback, Molecular Biology
and Evolution 33 (2016) 761–769.
corr_author: '1'
date_created: 2018-12-11T11:51:57Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2025-09-18T14:11:47Z
day: '01'
ddc:
- '570'
- '576'
department:
- _id: CaGu
- _id: JoBo
doi: 10.1093/molbev/msv269
ec_funded: 1
external_id:
isi:
- '000371219500014'
file:
- access_level: open_access
checksum: 1f456ce1d2aa2f67176a1709f9702ecf
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:09:27Z
date_updated: 2020-07-14T12:44:53Z
file_id: '4751'
file_name: IST-2016-588-v1+1_Mol_Biol_Evol-2016-Lagator-761-9.pdf
file_size: 648115
relation: main_file
file_date_updated: 2020-07-14T12:44:53Z
fulldoi: https://doi.org/10.1093/molbev/msv269
has_accepted_license: '1'
intvolume: ' 33'
isi: 1
issue: '3'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: 761 - 769
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication: Molecular Biology and Evolution
publication_status: published
publisher: Oxford University Press
publist_id: '5772'
pubrep_id: '588'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Epistatic interactions in the arabinose cis-regulatory element
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 33
year: '2016'
...
---
_id: '1524'
abstract:
- lang: eng
text: "When designing genetic circuits, the typical primitives used in major existing
modelling formalisms are gene interaction graphs, where edges between genes denote
either an activation or inhibition relation. However, when designing experiments,
it is important to be precise about the low-level mechanistic details as to how
each such relation is implemented. The rule-based modelling language Kappa allows
to unambiguously specify mechanistic details such as DNA binding sites, dimerisation
of transcription factors, or co-operative interactions. Such a detailed description
comes with complexity and computationally costly executions. We propose a general
method for automatically transforming a rule-based program, by eliminating intermediate
species and adjusting the rate constants accordingly. To the best of our knowledge,
we show the first automated reduction of rule-based models based on equilibrium
approximations.\r\nOur algorithm is an adaptation of an existing algorithm, which
was designed for reducing reaction-based programs; our version of the algorithm
scans the rule-based Kappa model in search for those interaction patterns known
to be amenable to equilibrium approximations (e.g. Michaelis-Menten scheme). Additional
checks are then performed in order to verify if the reduction is meaningful in
the context of the full model. The reduced model is efficiently obtained by static
inspection over the rule-set. The tool is tested on a detailed rule-based model
of a λ-phage switch, which lists 92 rules and 13 agents. The reduced model has
11 rules and 5 agents, and provides a dramatic reduction in simulation time of
several orders of magnitude."
acknowledgement: This research was supported by the People Programme (Marie Curie
Actions) of the European Union’s Seventh Framework Programme (FP7/2007-2013) under
REA grant agreement no. 291734, and the SNSF Early Postdoc.Mobility Fellowship,
the grant number P2EZP2_148797.
alternative_title:
- LNCS
article_processing_charge: No
arxiv: 1
author:
- first_name: Andreea
full_name: Beica, Andreea
last_name: Beica
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
citation:
ama: 'Beica A, Guet CC, Petrov T. Efficient reduction of kappa models by static
inspection of the rule-set. In: Vol 9271. Springer; 2016:173-191. doi:10.1007/978-3-319-26916-0_10'
apa: 'Beica, A., Guet, C. C., & Petrov, T. (2016). Efficient reduction of kappa
models by static inspection of the rule-set (Vol. 9271, pp. 173–191). Presented
at the HSB: Hybrid Systems Biology, Madrid, Spain: Springer. https://doi.org/10.1007/978-3-319-26916-0_10'
chicago: Beica, Andreea, Calin C Guet, and Tatjana Petrov. “Efficient Reduction
of Kappa Models by Static Inspection of the Rule-Set,” 9271:173–91. Springer,
2016. https://doi.org/10.1007/978-3-319-26916-0_10.
ieee: 'A. Beica, C. C. Guet, and T. Petrov, “Efficient reduction of kappa models
by static inspection of the rule-set,” presented at the HSB: Hybrid Systems Biology,
Madrid, Spain, 2016, vol. 9271, pp. 173–191.'
ista: 'Beica A, Guet CC, Petrov T. 2016. Efficient reduction of kappa models by
static inspection of the rule-set. HSB: Hybrid Systems Biology, LNCS, vol. 9271,
173–191.'
mla: Beica, Andreea, et al. Efficient Reduction of Kappa Models by Static Inspection
of the Rule-Set. Vol. 9271, Springer, 2016, pp. 173–91, doi:10.1007/978-3-319-26916-0_10.
short: A. Beica, C.C. Guet, T. Petrov, in:, Springer, 2016, pp. 173–191.
conference:
end_date: 2015-09-05
location: Madrid, Spain
name: 'HSB: Hybrid Systems Biology'
start_date: 2015-09-04
corr_author: '1'
date_created: 2018-12-11T11:52:31Z
date_published: 2016-01-10T00:00:00Z
date_updated: 2025-06-04T12:06:27Z
day: '10'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1007/978-3-319-26916-0_10
ec_funded: 1
external_id:
arxiv:
- '1501.00440'
fulldoi: https://doi.org/10.1007/978-3-319-26916-0_10
intvolume: ' 9271'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1501.00440
month: '01'
oa: 1
oa_version: Preprint
page: 173 - 191
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication_status: published
publisher: Springer
publist_id: '5649'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Efficient reduction of kappa models by static inspection of the rule-set
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9271
year: '2016'
...
---
DOAJ_listed: '1'
OA_place: publisher
OA_type: gold
_id: '5749'
abstract:
- lang: eng
text: Parasitism creates selection for resistance mechanisms in host populations
and is hypothesized to promote increased host evolvability. However, the influence
of these traits on host evolution when parasites are no longer present is unclear.
We used experimental evolution and whole-genome sequencing of Escherichia coli
to determine the effects of past and present exposure to parasitic viruses (phages)
on the spread of mutator alleles, resistance, and bacterial competitive fitness.
We found that mutator alleles spread rapidly during adaptation to any of four
different phage species, and this pattern was even more pronounced with multiple
phages present simultaneously. However, hypermutability did not detectably accelerate
adaptation in the absence of phages and recovery of fitness costs associated with
resistance. Several lineages evolved phage resistance through elevated mucoidy,
and during subsequent evolution in phage-free conditions they rapidly reverted
to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this
phenotypic reversion was achieved by additional genetic changes rather than by
genotypic reversion of the initial resistance mutations. Insertion sequence (IS)
elements played a key role in both the acquisition of resistance and adaptation
in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions
were not more frequent in mutator lineages. Our results provide a genetic explanation
for rapid reversion of mucoidy, a phenotype observed in other bacterial species
including human pathogens. Moreover, this demonstrates that the types of genetic
change underlying adaptation to fitness costs, and consequently the impact of
evolvability mechanisms such as increased point-mutation rates, depend critically
on the mechanism of resistance.
acknowledgement: The authors thank three anonymous reviewers and the editor for helpful
comments on the manuscript, as well as Dominique Schneider for feedback on an earlier
draft, Jenna Gallie for lytic λ and Julien Capelle for T5 and T6. This work was
supported by the Swiss National Science Foundation (PZ00P3_148255 to A.H.) and an
EU Marie Curie PEOPLE Postdoctoral Fellowship for Career Development (FP7-PEOPLE-2012-IEF-331824
to S.W.).
article_processing_charge: No
article_type: original
author:
- first_name: Sébastien
full_name: Wielgoss, Sébastien
last_name: Wielgoss
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Anna M.
full_name: Bischofberger, Anna M.
last_name: Bischofberger
- first_name: Alex R.
full_name: Hall, Alex R.
last_name: Hall
citation:
ama: Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Adaptation to parasites
and costs of parasite resistance in mutator and nonmutator bacteria. Molecular
Biology and Evolution. 2016;33(3):770-782. doi:10.1093/molbev/msv270
apa: Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2016).
Adaptation to parasites and costs of parasite resistance in mutator and nonmutator
bacteria. Molecular Biology and Evolution. Oxford University Press. https://doi.org/10.1093/molbev/msv270
chicago: Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex
R. Hall. “Adaptation to Parasites and Costs of Parasite Resistance in Mutator
and Nonmutator Bacteria.” Molecular Biology and Evolution. Oxford University
Press, 2016. https://doi.org/10.1093/molbev/msv270.
ieee: S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Adaptation
to parasites and costs of parasite resistance in mutator and nonmutator bacteria,”
Molecular Biology and Evolution, vol. 33, no. 3. Oxford University Press,
pp. 770–782, 2016.
ista: Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2016. Adaptation to parasites
and costs of parasite resistance in mutator and nonmutator bacteria. Molecular
Biology and Evolution. 33(3), 770–782.
mla: Wielgoss, Sébastien, et al. “Adaptation to Parasites and Costs of Parasite
Resistance in Mutator and Nonmutator Bacteria.” Molecular Biology and Evolution,
vol. 33, no. 3, Oxford University Press, 2016, pp. 770–82, doi:10.1093/molbev/msv270.
short: S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, Molecular Biology
and Evolution 33 (2016) 770–782.
date_created: 2018-12-18T13:18:10Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2026-04-29T05:57:02Z
day: '01'
ddc:
- '576'
department:
- _id: CaGu
doi: 10.1093/molbev/msv270
external_id:
isi:
- '000371219500015'
pmid:
- '26609077'
file:
- access_level: open_access
checksum: 47d9010690b6c5c17f2ac830cc63ac5c
content_type: application/pdf
creator: dernst
date_created: 2018-12-18T13:21:45Z
date_updated: 2020-07-14T12:47:10Z
file_id: '5750'
file_name: 2016_MolBiolEvol_Wielgoss.pdf
file_size: 634037
relation: main_file
file_date_updated: 2020-07-14T12:47:10Z
fulldoi: https://doi.org/10.1093/molbev/msv270
has_accepted_license: '1'
intvolume: ' 33'
isi: 1
issue: '3'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
month: '03'
oa: 1
oa_version: Published Version
page: 770-782
pmid: 1
publication: Molecular Biology and Evolution
publication_identifier:
eissn:
- 1537-1719
issn:
- 0737-4038
publication_status: published
publisher: Oxford University Press
pubrep_id: '587'
quality_controlled: '1'
related_material:
record:
- id: '9719'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Adaptation to parasites and costs of parasite resistance in mutator and nonmutator
bacteria
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 33
year: '2016'
...
---
_id: '1008'
abstract:
- lang: eng
text: Feedback loops in biological networks, among others, enable differentiation
and cell cycle progression, and increase robustness in signal transduction. In
natural networks, feedback loops are often complex and intertwined, making it
challenging to identify which loops are mainly responsible for an observed behavior.
However, minimal synthetic replicas could allow for such identification. Here,
we engineered a synthetic permease-inducer-repressor system in Saccharomyces cerevisiae
to analyze if a transport-mediated positive feedback loop could be a core mechanism
for the switch-like behavior in the regulation of metabolic gene networks such
as the S. cerevisiae GAL system or the Escherichia coli lac operon. We characterized
the synthetic circuit using deterministic and stochastic mathematical models.
Similar to its natural counterparts, our synthetic system shows bistable and hysteretic
behavior, and the inducer concentration range for bistability as well as the switching
rates between the two stable states depend on the repressor concentration. Our
results indicate that a generic permease–inducer–repressor circuit with a single
feedback loop is sufficient to explain the experimentally observed bistable behavior
of the natural systems. We anticipate that the approach of reimplementing natural
systems with orthogonal parts to identify crucial network components is applicable
to other natural systems such as signaling pathways.
acknowledgement: We thank Julio Polaina (Instituto de Agroqu ı ́ mica y Tecnolog ı
́ a de Alimentos, C.S.I.C., Paterna, Spain) for the gift of plasmid pMR4, Gregor
W. Schmidt for provision of and support with the micro fl uidic device, Markus Du
̈ rr for the cell tracking R script, and Lukas Widmer for the script for MEIGO using
“ parfor ” in MATLAB. We acknowledge the members of the Stelling group for discussions,
comments, and support.
article_processing_charge: No
author:
- first_name: Robert
full_name: Gnügge, Robert
last_name: Gnügge
- first_name: Lekshmi
full_name: Dharmarajan, Lekshmi
last_name: Dharmarajan
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Jörg
full_name: Stelling, Jörg
last_name: Stelling
citation:
ama: Gnügge R, Dharmarajan L, Lang M, Stelling J. An orthogonal permease–inducer–repressor
feedback loop shows bistability. ACS Synthetic Biology. 2016;5(10):1098-1107.
doi:10.1021/acssynbio.6b00013
apa: Gnügge, R., Dharmarajan, L., Lang, M., & Stelling, J. (2016). An orthogonal
permease–inducer–repressor feedback loop shows bistability. ACS Synthetic Biology.
American Chemical Society. https://doi.org/10.1021/acssynbio.6b00013
chicago: Gnügge, Robert, Lekshmi Dharmarajan, Moritz Lang, and Jörg Stelling. “An
Orthogonal Permease–Inducer–Repressor Feedback Loop Shows Bistability.” ACS
Synthetic Biology. American Chemical Society, 2016. https://doi.org/10.1021/acssynbio.6b00013.
ieee: R. Gnügge, L. Dharmarajan, M. Lang, and J. Stelling, “An orthogonal permease–inducer–repressor
feedback loop shows bistability,” ACS Synthetic Biology, vol. 5, no. 10.
American Chemical Society, pp. 1098–1107, 2016.
ista: Gnügge R, Dharmarajan L, Lang M, Stelling J. 2016. An orthogonal permease–inducer–repressor
feedback loop shows bistability. ACS Synthetic Biology. 5(10), 1098–1107.
mla: Gnügge, Robert, et al. “An Orthogonal Permease–Inducer–Repressor Feedback Loop
Shows Bistability.” ACS Synthetic Biology, vol. 5, no. 10, American Chemical
Society, 2016, pp. 1098–107, doi:10.1021/acssynbio.6b00013.
short: R. Gnügge, L. Dharmarajan, M. Lang, J. Stelling, ACS Synthetic Biology 5
(2016) 1098–1107.
date_created: 2018-12-11T11:49:40Z
date_published: 2016-05-05T00:00:00Z
date_updated: 2025-09-22T14:20:45Z
day: '05'
department:
- _id: CaGu
doi: 10.1021/acssynbio.6b00013
external_id:
isi:
- '000386196100008'
fulldoi: https://doi.org/10.1021/acssynbio.6b00013
intvolume: ' 5'
isi: 1
issue: '10'
language:
- iso: eng
month: '05'
oa_version: None
page: 1098 - 1107
publication: ACS Synthetic Biology
publication_status: published
publisher: American Chemical Society
publist_id: '6390'
quality_controlled: '1'
status: public
title: An orthogonal permease–inducer–repressor feedback loop shows bistability
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 5
year: '2016'
...
---
_id: '9873'
article_processing_charge: No
author:
- first_name: Alex
full_name: Boehm, Alex
last_name: Boehm
- first_name: Markus
full_name: Arnoldini, Markus
last_name: Arnoldini
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Thomas
full_name: Röösli, Thomas
last_name: Röösli
- first_name: Colette
full_name: Bigosch, Colette
last_name: Bigosch
- first_name: Martin
full_name: Ackermann, Martin
last_name: Ackermann
citation:
ama: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. Quantification
of the growth rate reduction as a consequence of age-specific mortality. 2016.
doi:10.1371/journal.pgen.1005974.s015
apa: Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann,
M. (2016). Quantification of the growth rate reduction as a consequence of age-specific
mortality. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974.s015
chicago: Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette
Bigosch, and Martin Ackermann. “Quantification of the Growth Rate Reduction as
a Consequence of Age-Specific Mortality.” Public Library of Science, 2016. https://doi.org/10.1371/journal.pgen.1005974.s015.
ieee: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann,
“Quantification of the growth rate reduction as a consequence of age-specific
mortality.” Public Library of Science, 2016.
ista: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016.
Quantification of the growth rate reduction as a consequence of age-specific mortality,
Public Library of Science, 10.1371/journal.pgen.1005974.s015.
mla: Boehm, Alex, et al. Quantification of the Growth Rate Reduction as a Consequence
of Age-Specific Mortality. Public Library of Science, 2016, doi:10.1371/journal.pgen.1005974.s015.
short: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann,
(2016).
date_created: 2021-08-10T09:42:34Z
date_updated: 2025-09-22T09:10:03Z
day: '19'
department:
- _id: CaGu
doi: 10.1371/journal.pgen.1005974.s015
fulldoi: https://doi.org/10.1371/journal.pgen.1005974.s015
month: '04'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '1250'
relation: used_in_publication
status: public
status: public
title: Quantification of the growth rate reduction as a consequence of age-specific
mortality
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2016'
...
---
OA_place: repository
OA_type: green
_id: '1170'
abstract:
- lang: eng
text: The increasing complexity of dynamic models in systems and synthetic biology
poses computational challenges especially for the identification of model parameters.
While modularization of the corresponding optimization problems could help reduce
the “curse of dimensionality,” abundant feedback and crosstalk mechanisms prohibit
a simple decomposition of most biomolecular networks into subnetworks, or modules.
Drawing on ideas from network modularization and multiple-shooting optimization,
we present here a modular parameter identification approach that explicitly allows
for such interdependencies. Interfaces between our modules are given by the experimentally
measured molecular species. This definition allows deriving good (initial) estimates
for the inter-module communication directly from the experimental data. Given
these estimates, the states and parameter sensitivities of different modules can
be integrated independently. To achieve consistency between modules, we iteratively
adjust the estimates for inter-module communication while optimizing the parameters.
After convergence to an optimal parameter set---but not during earlier iterations---the
intermodule communication as well as the individual modules\' state dynamics agree
with the dynamics of the nonmodularized network. Our modular parameter identification
approach allows for easy parallelization; it can reduce the computational complexity
for larger networks and decrease the probability to converge to suboptimal local
minima. We demonstrate the algorithm\'s performance in parameter estimation for
two biomolecular networks, a synthetic genetic oscillator and a mammalian signaling
pathway.
article_processing_charge: No
article_type: original
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Jörg
full_name: Stelling, Jörg
last_name: Stelling
citation:
ama: Lang M, Stelling J. Modular parameter identification of biomolecular networks.
SIAM Journal on Scientific Computing. 2016;38(6):B988-B1008. doi:10.1137/15M103306X
apa: Lang, M., & Stelling, J. (2016). Modular parameter identification of biomolecular
networks. SIAM Journal on Scientific Computing. Society for Industrial
and Applied Mathematics. https://doi.org/10.1137/15M103306X
chicago: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular
Networks.” SIAM Journal on Scientific Computing. Society for Industrial
and Applied Mathematics, 2016. https://doi.org/10.1137/15M103306X.
ieee: M. Lang and J. Stelling, “Modular parameter identification of biomolecular
networks,” SIAM Journal on Scientific Computing, vol. 38, no. 6. Society
for Industrial and Applied Mathematics, pp. B988–B1008, 2016.
ista: Lang M, Stelling J. 2016. Modular parameter identification of biomolecular
networks. SIAM Journal on Scientific Computing. 38(6), B988–B1008.
mla: Lang, Moritz, and Jörg Stelling. “Modular Parameter Identification of Biomolecular
Networks.” SIAM Journal on Scientific Computing, vol. 38, no. 6, Society
for Industrial and Applied Mathematics, 2016, pp. B988–1008, doi:10.1137/15M103306X.
short: M. Lang, J. Stelling, SIAM Journal on Scientific Computing 38 (2016) B988–B1008.
corr_author: '1'
das_tickbox: '1'
date_created: 2018-12-11T11:50:31Z
date_published: 2016-11-15T00:00:00Z
date_updated: 2026-07-06T14:00:20Z
day: '15'
ddc:
- '003'
- '518'
- '570'
- '621'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1137/15M103306X
external_id:
isi:
- '000391853100010'
file:
- access_level: open_access
checksum: 781bc3ffd30b2dd65b7727c5a285fc78
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:41Z
date_updated: 2025-06-25T11:26:45Z
file_id: '5095'
file_name: IST-2017-811-v1+1_modular_parameter_identification.pdf
file_size: 871964
relation: main_file
file_date_updated: 2025-06-25T11:26:45Z
fulldoi: https://doi.org/10.1137/15M103306X
has_accepted_license: '1'
intvolume: ' 38'
isi: 1
issue: '6'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Submitted Version
page: B988 - B1008
publication: SIAM Journal on Scientific Computing
publication_status: published
publisher: Society for Industrial and Applied Mathematics
publist_id: '6186'
pubrep_id: '811'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Modular parameter identification of biomolecular networks
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 38
year: '2016'
...
---
_id: '1430'
abstract:
- lang: eng
text: Evolutionary algorithms (EAs) form a popular optimisation paradigm inspired
by natural evolution. In recent years the field of evolutionary computation has
developed a rigorous analytical theory to analyse their runtime on many illustrative
problems. Here we apply this theory to a simple model of natural evolution. In
the Strong Selection Weak Mutation (SSWM) evolutionary regime the time between
occurrence of new mutations is much longer than the time it takes for a new beneficial
mutation to take over the population. In this situation, the population only contains
copies of one genotype and evolution can be modelled as a (1+1)-type process where
the probability of accepting a new genotype (improvements or worsenings) depends
on the change in fitness. We present an initial runtime analysis of SSWM, quantifying
its performance for various parameters and investigating differences to the (1+1)
EA. We show that SSWM can have a moderate advantage over the (1+1) EA at crossing
fitness valleys and study an example where SSWM outperforms the (1+1) EA by taking
advantage of information on the fitness gradient.
article_processing_charge: No
arxiv: 1
author:
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Dirk
full_name: Sudholt, Dirk
last_name: Sudholt
- first_name: Jorge
full_name: Heredia, Jorge
last_name: Heredia
- first_name: Barbora
full_name: Trubenova, Barbora
id: 42302D54-F248-11E8-B48F-1D18A9856A87
last_name: Trubenova
orcid: 0000-0002-6873-2967
citation:
ama: 'Paixao T, Sudholt D, Heredia J, Trubenova B. First steps towards a runtime
comparison of natural and artificial evolution. In: Proceedings of the 2015
Annual Conference on Genetic and Evolutionary Computation. ACM; 2015:1455-1462.
doi:10.1145/2739480.2754758'
apa: 'Paixao, T., Sudholt, D., Heredia, J., & Trubenova, B. (2015). First steps
towards a runtime comparison of natural and artificial evolution. In Proceedings
of the 2015 Annual Conference on Genetic and Evolutionary Computation (pp.
1455–1462). Madrid, Spain: ACM. https://doi.org/10.1145/2739480.2754758'
chicago: Paixao, Tiago, Dirk Sudholt, Jorge Heredia, and Barbora Trubenova. “First
Steps towards a Runtime Comparison of Natural and Artificial Evolution.” In Proceedings
of the 2015 Annual Conference on Genetic and Evolutionary Computation, 1455–62.
ACM, 2015. https://doi.org/10.1145/2739480.2754758.
ieee: T. Paixao, D. Sudholt, J. Heredia, and B. Trubenova, “First steps towards
a runtime comparison of natural and artificial evolution,” in Proceedings of
the 2015 Annual Conference on Genetic and Evolutionary Computation, Madrid,
Spain, 2015, pp. 1455–1462.
ista: 'Paixao T, Sudholt D, Heredia J, Trubenova B. 2015. First steps towards a
runtime comparison of natural and artificial evolution. Proceedings of the 2015
Annual Conference on Genetic and Evolutionary Computation. GECCO: Genetic and
evolutionary computation conference, 1455–1462.'
mla: Paixao, Tiago, et al. “First Steps towards a Runtime Comparison of Natural
and Artificial Evolution.” Proceedings of the 2015 Annual Conference on Genetic
and Evolutionary Computation, ACM, 2015, pp. 1455–62, doi:10.1145/2739480.2754758.
short: T. Paixao, D. Sudholt, J. Heredia, B. Trubenova, in:, Proceedings of the
2015 Annual Conference on Genetic and Evolutionary Computation, ACM, 2015, pp.
1455–1462.
conference:
end_date: 2015-07-15
location: Madrid, Spain
name: 'GECCO: Genetic and evolutionary computation conference'
start_date: 2015-07-11
date_created: 2018-12-11T11:51:58Z
date_published: 2015-07-11T00:00:00Z
date_updated: 2025-09-23T08:50:33Z
day: '11'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1145/2739480.2754758
ec_funded: 1
external_id:
arxiv:
- '1504.06260'
isi:
- '000358795700182'
fulldoi: https://doi.org/10.1145/2739480.2754758
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1504.06260
month: '07'
oa: 1
oa_version: Preprint
page: 1455 - 1462
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
publication: Proceedings of the 2015 Annual Conference on Genetic and Evolutionary
Computation
publication_status: published
publisher: ACM
publist_id: '5768'
quality_controlled: '1'
scopus_import: '1'
status: public
title: First steps towards a runtime comparison of natural and artificial evolution
type: conference
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
year: '2015'
...
---
_id: '9712'
article_processing_charge: No
author:
- first_name: Murat
full_name: Tugrul, Murat
id: 37C323C6-F248-11E8-B48F-1D18A9856A87
last_name: Tugrul
orcid: 0000-0002-8523-0758
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Tugrul M, Paixao T, Barton NH, Tkačik G. Other fitness models for comparison
& for interacting TFBSs. 2015. doi:10.1371/journal.pgen.1005639.s001
apa: Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Other fitness
models for comparison & for interacting TFBSs. Public Library of Science.
https://doi.org/10.1371/journal.pgen.1005639.s001
chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Other
Fitness Models for Comparison & for Interacting TFBSs.” Public Library of
Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.s001.
ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Other fitness models for
comparison & for interacting TFBSs.” Public Library of Science, 2015.
ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Other fitness models for comparison
& for interacting TFBSs, Public Library of Science, 10.1371/journal.pgen.1005639.s001.
mla: Tugrul, Murat, et al. Other Fitness Models for Comparison & for Interacting
TFBSs. Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.s001.
short: M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, (2015).
date_created: 2021-07-23T12:00:37Z
date_published: 2015-11-06T00:00:00Z
date_updated: 2025-09-23T08:31:14Z
day: '06'
department:
- _id: NiBa
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pgen.1005639.s001
fulldoi: https://doi.org/10.1371/journal.pgen.1005639.s001
month: '11'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '1666'
relation: used_in_publication
status: public
status: public
title: Other fitness models for comparison & for interacting TFBSs
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2015'
...
---
_id: '9719'
abstract:
- lang: eng
text: Parasitism creates selection for resistance mechanisms in host populations
and is hypothesized to promote increased host evolvability. However, the influence
of these traits on host evolution when parasites are no longer present is unclear.
We used experimental evolution and whole-genome sequencing of Escherichia coli
to determine the effects of past and present exposure to parasitic viruses (phages)
on the spread of mutator alleles, resistance, and bacterial competitive fitness.
We found that mutator alleles spread rapidly during adaptation to any of four
different phage species, and this pattern was even more pronounced with multiple
phages present simultaneously. However, hypermutability did not detectably accelerate
adaptation in the absence of phages and recovery of fitness costs associated with
resistance. Several lineages evolved phage resistance through elevated mucoidy,
and during subsequent evolution in phage-free conditions they rapidly reverted
to nonmucoid, phage-susceptible phenotypes. Genome sequencing revealed that this
phenotypic reversion was achieved by additional genetic changes rather than by
genotypic reversion of the initial resistance mutations. Insertion sequence (IS)
elements played a key role in both the acquisition of resistance and adaptation
in the absence of parasites; unlike single nucleotide polymorphisms, IS insertions
were not more frequent in mutator lineages. Our results provide a genetic explanation
for rapid reversion of mucoidy, a phenotype observed in other bacterial species
including human pathogens. Moreover, this demonstrates that the types of genetic
change underlying adaptation to fitness costs, and consequently the impact of
evolvability mechanisms such as increased point-mutation rates, depend critically
on the mechanism of resistance.
article_processing_charge: No
author:
- first_name: Sébastien
full_name: Wielgoss, Sébastien
last_name: Wielgoss
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Anna M.
full_name: Bischofberger, Anna M.
last_name: Bischofberger
- first_name: Alex R.
full_name: Hall, Alex R.
last_name: Hall
citation:
ama: 'Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. Data from: Adaptation
to parasites and costs of parasite resistance in mutator and non-mutator bacteria.
2015. doi:10.5061/dryad.cj910'
apa: 'Wielgoss, S., Bergmiller, T., Bischofberger, A. M., & Hall, A. R. (2015).
Data from: Adaptation to parasites and costs of parasite resistance in mutator
and non-mutator bacteria. Dryad. https://doi.org/10.5061/dryad.cj910'
chicago: 'Wielgoss, Sébastien, Tobias Bergmiller, Anna M. Bischofberger, and Alex
R. Hall. “Data from: Adaptation to Parasites and Costs of Parasite Resistance
in Mutator and Non-Mutator Bacteria.” Dryad, 2015. https://doi.org/10.5061/dryad.cj910.'
ieee: 'S. Wielgoss, T. Bergmiller, A. M. Bischofberger, and A. R. Hall, “Data from:
Adaptation to parasites and costs of parasite resistance in mutator and non-mutator
bacteria.” Dryad, 2015.'
ista: 'Wielgoss S, Bergmiller T, Bischofberger AM, Hall AR. 2015. Data from: Adaptation
to parasites and costs of parasite resistance in mutator and non-mutator bacteria,
Dryad, 10.5061/dryad.cj910.'
mla: 'Wielgoss, Sébastien, et al. Data from: Adaptation to Parasites and Costs
of Parasite Resistance in Mutator and Non-Mutator Bacteria. Dryad, 2015, doi:10.5061/dryad.cj910.'
short: S. Wielgoss, T. Bergmiller, A.M. Bischofberger, A.R. Hall, (2015).
date_created: 2021-07-26T08:44:04Z
date_published: 2015-12-21T00:00:00Z
date_updated: 2026-04-29T05:57:01Z
day: '21'
department:
- _id: CaGu
doi: 10.5061/dryad.cj910
fulldoi: https://doi.org/10.5061/dryad.cj910
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.cj910
month: '12'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
record:
- id: '5749'
relation: used_in_publication
status: public
status: public
title: 'Data from: Adaptation to parasites and costs of parasite resistance in mutator
and non-mutator bacteria'
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2015'
...
---
_id: '1835'
abstract:
- lang: eng
text: The behaviour of gene regulatory networks (GRNs) is typically analysed using
simulation-based statistical testing-like methods. In this paper, we demonstrate
that we can replace this approach by a formal verification-like method that gives
higher assurance and scalability. We focus on Wagner’s weighted GRN model with
varying weights, which is used in evolutionary biology. In the model, weight parameters
represent the gene interaction strength that may change due to genetic mutations.
For a property of interest, we synthesise the constraints over the parameter space
that represent the set of GRNs satisfying the property. We experimentally show
that our parameter synthesis procedure computes the mutational robustness of GRNs
–an important problem of interest in evolutionary biology– more efficiently than
the classical simulation method. We specify the property in linear temporal logics.
We employ symbolic bounded model checking and SMT solving to compute the space
of GRNs that satisfy the property, which amounts to synthesizing a set of linear
constraints on the weights.
acknowledgement: "SNSF Early Postdoc.Mobility Fellowship, the grant number P2EZP2
148797.\r\n"
alternative_title:
- LNCS
article_processing_charge: No
arxiv: 1
author:
- first_name: Mirco
full_name: Giacobbe, Mirco
id: 3444EA5E-F248-11E8-B48F-1D18A9856A87
last_name: Giacobbe
orcid: 0000-0001-8180-0904
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
- first_name: Ashutosh
full_name: Gupta, Ashutosh
id: 335E5684-F248-11E8-B48F-1D18A9856A87
last_name: Gupta
- first_name: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000−0002−2985−7724
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
citation:
ama: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. Model checking
gene regulatory networks. 2015;9035:469-483. doi:10.1007/978-3-662-46681-0_47
apa: 'Giacobbe, M., Guet, C. C., Gupta, A., Henzinger, T. A., Paixao, T., &
Petrov, T. (2015). Model checking gene regulatory networks. Presented at the TACAS:
Tools and Algorithms for the Construction and Analysis of Systems, London, United
Kingdom: Springer. https://doi.org/10.1007/978-3-662-46681-0_47'
chicago: Giacobbe, Mirco, Calin C Guet, Ashutosh Gupta, Thomas A Henzinger, Tiago
Paixao, and Tatjana Petrov. “Model Checking Gene Regulatory Networks.” Lecture
Notes in Computer Science. Springer, 2015. https://doi.org/10.1007/978-3-662-46681-0_47.
ieee: M. Giacobbe, C. C. Guet, A. Gupta, T. A. Henzinger, T. Paixao, and T. Petrov,
“Model checking gene regulatory networks,” vol. 9035. Springer, pp. 469–483, 2015.
ista: Giacobbe M, Guet CC, Gupta A, Henzinger TA, Paixao T, Petrov T. 2015. Model
checking gene regulatory networks. 9035, 469–483.
mla: Giacobbe, Mirco, et al. Model Checking Gene Regulatory Networks. Vol.
9035, Springer, 2015, pp. 469–83, doi:10.1007/978-3-662-46681-0_47.
short: M. Giacobbe, C.C. Guet, A. Gupta, T.A. Henzinger, T. Paixao, T. Petrov, 9035
(2015) 469–483.
conference:
end_date: 2015-04-18
location: London, United Kingdom
name: 'TACAS: Tools and Algorithms for the Construction and Analysis of Systems'
start_date: 2015-04-11
date_created: 2018-12-11T11:54:16Z
date_published: 2015-04-01T00:00:00Z
date_updated: 2025-07-10T11:50:42Z
day: '01'
department:
- _id: ToHe
- _id: CaGu
- _id: NiBa
doi: 10.1007/978-3-662-46681-0_47
ec_funded: 1
external_id:
arxiv:
- '1410.7704'
fulldoi: https://doi.org/10.1007/978-3-662-46681-0_47
intvolume: ' 9035'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1410.7704
month: '04'
oa: 1
oa_version: Preprint
page: 469 - 483
project:
- _id: 25EE3708-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '267989'
name: Quantitative Reactive Modeling
- _id: 25832EC2-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: S 11407_N23
name: Rigorous Systems Engineering
- _id: 25F42A32-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: Z211
name: Formal methods for the design and analysis of complex systems
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication_status: published
publisher: Springer
publist_id: '5267'
quality_controlled: '1'
related_material:
record:
- id: '1351'
relation: later_version
status: public
scopus_import: '1'
series_title: Lecture Notes in Computer Science
status: public
title: Model checking gene regulatory networks
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 9035
year: '2015'
...
---
_id: '1840'
abstract:
- lang: eng
text: In this paper, we present a method for reducing a regular, discrete-time Markov
chain (DTMC) to another DTMC with a given, typically much smaller number of states.
The cost of reduction is defined as the Kullback-Leibler divergence rate between
a projection of the original process through a partition function and a DTMC on
the correspondingly partitioned state space. Finding the reduced model with minimal
cost is computationally expensive, as it requires an exhaustive search among all
state space partitions, and an exact evaluation of the reduction cost for each
candidate partition. Our approach deals with the latter problem by minimizing
an upper bound on the reduction cost instead of minimizing the exact cost. The
proposed upper bound is easy to compute and it is tight if the original chain
is lumpable with respect to the partition. Then, we express the problem in the
form of information bottleneck optimization, and propose using the agglomerative
information bottleneck algorithm for searching a suboptimal partition greedily,
rather than exhaustively. The theory is illustrated with examples and one application
scenario in the context of modeling bio-molecular interactions.
acknowledgement: "This work was supported by the Austrian Research Association under
Project 06/12684, by the Swiss National Science Foundation (SNSF) under Grant PP00P2
128503/1, by the SystemsX.ch (the Swiss Inititative for Systems Biology), and by
a SNSF Early Postdoc.Mobility Fellowship grant P2EZP2_148797.\r\n"
article_processing_charge: No
arxiv: 1
author:
- first_name: Bernhard
full_name: Geiger, Bernhard
last_name: Geiger
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
- first_name: Gernot
full_name: Kubin, Gernot
last_name: Kubin
- first_name: Heinz
full_name: Koeppl, Heinz
last_name: Koeppl
citation:
ama: Geiger B, Petrov T, Kubin G, Koeppl H. Optimal Kullback-Leibler aggregation
via information bottleneck. IEEE Transactions on Automatic Control. 2015;60(4):1010-1022.
doi:10.1109/TAC.2014.2364971
apa: Geiger, B., Petrov, T., Kubin, G., & Koeppl, H. (2015). Optimal Kullback-Leibler
aggregation via information bottleneck. IEEE Transactions on Automatic Control.
IEEE. https://doi.org/10.1109/TAC.2014.2364971
chicago: Geiger, Bernhard, Tatjana Petrov, Gernot Kubin, and Heinz Koeppl. “Optimal
Kullback-Leibler Aggregation via Information Bottleneck.” IEEE Transactions
on Automatic Control. IEEE, 2015. https://doi.org/10.1109/TAC.2014.2364971.
ieee: B. Geiger, T. Petrov, G. Kubin, and H. Koeppl, “Optimal Kullback-Leibler aggregation
via information bottleneck,” IEEE Transactions on Automatic Control, vol.
60, no. 4. IEEE, pp. 1010–1022, 2015.
ista: Geiger B, Petrov T, Kubin G, Koeppl H. 2015. Optimal Kullback-Leibler aggregation
via information bottleneck. IEEE Transactions on Automatic Control. 60(4), 1010–1022.
mla: Geiger, Bernhard, et al. “Optimal Kullback-Leibler Aggregation via Information
Bottleneck.” IEEE Transactions on Automatic Control, vol. 60, no. 4, IEEE,
2015, pp. 1010–22, doi:10.1109/TAC.2014.2364971.
short: B. Geiger, T. Petrov, G. Kubin, H. Koeppl, IEEE Transactions on Automatic
Control 60 (2015) 1010–1022.
date_created: 2018-12-11T11:54:18Z
date_published: 2015-04-01T00:00:00Z
date_updated: 2025-09-23T09:45:33Z
day: '01'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1109/TAC.2014.2364971
external_id:
arxiv:
- '1304.6603'
isi:
- '000351731600009'
fulldoi: https://doi.org/10.1109/TAC.2014.2364971
intvolume: ' 60'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1304.6603
month: '04'
oa: 1
oa_version: Preprint
page: 1010 - 1022
publication: IEEE Transactions on Automatic Control
publication_identifier:
issn:
- 0018-9286
publication_status: published
publisher: IEEE
publist_id: '5262'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Optimal Kullback-Leibler aggregation via information bottleneck
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 60
year: '2015'
...
---
_id: '1542'
abstract:
- lang: eng
text: 'The theory of population genetics and evolutionary computation have been
evolving separately for nearly 30 years. Many results have been independently
obtained in both fields and many others are unique to its respective field. We
aim to bridge this gap by developing a unifying framework for evolutionary processes
that allows both evolutionary algorithms and population genetics models to be
cast in the same formal framework. The framework we present here decomposes the
evolutionary process into its several components in order to facilitate the identification
of similarities between different models. In particular, we propose a classification
of evolutionary operators based on the defining properties of the different components.
We cast several commonly used operators from both fields into this common framework.
Using this, we map different evolutionary and genetic algorithms to different
evolutionary regimes and identify candidates with the most potential for the translation
of results between the fields. This provides a unified description of evolutionary
processes and represents a stepping stone towards new tools and results to both
fields. '
article_processing_charge: No
author:
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Golnaz
full_name: Badkobeh, Golnaz
last_name: Badkobeh
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Doğan
full_name: Çörüş, Doğan
last_name: Çörüş
- first_name: Duccuong
full_name: Dang, Duccuong
last_name: Dang
- first_name: Tobias
full_name: Friedrich, Tobias
last_name: Friedrich
- first_name: Per
full_name: Lehre, Per
last_name: Lehre
- first_name: Dirk
full_name: Sudholt, Dirk
last_name: Sudholt
- first_name: Andrew
full_name: Sutton, Andrew
last_name: Sutton
- first_name: Barbora
full_name: Trubenova, Barbora
id: 42302D54-F248-11E8-B48F-1D18A9856A87
last_name: Trubenova
orcid: 0000-0002-6873-2967
citation:
ama: Paixao T, Badkobeh G, Barton NH, et al. Toward a unifying framework for evolutionary
processes. Journal of Theoretical Biology. 2015;383:28-43. doi:10.1016/j.jtbi.2015.07.011
apa: Paixao, T., Badkobeh, G., Barton, N. H., Çörüş, D., Dang, D., Friedrich, T.,
… Trubenova, B. (2015). Toward a unifying framework for evolutionary processes.
Journal of Theoretical Biology. Elsevier. https://doi.org/10.1016/j.jtbi.2015.07.011
chicago: Paixao, Tiago, Golnaz Badkobeh, Nicholas H Barton, Doğan Çörüş, Duccuong
Dang, Tobias Friedrich, Per Lehre, Dirk Sudholt, Andrew Sutton, and Barbora Trubenova.
“Toward a Unifying Framework for Evolutionary Processes.” Journal of Theoretical
Biology. Elsevier, 2015. https://doi.org/10.1016/j.jtbi.2015.07.011.
ieee: T. Paixao et al., “Toward a unifying framework for evolutionary processes,”
Journal of Theoretical Biology, vol. 383. Elsevier, pp. 28–43, 2015.
ista: Paixao T, Badkobeh G, Barton NH, Çörüş D, Dang D, Friedrich T, Lehre P, Sudholt
D, Sutton A, Trubenova B. 2015. Toward a unifying framework for evolutionary processes.
Journal of Theoretical Biology. 383, 28–43.
mla: Paixao, Tiago, et al. “Toward a Unifying Framework for Evolutionary Processes.”
Journal of Theoretical Biology, vol. 383, Elsevier, 2015, pp. 28–43, doi:10.1016/j.jtbi.2015.07.011.
short: T. Paixao, G. Badkobeh, N.H. Barton, D. Çörüş, D. Dang, T. Friedrich, P.
Lehre, D. Sudholt, A. Sutton, B. Trubenova, Journal of Theoretical Biology 383
(2015) 28–43.
corr_author: '1'
das_tickbox: '1'
date_created: 2018-12-11T11:52:37Z
date_published: 2015-10-21T00:00:00Z
date_updated: 2026-07-07T13:12:13Z
day: '21'
ddc:
- '570'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1016/j.jtbi.2015.07.011
ec_funded: 1
external_id:
isi:
- '000362056300005'
file:
- access_level: open_access
checksum: 33b60ecfea60764756a9ee9df5eb65ca
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:53Z
date_updated: 2020-07-14T12:45:01Z
file_id: '5244'
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file_size: 595307
relation: main_file
file_date_updated: 2020-07-14T12:45:01Z
fulldoi: https://doi.org/10.1016/j.jtbi.2015.07.011
has_accepted_license: '1'
intvolume: ' 383'
isi: 1
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/4.0/
month: '10'
oa: 1
oa_version: Published Version
page: 28 - 43
project:
- _id: 25B1EC9E-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '618091'
name: Speed of Adaptation in Population Genetics and Evolutionary Computation
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
publication: Journal of Theoretical Biology
publication_status: published
publisher: Elsevier
publist_id: '5629'
pubrep_id: '483'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Toward a unifying framework for evolutionary processes
tmp:
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legal_code_url: https://creativecommons.org/licenses/by-nc-nd/4.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
(CC BY-NC-ND 4.0)
short: CC BY-NC-ND (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 383
year: '2015'
...
---
_id: '1666'
abstract:
- lang: eng
text: Evolution of gene regulation is crucial for our understanding of the phenotypic
differences between species, populations and individuals. Sequence-specific binding
of transcription factors to the regulatory regions on the DNA is a key regulatory
mechanism that determines gene expression and hence heritable phenotypic variation.
We use a biophysical model for directional selection on gene expression to estimate
the rates of gain and loss of transcription factor binding sites (TFBS) in finite
populations under both point and insertion/deletion mutations. Our results show
that these rates are typically slow for a single TFBS in an isolated DNA region,
unless the selection is extremely strong. These rates decrease drastically with
increasing TFBS length or increasingly specific protein-DNA interactions, making
the evolution of sites longer than ∼ 10 bp unlikely on typical eukaryotic speciation
timescales. Similarly, evolution converges to the stationary distribution of binding
sequences very slowly, making the equilibrium assumption questionable. The availability
of longer regulatory sequences in which multiple binding sites can evolve simultaneously,
the presence of “pre-sites” or partially decayed old sites in the initial sequence,
and biophysical cooperativity between transcription factors, can all facilitate
gain of TFBS and reconcile theoretical calculations with timescales inferred from
comparative genomics.
article_processing_charge: No
author:
- first_name: Murat
full_name: Tugrul, Murat
id: 37C323C6-F248-11E8-B48F-1D18A9856A87
last_name: Tugrul
orcid: 0000-0002-8523-0758
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
citation:
ama: Tugrul M, Paixao T, Barton NH, Tkačik G. Dynamics of transcription factor binding
site evolution. PLoS Genetics. 2015;11(11). doi:10.1371/journal.pgen.1005639
apa: Tugrul, M., Paixao, T., Barton, N. H., & Tkačik, G. (2015). Dynamics of
transcription factor binding site evolution. PLoS Genetics. Public Library
of Science. https://doi.org/10.1371/journal.pgen.1005639
chicago: Tugrul, Murat, Tiago Paixao, Nicholas H Barton, and Gašper Tkačik. “Dynamics
of Transcription Factor Binding Site Evolution.” PLoS Genetics. Public
Library of Science, 2015. https://doi.org/10.1371/journal.pgen.1005639.
ieee: M. Tugrul, T. Paixao, N. H. Barton, and G. Tkačik, “Dynamics of transcription
factor binding site evolution,” PLoS Genetics, vol. 11, no. 11. Public
Library of Science, 2015.
ista: Tugrul M, Paixao T, Barton NH, Tkačik G. 2015. Dynamics of transcription factor
binding site evolution. PLoS Genetics. 11(11).
mla: Tugrul, Murat, et al. “Dynamics of Transcription Factor Binding Site Evolution.”
PLoS Genetics, vol. 11, no. 11, Public Library of Science, 2015, doi:10.1371/journal.pgen.1005639.
short: M. Tugrul, T. Paixao, N.H. Barton, G. Tkačik, PLoS Genetics 11 (2015).
date_created: 2018-12-11T11:53:21Z
date_published: 2015-11-06T00:00:00Z
date_updated: 2026-07-29T11:31:13Z
day: '06'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pgen.1005639
ec_funded: 1
external_id:
isi:
- '000366179000022'
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checksum: a4e72fca5ccf40ddacf4d08c8e46b554
content_type: application/pdf
creator: system
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file_name: IST-2016-463-v1+1_journal.pgen.1005639.pdf
file_size: 2580778
relation: main_file
file_date_updated: 2020-07-14T12:45:10Z
fulldoi: https://doi.org/10.1371/journal.pgen.1005639
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
issue: '11'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
project:
- _id: 25B07788-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '250152'
name: Limits to selection in biology and in evolutionary computation
publication: PLoS Genetics
publication_status: published
publisher: Public Library of Science
publist_id: '5483'
pubrep_id: '463'
quality_controlled: '1'
related_material:
record:
- id: '9712'
relation: research_data
status: public
- id: '1131'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: Dynamics of transcription factor binding site evolution
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 11
year: '2015'
...
---
_id: '2083'
abstract:
- lang: eng
text: Understanding the effects of sex and migration on adaptation to novel environments
remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas
reinhardtii, we investigated how sex and migration affected rates of evolutionary
rescue in a sink environment, and subsequent changes in fitness following evolutionary
rescue. We show that sex and migration affect both the rate of evolutionary rescue
and subsequent adaptation. However, their combined effects change as the populations
adapt to a sink habitat. Both sex and migration independently increased rates
of evolutionary rescue, but the effect of sex on subsequent fitness improvements,
following initial rescue, changed with migration, as sex was beneficial in the
absence of migration but constraining adaptation when combined with migration.
These results suggest that sex and migration are beneficial during the initial
stages of adaptation, but can become detrimental as the population adapts to its
environment.
acknowledgement: The authors are grateful to the Leverhulme Trust (F/00 215/AW) for
funding this work.
article_processing_charge: No
article_type: original
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Andrew
full_name: Morgan, Andrew
last_name: Morgan
- first_name: Paul
full_name: Neve, Paul
last_name: Neve
- first_name: Nick
full_name: Colegrave, Nick
last_name: Colegrave
citation:
ama: Lagator M, Morgan A, Neve P, Colegrave N. Role of sex and migration in adaptation
to sink environments. Evolution. 2014;68(8):2296-2305. doi:10.1111/evo.12440
apa: Lagator, M., Morgan, A., Neve, P., & Colegrave, N. (2014). Role of sex
and migration in adaptation to sink environments. Evolution. Wiley. https://doi.org/10.1111/evo.12440
chicago: Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Role of Sex
and Migration in Adaptation to Sink Environments.” Evolution. Wiley, 2014.
https://doi.org/10.1111/evo.12440.
ieee: M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Role of sex and migration
in adaptation to sink environments,” Evolution, vol. 68, no. 8. Wiley,
pp. 2296–2305, 2014.
ista: Lagator M, Morgan A, Neve P, Colegrave N. 2014. Role of sex and migration
in adaptation to sink environments. Evolution. 68(8), 2296–2305.
mla: Lagator, Mato, et al. “Role of Sex and Migration in Adaptation to Sink Environments.”
Evolution, vol. 68, no. 8, Wiley, 2014, pp. 2296–305, doi:10.1111/evo.12440.
short: M. Lagator, A. Morgan, P. Neve, N. Colegrave, Evolution 68 (2014) 2296–2305.
corr_author: '1'
date_created: 2018-12-11T11:55:36Z
date_published: 2014-04-25T00:00:00Z
date_updated: 2025-09-29T11:46:47Z
day: '25'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1111/evo.12440
external_id:
isi:
- '000340470600012'
file:
- access_level: open_access
checksum: 8d459b07e4a11bb5fde92d969184fe48
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file_size: 467254
relation: main_file
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intvolume: ' 68'
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issue: '8'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
page: 2296 - 2305
publication: Evolution
publication_status: published
publisher: Wiley
publist_id: '4954'
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related_material:
record:
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relation: research_data
status: public
scopus_import: '1'
status: public
title: Role of sex and migration in adaptation to sink environments
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 68
year: '2014'
...
---
_id: '1894'
abstract:
- lang: eng
text: 'Background: Bacterial Dsb enzymes are involved in the oxidative folding of
many proteins, through the formation of disulfide bonds between their cysteine
residues. The Dsb protein network has been well characterized in cells of the
model microorganism Escherichia coli. To gain insight into the functioning of
the Dsb system in epsilon-Proteobacteria, where it plays an important role in
the colonization process, we studied two homologs of the main Escherichia coli
Dsb oxidase (EcDsbA) that are present in the cells of the enteric pathogen Campylobacter
jejuni, the most frequently reported bacterial cause of human enteritis in the
world. Methods and Results: Phylogenetic analysis suggests the horizontal transfer
of the epsilon-Proteobacterial DsbAs from a common ancestor to gamma-Proteobacteria,
which then gave rise to the DsbL lineage. Phenotype and enzymatic assays suggest
that the two C. jejuni DsbAs play different roles in bacterial cells and have
divergent substrate spectra. CjDsbA1 is essential for the motility and autoagglutination
phenotypes, while CjDsbA2 has no impact on those processes. CjDsbA1 plays a critical
role in the oxidative folding that ensures the activity of alkaline phosphatase
CjPhoX, whereas CjDsbA2 is crucial for the activity of arylsulfotransferase CjAstA,
encoded within the dsbA2-dsbB-astA operon. Conclusions: Our results show that
CjDsbA1 is the primary thiol-oxidoreductase affecting life processes associated
with bacterial spread and host colonization, as well as ensuring the oxidative
folding of particular protein substrates. In contrast, CjDsbA2 activity does not
affect the same processes and so far its oxidative folding activity has been demonstrated
for one substrate, arylsulfotransferase CjAstA. The results suggest the cooperation
between CjDsbA2 and CjDsbB. In the case of the CjDsbA1, this cooperation is not
exclusive and there is probably another protein to be identified in C. jejuni
cells that acts to re-oxidize CjDsbA1. Altogether the data presented here constitute
the considerable insight to the Epsilonproteobacterial Dsb systems, which have
been poorly understood so far.'
article_number: e106247
article_processing_charge: No
author:
- first_name: Anna
full_name: Grabowska, Anna
last_name: Grabowska
- first_name: Ewa
full_name: Wywiał, Ewa
last_name: Wywiał
- first_name: Stanislaw
full_name: Dunin Horkawicz, Stanislaw
last_name: Dunin Horkawicz
- first_name: Anna
full_name: Łasica, Anna
last_name: Łasica
- first_name: Marc
full_name: Wösten, Marc
last_name: Wösten
- first_name: Anna A
full_name: Nagy-Staron, Anna A
id: 3ABC5BA6-F248-11E8-B48F-1D18A9856A87
last_name: Nagy-Staron
orcid: 0000-0002-1391-8377
- first_name: Renata
full_name: Godlewska, Renata
last_name: Godlewska
- first_name: Katarzyna
full_name: Bocian Ostrzycka, Katarzyna
last_name: Bocian Ostrzycka
- first_name: Katarzyna
full_name: Pieńkowska, Katarzyna
last_name: Pieńkowska
- first_name: Paweł
full_name: Łaniewski, Paweł
last_name: Łaniewski
- first_name: Janusz
full_name: Bujnicki, Janusz
last_name: Bujnicki
- first_name: Jos
full_name: Van Putten, Jos
last_name: Van Putten
- first_name: Elzbieta
full_name: Jagusztyn Krynicka, Elzbieta
last_name: Jagusztyn Krynicka
citation:
ama: Grabowska A, Wywiał E, Dunin Horkawicz S, et al. Functional and bioinformatics
analysis of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase,
DsbA. PLoS One. 2014;9(9). doi:10.1371/journal.pone.0106247
apa: Grabowska, A., Wywiał, E., Dunin Horkawicz, S., Łasica, A., Wösten, M., Nagy-Staron,
A. A., … Jagusztyn Krynicka, E. (2014). Functional and bioinformatics analysis
of two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA.
PLoS One. Public Library of Science. https://doi.org/10.1371/journal.pone.0106247
chicago: Grabowska, Anna, Ewa Wywiał, Stanislaw Dunin Horkawicz, Anna Łasica, Marc
Wösten, Anna A Nagy-Staron, Renata Godlewska, et al. “Functional and Bioinformatics
Analysis of Two Campylobacter Jejuni Homologs of the Thiol-Disulfide Oxidoreductase,
DsbA.” PLoS One. Public Library of Science, 2014. https://doi.org/10.1371/journal.pone.0106247.
ieee: A. Grabowska et al., “Functional and bioinformatics analysis of two
Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA,” PLoS
One, vol. 9, no. 9. Public Library of Science, 2014.
ista: Grabowska A, Wywiał E, Dunin Horkawicz S, Łasica A, Wösten M, Nagy-Staron
AA, Godlewska R, Bocian Ostrzycka K, Pieńkowska K, Łaniewski P, Bujnicki J, Van
Putten J, Jagusztyn Krynicka E. 2014. Functional and bioinformatics analysis of
two Campylobacter jejuni homologs of the thiol-disulfide oxidoreductase, DsbA.
PLoS One. 9(9), e106247.
mla: Grabowska, Anna, et al. “Functional and Bioinformatics Analysis of Two Campylobacter
Jejuni Homologs of the Thiol-Disulfide Oxidoreductase, DsbA.” PLoS One,
vol. 9, no. 9, e106247, Public Library of Science, 2014, doi:10.1371/journal.pone.0106247.
short: A. Grabowska, E. Wywiał, S. Dunin Horkawicz, A. Łasica, M. Wösten, A.A. Nagy-Staron,
R. Godlewska, K. Bocian Ostrzycka, K. Pieńkowska, P. Łaniewski, J. Bujnicki, J.
Van Putten, E. Jagusztyn Krynicka, PLoS One 9 (2014).
date_created: 2018-12-11T11:54:35Z
date_published: 2014-09-02T00:00:00Z
date_updated: 2025-09-29T13:05:10Z
day: '02'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1371/journal.pone.0106247
external_id:
isi:
- '000341231500064'
file:
- access_level: open_access
checksum: 7d02c3da7f72b82bb5d7932d80c3251f
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:19Z
date_updated: 2020-07-14T12:45:20Z
file_id: '5205'
file_name: IST-2016-438-v1+1_journal.pone.0106247.pdf
file_size: 4248801
relation: main_file
file_date_updated: 2020-07-14T12:45:20Z
fulldoi: https://doi.org/10.1371/journal.pone.0106247
has_accepted_license: '1'
intvolume: ' 9'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
publication: PLoS One
publication_status: published
publisher: Public Library of Science
publist_id: '5201'
pubrep_id: '438'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Functional and bioinformatics analysis of two Campylobacter jejuni homologs
of the thiol-disulfide oxidoreductase, DsbA
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 9
year: '2014'
...
---
_id: '1913'
abstract:
- lang: eng
text: 'Deposits of phosphorylated tau protein and convergence of pathology in the
hippocampus are the hallmarks of neurodegenerative tauopathies. Thus we aimed
to evaluate whether regional and cellular vulnerability patterns in the hippocampus
distinguish tauopathies or are influenced by their concomitant presence. Methods:
We created a heat map of phospho-tau (AT8) immunoreactivity patterns in 24 hippocampal
subregions/layers in individuals with Alzheimer''s disease (AD)-related neurofibrillary
degeneration (n = 40), Pick''s disease (n = 8), progressive supranuclear palsy
(n = 7), corticobasal degeneration (n = 6), argyrophilic grain disease (AGD, n
= 18), globular glial tauopathy (n = 5), and tau-astrogliopathy of the elderly
(n = 10). AT8 immunoreactivity patterns were compared by mathematical analysis.
Results: Our study reveals disease-specific hot spots and regional selective vulnerability
for these disorders. The pattern of hippocampal AD-related tau pathology is strongly
influenced by concomitant AGD. Mathematical analysis reveals that hippocampal
involvement in primary tauopathies is distinguishable from early-stage AD-related
neurofibrillary degeneration. Conclusion: Our data demonstrate disease-specific
AT8 immunoreactivity patterns and hot spots in the hippocampus even in tauopathies,
which primarily do not affect the hippocampus. These hot spots can be shifted
to other regions by the co-occurrence of tauopathies like AGD. Our observations
support the notion that globular glial tauopathies and tau-astrogliopathy of the
elderly are distinct entities.'
acknowledgement: This study was supported by the European Commission’s 7th Framework
Programme under GA No. 278486, ‘DEVELAGE’.
article_processing_charge: No
article_type: original
author:
- first_name: Ivan
full_name: Milenković, Ivan
last_name: Milenković
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
- first_name: Gábor
full_name: Kovács, Gábor
last_name: Kovács
citation:
ama: Milenković I, Petrov T, Kovács G. Patterns of hippocampal tau pathology differentiate
neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders.
2014;38(5-6):375-388. doi:10.1159/000365548
apa: Milenković, I., Petrov, T., & Kovács, G. (2014). Patterns of hippocampal
tau pathology differentiate neurodegenerative dementias. Dementia and Geriatric
Cognitive Disorders. Karger Publishers. https://doi.org/10.1159/000365548
chicago: Milenković, Ivan, Tatjana Petrov, and Gábor Kovács. “Patterns of Hippocampal
Tau Pathology Differentiate Neurodegenerative Dementias.” Dementia and Geriatric
Cognitive Disorders. Karger Publishers, 2014. https://doi.org/10.1159/000365548.
ieee: I. Milenković, T. Petrov, and G. Kovács, “Patterns of hippocampal tau pathology
differentiate neurodegenerative dementias,” Dementia and Geriatric Cognitive
Disorders, vol. 38, no. 5–6. Karger Publishers, pp. 375–388, 2014.
ista: Milenković I, Petrov T, Kovács G. 2014. Patterns of hippocampal tau pathology
differentiate neurodegenerative dementias. Dementia and Geriatric Cognitive Disorders.
38(5–6), 375–388.
mla: Milenković, Ivan, et al. “Patterns of Hippocampal Tau Pathology Differentiate
Neurodegenerative Dementias.” Dementia and Geriatric Cognitive Disorders,
vol. 38, no. 5–6, Karger Publishers, 2014, pp. 375–88, doi:10.1159/000365548.
short: I. Milenković, T. Petrov, G. Kovács, Dementia and Geriatric Cognitive Disorders
38 (2014) 375–388.
date_created: 2018-12-11T11:54:41Z
date_published: 2014-11-07T00:00:00Z
date_updated: 2026-06-18T18:13:04Z
day: '07'
ddc:
- '570'
department:
- _id: CaGu
doi: 10.1159/000365548
external_id:
isi:
- '000344049900011'
pmid:
- '25195847'
fulldoi: https://doi.org/10.1159/000365548
intvolume: ' 38'
isi: 1
issue: 5-6
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://kops.uni-konstanz.de/bitstream/123456789/42127/1/Milenkovic_2-17ivylo2up0798.pdf
month: '11'
oa: 1
oa_version: Published Version
page: 375 - 388
pmid: 1
publication: Dementia and Geriatric Cognitive Disorders
publication_identifier:
issn:
- 1420-8008
publication_status: published
publisher: Karger Publishers
publist_id: '5181'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Patterns of hippocampal tau pathology differentiate neurodegenerative dementias
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 38
year: '2014'
...
---
_id: '2056'
abstract:
- lang: eng
text: 'We consider a continuous-time Markov chain (CTMC) whose state space is partitioned
into aggregates, and each aggregate is assigned a probability measure. A sufficient
condition for defining a CTMC over the aggregates is presented as a variant of
weak lumpability, which also characterizes that the measure over the original
process can be recovered from that of the aggregated one. We show how the applicability
of de-aggregation depends on the initial distribution. The application section
is devoted to illustrate how the developed theory aids in reducing CTMC models
of biochemical systems particularly in connection to protein-protein interactions.
We assume that the model is written by a biologist in form of site-graph-rewrite
rules. Site-graph-rewrite rules compactly express that, often, only a local context
of a protein (instead of a full molecular species) needs to be in a certain configuration
in order to trigger a reaction event. This observation leads to suitable aggregate
Markov chains with smaller state spaces, thereby providing sufficient reduction
in computational complexity. This is further exemplified in two case studies:
simple unbounded polymerization and early EGFR/insulin crosstalk.'
acknowledgement: T. Petrov is supported by SystemsX.ch—the Swiss Inititative for Systems
Biology.
article_processing_charge: No
arxiv: 1
author:
- first_name: Arnab
full_name: Ganguly, Arnab
last_name: Ganguly
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
- first_name: Heinz
full_name: Koeppl, Heinz
last_name: Koeppl
citation:
ama: Ganguly A, Petrov T, Koeppl H. Markov chain aggregation and its applications
to combinatorial reaction networks. Journal of Mathematical Biology. 2014;69(3):767-797.
doi:10.1007/s00285-013-0738-7
apa: Ganguly, A., Petrov, T., & Koeppl, H. (2014). Markov chain aggregation
and its applications to combinatorial reaction networks. Journal of Mathematical
Biology. Springer. https://doi.org/10.1007/s00285-013-0738-7
chicago: Ganguly, Arnab, Tatjana Petrov, and Heinz Koeppl. “Markov Chain Aggregation
and Its Applications to Combinatorial Reaction Networks.” Journal of Mathematical
Biology. Springer, 2014. https://doi.org/10.1007/s00285-013-0738-7.
ieee: A. Ganguly, T. Petrov, and H. Koeppl, “Markov chain aggregation and its applications
to combinatorial reaction networks,” Journal of Mathematical Biology, vol.
69, no. 3. Springer, pp. 767–797, 2014.
ista: Ganguly A, Petrov T, Koeppl H. 2014. Markov chain aggregation and its applications
to combinatorial reaction networks. Journal of Mathematical Biology. 69(3), 767–797.
mla: Ganguly, Arnab, et al. “Markov Chain Aggregation and Its Applications to Combinatorial
Reaction Networks.” Journal of Mathematical Biology, vol. 69, no. 3, Springer,
2014, pp. 767–97, doi:10.1007/s00285-013-0738-7.
short: A. Ganguly, T. Petrov, H. Koeppl, Journal of Mathematical Biology 69 (2014)
767–797.
date_created: 2018-12-11T11:55:28Z
date_published: 2014-11-20T00:00:00Z
date_updated: 2025-09-29T11:50:22Z
day: '20'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1007/s00285-013-0738-7
external_id:
arxiv:
- '1303.4532'
isi:
- '000340588700008'
fulldoi: https://doi.org/10.1007/s00285-013-0738-7
intvolume: ' 69'
isi: 1
issue: '3'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: http://arxiv.org/abs/1303.4532
month: '11'
oa: 1
oa_version: Submitted Version
page: 767 - 797
publication: Journal of Mathematical Biology
publication_status: published
publisher: Springer
publist_id: '4990'
quality_controlled: '1'
scopus_import: '1'
status: public
title: Markov chain aggregation and its applications to combinatorial reaction networks
type: journal_article
user_id: 317138e5-6ab7-11ef-aa6d-ffef3953e345
volume: 69
year: '2014'
...
---
_id: '9747'
abstract:
- lang: eng
text: Understanding the effects of sex and migration on adaptation to novel environments
remains a key problem in evolutionary biology. Using a single-cell alga Chlamydomonas
reinhardtii, we investigated how sex and migration affected rates of evolutionary
rescue in a sink environment, and subsequent changes in fitness following evolutionary
rescue. We show that sex and migration affect both the rate of evolutionary rescue
and subsequent adaptation. However, their combined effects change as the populations
adapt to a sink habitat. Both sex and migration independently increased rates
of evolutionary rescue, but the effect of sex on subsequent fitness improvements,
following initial rescue, changed with migration, as sex was beneficial in the
absence of migration but constraining adaptation when combined with migration.
These results suggest that sex and migration are beneficial during the initial
stages of adaptation, but can become detrimental as the population adapts to its
environment.
article_processing_charge: No
author:
- first_name: Mato
full_name: Lagator, Mato
id: 345D25EC-F248-11E8-B48F-1D18A9856A87
last_name: Lagator
- first_name: Andrew
full_name: Morgan, Andrew
last_name: Morgan
- first_name: Paul
full_name: Neve, Paul
last_name: Neve
- first_name: Nick
full_name: Colegrave, Nick
last_name: Colegrave
citation:
ama: 'Lagator M, Morgan A, Neve P, Colegrave N. Data from: Role of sex and migration
in adaptation to sink environments. 2014. doi:10.5061/dryad.s42n1'
apa: 'Lagator, M., Morgan, A., Neve, P., & Colegrave, N. (2014). Data from:
Role of sex and migration in adaptation to sink environments. Dryad. https://doi.org/10.5061/dryad.s42n1'
chicago: 'Lagator, Mato, Andrew Morgan, Paul Neve, and Nick Colegrave. “Data from:
Role of Sex and Migration in Adaptation to Sink Environments.” Dryad, 2014. https://doi.org/10.5061/dryad.s42n1.'
ieee: 'M. Lagator, A. Morgan, P. Neve, and N. Colegrave, “Data from: Role of sex
and migration in adaptation to sink environments.” Dryad, 2014.'
ista: 'Lagator M, Morgan A, Neve P, Colegrave N. 2014. Data from: Role of sex and
migration in adaptation to sink environments, Dryad, 10.5061/dryad.s42n1.'
mla: 'Lagator, Mato, et al. Data from: Role of Sex and Migration in Adaptation
to Sink Environments. Dryad, 2014, doi:10.5061/dryad.s42n1.'
short: M. Lagator, A. Morgan, P. Neve, N. Colegrave, (2014).
date_created: 2021-07-28T15:32:55Z
date_published: 2014-04-17T00:00:00Z
date_updated: 2025-09-29T11:46:47Z
day: '17'
department:
- _id: CaGu
doi: 10.5061/dryad.s42n1
fulldoi: https://doi.org/10.5061/dryad.s42n1
main_file_link:
- open_access: '1'
url: https://doi.org/10.5061/dryad.s42n1
month: '04'
oa: 1
oa_version: Published Version
publisher: Dryad
related_material:
record:
- id: '2083'
relation: used_in_publication
status: public
status: public
title: 'Data from: Role of sex and migration in adaptation to sink environments'
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2014'
...