---
_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
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
date_created: 2018-12-11T11:52:31Z
date_published: 2016-01-10T00:00:00Z
date_updated: 2021-01-12T06:51:22Z
day: '10'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1007/978-3-319-26916-0_10
ec_funded: 1
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 9271
year: '2016'
...
---
_id: '1320'
abstract:
- lang: eng
text: 'In recent years, several biomolecular systems have been shown to be scale-invariant
(SI), i.e. to show the same output dynamics when exposed to geometrically scaled
input signals (u → pu, p > 0) after pre-adaptation to accordingly scaled constant
inputs. In this article, we show that SI systems-as well as systems invariant
with respect to other input transformations-can realize nonlinear differential
operators: when excited by inputs obeying functional forms characteristic for
a given class of invariant systems, the systems'' outputs converge to constant
values directly quantifying the speed of the input.'
acknowledgement: The research leading to these results has received funding from the
People Programme (Marie Curie Actions) of the European Union's Seventh Framework
Programme (FP7/2007-2013) under REA grant agreement n° [291734]. Work supported
in part by grants AFOSR FA9550-14-1-0060 and NIH 1R01GM100473.
article_number: '7526722'
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Eduardo
full_name: Sontag, Eduardo
last_name: Sontag
citation:
ama: 'Lang M, Sontag E. Scale-invariant systems realize nonlinear differential operators.
In: Vol 2016-July. IEEE; 2016. doi:10.1109/ACC.2016.7526722'
apa: 'Lang, M., & Sontag, E. (2016). Scale-invariant systems realize nonlinear
differential operators (Vol. 2016–July). Presented at the ACC: American Control
Conference, Boston, MA, USA: IEEE. https://doi.org/10.1109/ACC.2016.7526722'
chicago: Lang, Moritz, and Eduardo Sontag. “Scale-Invariant Systems Realize Nonlinear
Differential Operators,” Vol. 2016–July. IEEE, 2016. https://doi.org/10.1109/ACC.2016.7526722.
ieee: 'M. Lang and E. Sontag, “Scale-invariant systems realize nonlinear differential
operators,” presented at the ACC: American Control Conference, Boston, MA, USA,
2016, vol. 2016–July.'
ista: 'Lang M, Sontag E. 2016. Scale-invariant systems realize nonlinear differential
operators. ACC: American Control Conference vol. 2016–July, 7526722.'
mla: Lang, Moritz, and Eduardo Sontag. Scale-Invariant Systems Realize Nonlinear
Differential Operators. Vol. 2016–July, 7526722, IEEE, 2016, doi:10.1109/ACC.2016.7526722.
short: M. Lang, E. Sontag, in:, IEEE, 2016.
conference:
end_date: 2016-07-08
location: Boston, MA, USA
name: 'ACC: American Control Conference'
start_date: 2016-07-06
date_created: 2018-12-11T11:51:21Z
date_published: 2016-07-28T00:00:00Z
date_updated: 2021-01-12T06:49:51Z
day: '28'
ddc:
- '003'
- '621'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1109/ACC.2016.7526722
ec_funded: 1
file:
- access_level: local
checksum: 7219432b43defc62a0d45f48d4ce6a19
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:17Z
date_updated: 2020-07-14T12:44:43Z
file_id: '5203'
file_name: IST-2017-810-v1+1_root.pdf
file_size: 539166
relation: main_file
file_date_updated: 2020-07-14T12:44:43Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa_version: Preprint
project:
- _id: 25681D80-B435-11E9-9278-68D0E5697425
call_identifier: FP7
grant_number: '291734'
name: International IST Postdoc Fellowship Programme
publication_status: published
publisher: IEEE
publist_id: '5950'
pubrep_id: '810'
quality_controlled: '1'
scopus_import: 1
status: public
title: Scale-invariant systems realize nonlinear differential operators
type: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 2016-July
year: '2016'
...
---
_id: '1332'
abstract:
- lang: eng
text: Antibiotic-sensitive and -resistant bacteria coexist in natural environments
with low, if detectable, antibiotic concentrations. Except possibly around localized
antibiotic sources, where resistance can provide a strong advantage, bacterial
fitness is dominated by stresses unaffected by resistance to the antibiotic. How
do such mixed and heterogeneous conditions influence the selective advantage or
disadvantage of antibiotic resistance? Here we find that sub-inhibitory levels
of tetracyclines potentiate selection for or against tetracycline resistance around
localized sources of almost any toxin or stress. Furthermore, certain stresses
generate alternating rings of selection for and against resistance around a localized
source of the antibiotic. In these conditions, localized antibiotic sources, even
at high strengths, can actually produce a net selection against resistance to
the antibiotic. Our results show that interactions between the effects of an antibiotic
and other stresses in inhomogeneous environments can generate pervasive, complex
patterns of selection both for and against antibiotic resistance.
acknowledgement: This work was partially supported by US National Institutes of Health
grant R01-GM081617, Israeli Centers of Research Excellence I-CORE Program ISF Grant
No. 152/11, and the European Research Council FP7 ERC Grant 281891.
article_number: '10333'
author:
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Adam
full_name: Palmer, Adam
last_name: Palmer
- first_name: Idan
full_name: Yelin, Idan
last_name: Yelin
- first_name: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Chait RP, Palmer A, Yelin I, Kishony R. Pervasive selection for and against
antibiotic resistance in inhomogeneous multistress environments. Nature Communications.
2016;7. doi:10.1038/ncomms10333
apa: Chait, R. P., Palmer, A., Yelin, I., & Kishony, R. (2016). Pervasive selection
for and against antibiotic resistance in inhomogeneous multistress environments.
Nature Communications. Nature Publishing Group. https://doi.org/10.1038/ncomms10333
chicago: Chait, Remy P, Adam Palmer, Idan Yelin, and Roy Kishony. “Pervasive Selection
for and against Antibiotic Resistance in Inhomogeneous Multistress Environments.”
Nature Communications. Nature Publishing Group, 2016. https://doi.org/10.1038/ncomms10333.
ieee: R. P. Chait, A. Palmer, I. Yelin, and R. Kishony, “Pervasive selection for
and against antibiotic resistance in inhomogeneous multistress environments,”
Nature Communications, vol. 7. Nature Publishing Group, 2016.
ista: Chait RP, Palmer A, Yelin I, Kishony R. 2016. Pervasive selection for and
against antibiotic resistance in inhomogeneous multistress environments. Nature
Communications. 7, 10333.
mla: Chait, Remy P., et al. “Pervasive Selection for and against Antibiotic Resistance
in Inhomogeneous Multistress Environments.” Nature Communications, vol.
7, 10333, Nature Publishing Group, 2016, doi:10.1038/ncomms10333.
short: R.P. Chait, A. Palmer, I. Yelin, R. Kishony, Nature Communications 7 (2016).
date_created: 2018-12-11T11:51:25Z
date_published: 2016-01-20T00:00:00Z
date_updated: 2021-01-12T06:49:57Z
day: '20'
ddc:
- '570'
- '579'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/ncomms10333
file:
- access_level: open_access
checksum: ef147bcbb8bd37e9079cf3ce06f5815d
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:13:52Z
date_updated: 2020-07-14T12:44:44Z
file_id: '5039'
file_name: IST-2016-662-v1+1_ncomms10333.pdf
file_size: 1844107
relation: main_file
file_date_updated: 2020-07-14T12:44:44Z
has_accepted_license: '1'
intvolume: ' 7'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
publication: Nature Communications
publication_status: published
publisher: Nature Publishing Group
publist_id: '5936'
pubrep_id: '662'
quality_controlled: '1'
scopus_import: 1
status: public
title: Pervasive selection for and against antibiotic resistance in inhomogeneous
multistress environments
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 7
year: '2016'
...
---
_id: '1342'
abstract:
- lang: eng
text: A key aspect of bacterial survival is the ability to evolve while migrating
across spatially varying environmental challenges. Laboratory experiments, however,
often study evolution in well-mixed systems. Here, we introduce an experimental
device, the microbial evolution and growth arena (MEGA)-plate, in which bacteria
spread and evolved on a large antibiotic landscape (120 × 60 centimeters) that
allowed visual observation of mutation and selection in a migrating bacterial
front.While resistance increased consistently, multiple coexisting lineages diversified
both phenotypically and genotypically. Analyzing mutants at and behind the propagating
front,we found that evolution is not always led by the most resistant mutants;
highly resistant mutants may be trapped behindmore sensitive lineages.TheMEGA-plate
provides a versatile platformfor studying microbial adaption and directly visualizing
evolutionary dynamics.
author:
- first_name: Michael
full_name: Baym, Michael
last_name: Baym
- first_name: Tami
full_name: Lieberman, Tami
last_name: Lieberman
- first_name: Eric
full_name: Kelsic, Eric
last_name: Kelsic
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Rotem
full_name: Gross, Rotem
last_name: Gross
- first_name: Idan
full_name: Yelin, Idan
last_name: Yelin
- first_name: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Baym M, Lieberman T, Kelsic E, et al. Spatiotemporal microbial evolution on
antibiotic landscapes. Science. 2016;353(6304):1147-1151. doi:10.1126/science.aag0822
apa: Baym, M., Lieberman, T., Kelsic, E., Chait, R. P., Gross, R., Yelin, I., &
Kishony, R. (2016). Spatiotemporal microbial evolution on antibiotic landscapes.
Science. American Association for the Advancement of Science. https://doi.org/10.1126/science.aag0822
chicago: Baym, Michael, Tami Lieberman, Eric Kelsic, Remy P Chait, Rotem Gross,
Idan Yelin, and Roy Kishony. “Spatiotemporal Microbial Evolution on Antibiotic
Landscapes.” Science. American Association for the Advancement of Science,
2016. https://doi.org/10.1126/science.aag0822.
ieee: M. Baym et al., “Spatiotemporal microbial evolution on antibiotic landscapes,”
Science, vol. 353, no. 6304. American Association for the Advancement of
Science, pp. 1147–1151, 2016.
ista: Baym M, Lieberman T, Kelsic E, Chait RP, Gross R, Yelin I, Kishony R. 2016.
Spatiotemporal microbial evolution on antibiotic landscapes. Science. 353(6304),
1147–1151.
mla: Baym, Michael, et al. “Spatiotemporal Microbial Evolution on Antibiotic Landscapes.”
Science, vol. 353, no. 6304, American Association for the Advancement of
Science, 2016, pp. 1147–51, doi:10.1126/science.aag0822.
short: M. Baym, T. Lieberman, E. Kelsic, R.P. Chait, R. Gross, I. Yelin, R. Kishony,
Science 353 (2016) 1147–1151.
date_created: 2018-12-11T11:51:29Z
date_published: 2016-09-09T00:00:00Z
date_updated: 2021-01-12T06:50:01Z
day: '09'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1126/science.aag0822
intvolume: ' 353'
issue: '6304'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5534434/
month: '09'
oa: 1
oa_version: Preprint
page: 1147 - 1151
publication: Science
publication_status: published
publisher: American Association for the Advancement of Science
publist_id: '5911'
quality_controlled: '1'
scopus_import: 1
status: public
title: Spatiotemporal microbial evolution on antibiotic landscapes
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 353
year: '2016'
...
---
_id: '1349'
abstract:
- lang: eng
text: Crossing fitness valleys is one of the major obstacles to function optimization.
In this paper we investigate how the structure of the fitness valley, namely its
depth d and length ℓ, influence the runtime of different strategies for crossing
these valleys. We present a runtime comparison between the (1+1) EA and two non-elitist
nature-inspired algorithms, Strong Selection Weak Mutation (SSWM) and the Metropolis
algorithm. While the (1+1) EA has to jump across the valley to a point of higher
fitness because it does not accept decreasing moves, the non-elitist algorithms
may cross the valley by accepting worsening moves. We show that while the runtime
of the (1+1) EA algorithm depends critically on the length of the valley, the
runtimes of the non-elitist algorithms depend crucially only on the depth of the
valley. In particular, the expected runtime of both SSWM and Metropolis is polynomial
in ℓ and exponential in d while the (1+1) EA is efficient only for valleys of
small length. Moreover, we show that both SSWM and Metropolis can also efficiently
optimize a rugged function consisting of consecutive valleys.
author:
- first_name: Pietro
full_name: Oliveto, Pietro
last_name: Oliveto
- first_name: Tiago
full_name: Paixao, Tiago
id: 2C5658E6-F248-11E8-B48F-1D18A9856A87
last_name: Paixao
orcid: 0000-0003-2361-3953
- first_name: Jorge
full_name: Heredia, Jorge
last_name: Heredia
- first_name: Dirk
full_name: Sudholt, Dirk
last_name: Sudholt
- first_name: Barbora
full_name: Trubenova, Barbora
id: 42302D54-F248-11E8-B48F-1D18A9856A87
last_name: Trubenova
orcid: 0000-0002-6873-2967
citation:
ama: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. When non-elitism outperforms
elitism for crossing fitness valleys. In: Proceedings of the Genetic and Evolutionary
Computation Conference 2016 . ACM; 2016:1163-1170. doi:10.1145/2908812.2908909'
apa: 'Oliveto, P., Paixao, T., Heredia, J., Sudholt, D., & Trubenova, B. (2016).
When non-elitism outperforms elitism for crossing fitness valleys. In Proceedings
of the Genetic and Evolutionary Computation Conference 2016 (pp. 1163–1170).
Denver, CO, USA: ACM. https://doi.org/10.1145/2908812.2908909'
chicago: Oliveto, Pietro, Tiago Paixao, Jorge Heredia, Dirk Sudholt, and Barbora
Trubenova. “When Non-Elitism Outperforms Elitism for Crossing Fitness Valleys.”
In Proceedings of the Genetic and Evolutionary Computation Conference 2016
, 1163–70. ACM, 2016. https://doi.org/10.1145/2908812.2908909.
ieee: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, and B. Trubenova, “When non-elitism
outperforms elitism for crossing fitness valleys,” in Proceedings of the Genetic
and Evolutionary Computation Conference 2016 , Denver, CO, USA, 2016, pp.
1163–1170.
ista: 'Oliveto P, Paixao T, Heredia J, Sudholt D, Trubenova B. 2016. When non-elitism
outperforms elitism for crossing fitness valleys. Proceedings of the Genetic and
Evolutionary Computation Conference 2016 . GECCO: Genetic and evolutionary computation
conference, 1163–1170.'
mla: Oliveto, Pietro, et al. “When Non-Elitism Outperforms Elitism for Crossing
Fitness Valleys.” Proceedings of the Genetic and Evolutionary Computation Conference
2016 , ACM, 2016, pp. 1163–70, doi:10.1145/2908812.2908909.
short: P. Oliveto, T. Paixao, J. Heredia, D. Sudholt, B. Trubenova, in:, Proceedings
of the Genetic and Evolutionary Computation Conference 2016 , ACM, 2016, pp. 1163–1170.
conference:
end_date: 2016-07-24
location: Denver, CO, USA
name: 'GECCO: Genetic and evolutionary computation conference'
start_date: 2016-07-20
date_created: 2018-12-11T11:51:31Z
date_published: 2016-07-20T00:00:00Z
date_updated: 2021-01-12T06:50:03Z
day: '20'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1145/2908812.2908909
ec_funded: 1
file:
- access_level: open_access
checksum: a1896e39e4113f2711e46b435d5f3e69
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:16:27Z
date_updated: 2020-07-14T12:44:45Z
file_id: '5214'
file_name: IST-2016-650-v1+1_p1163-oliveto.pdf
file_size: 979026
relation: main_file
file_date_updated: 2020-07-14T12:44:45Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: 1163 - 1170
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 Genetic and Evolutionary Computation Conference 2016 '
publication_status: published
publisher: ACM
publist_id: '5900'
pubrep_id: '650'
quality_controlled: '1'
scopus_import: 1
status: public
title: When non-elitism outperforms elitism for crossing fitness valleys
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: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
year: '2016'
...
---
_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'
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).
date_created: 2018-12-11T11:51:34Z
date_published: 2016-08-04T00:00:00Z
date_updated: 2023-09-07T12:53:49Z
day: '04'
ddc:
- '576'
department:
- _id: GaTk
- _id: NiBa
- _id: CaGu
doi: 10.1038/ncomms12307
ec_funded: 1
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
has_accepted_license: '1'
intvolume: ' 7'
language:
- iso: eng
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
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.
date_created: 2018-12-11T11:51:34Z
date_published: 2016-04-19T00:00:00Z
date_updated: 2021-01-12T06:50:08Z
day: '19'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1073/pnas.1518830113
ec_funded: 1
external_id:
pmid:
- '27044080'
intvolume: ' 113'
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.
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.
date_created: 2018-12-11T11:51:57Z
date_published: 2016-03-01T00:00:00Z
date_updated: 2021-01-12T06:50:39Z
day: '01'
ddc:
- '570'
- '576'
department:
- _id: CaGu
- _id: JoBo
doi: 10.1093/molbev/msv269
ec_funded: 1
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
has_accepted_license: '1'
intvolume: ' 33'
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: 3E5EF7F0-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.
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: 2021-01-12T06:47:37Z
day: '05'
department:
- _id: CaGu
doi: 10.1021/acssynbio.6b00013
intvolume: ' 5'
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 5
year: '2016'
...
---
_id: '1220'
abstract:
- lang: eng
text: Theoretical and numerical aspects of aerodynamic efficiency of propulsion
systems coupled to the boundary layer of a fuselage are studied. We discuss the
effects of local flow fields, which are affected both by conservative flow acceleration
as well as total pressure losses, on the efficiency of boundary layer immersed
propulsion devices. We introduce the concept of a boundary layer retardation turbine
that helps reduce skin friction over the fuselage. We numerically investigate
efficiency gains offered by boundary layer and wake interacting devices. We discuss
the results in terms of a total energy consumption framework and show that efficiency
gains of any device depend on all the other elements of the propulsion system.
author:
- first_name: Gregor
full_name: Mikić, Gregor
last_name: Mikić
- first_name: Alex
full_name: Stoll, Alex
last_name: Stoll
- first_name: Joe
full_name: Bevirt, Joe
last_name: Bevirt
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Mark
full_name: Moore, Mark
last_name: Moore
citation:
ama: 'Mikić G, Stoll A, Bevirt J, Grah R, Moore M. Fuselage boundary layer ingestion
propulsion applied to a thin haul commuter aircraft for optimal efficiency. In:
AIAA; 2016:1-19. doi:10.2514/6.2016-3764'
apa: 'Mikić, G., Stoll, A., Bevirt, J., Grah, R., & Moore, M. (2016). Fuselage
boundary layer ingestion propulsion applied to a thin haul commuter aircraft for
optimal efficiency (pp. 1–19). Presented at the AIAA: Aviation Technology, Integration,
and Operations Conference, Washington, D.C., USA: AIAA. https://doi.org/10.2514/6.2016-3764'
chicago: Mikić, Gregor, Alex Stoll, Joe Bevirt, Rok Grah, and Mark Moore. “Fuselage
Boundary Layer Ingestion Propulsion Applied to a Thin Haul Commuter Aircraft for
Optimal Efficiency,” 1–19. AIAA, 2016. https://doi.org/10.2514/6.2016-3764.
ieee: 'G. Mikić, A. Stoll, J. Bevirt, R. Grah, and M. Moore, “Fuselage boundary
layer ingestion propulsion applied to a thin haul commuter aircraft for optimal
efficiency,” presented at the AIAA: Aviation Technology, Integration, and Operations
Conference, Washington, D.C., USA, 2016, pp. 1–19.'
ista: 'Mikić G, Stoll A, Bevirt J, Grah R, Moore M. 2016. Fuselage boundary layer
ingestion propulsion applied to a thin haul commuter aircraft for optimal efficiency.
AIAA: Aviation Technology, Integration, and Operations Conference, 1–19.'
mla: Mikić, Gregor, et al. Fuselage Boundary Layer Ingestion Propulsion Applied
to a Thin Haul Commuter Aircraft for Optimal Efficiency. AIAA, 2016, pp. 1–19,
doi:10.2514/6.2016-3764.
short: G. Mikić, A. Stoll, J. Bevirt, R. Grah, M. Moore, in:, AIAA, 2016, pp. 1–19.
conference:
end_date: 2016-06-17
location: Washington, D.C., USA
name: 'AIAA: Aviation Technology, Integration, and Operations Conference'
start_date: 2016-06-13
date_created: 2018-12-11T11:50:47Z
date_published: 2016-06-01T00:00:00Z
date_updated: 2023-02-21T10:17:50Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.2514/6.2016-3764
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://ntrs.nasa.gov/search.jsp?R=20160010167&hterms=Fuselage+boundary+layer+ingestion+propulsion+applied+thin+haul+commuter+aircraft+optimal+efficiency&qs=N%3D0%26Ntk%3DAll%26Ntt%3DFuselage%2520boundary%2520layer%2520ingestion%2520propulsion%2520applied%2520to%2520a%2520thin%2520haul%2520commuter%2520aircraft%2520for%2520optimal%2520efficiency%26Ntx%3Dmode%2520matchallpartial%26Nm%3D123%7CCollection%7CNASA%2520STI%7C%7C17%7CCollection%7CNACA
month: '06'
oa: 1
oa_version: Preprint
page: 1 - 19
publication_status: published
publisher: AIAA
publist_id: '6114'
quality_controlled: '1'
scopus_import: 1
status: public
title: Fuselage boundary layer ingestion propulsion applied to a thin haul commuter
aircraft for optimal efficiency
type: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
year: '2016'
...
---
_id: '1234'
abstract:
- lang: eng
text: We present a new algorithm for the statistical model checking of Markov chains
with respect to unbounded temporal properties, including full linear temporal
logic. The main idea is that we monitor each simulation run on the fly, in order
to detect quickly if a bottom strongly connected component is entered with high
probability, in which case the simulation run can be terminated early. As a result,
our simulation runs are often much shorter than required by termination bounds
that are computed a priori for a desired level of confidence on a large state
space. In comparison to previous algorithms for statistical model checking our
method is not only faster in many cases but also requires less information about
the system, namely, only the minimum transition probability that occurs in the
Markov chain. In addition, our method can be generalised to unbounded quantitative
properties such as mean-payoff bounds.
acknowledgement: "This research was funded in part by the European Research Council
(ERC) under\r\ngrant agreement 267989 (QUAREM), the Austrian Science Fund
\ (FWF) under\r\ngrants project S11402-N23 (RiSE) and Z211-N23 (Wittgenstein Award),
the Peo-\r\nple Programme (Marie Curie Actions) of the European Union’s Seventh
Framework\r\nProgramme (FP7/2007-2013) REA Grant No 291734, the SNSF Advanced Postdoc.\r\nMobility
Fellowship – grant number P300P2\r\n161067, and the Czech Science Foun-\r\ndation
under grant agreement P202/12/G061."
alternative_title:
- LNCS
author:
- first_name: Przemyslaw
full_name: Daca, Przemyslaw
id: 49351290-F248-11E8-B48F-1D18A9856A87
last_name: Daca
- 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: Jan
full_name: Kretinsky, Jan
id: 44CEF464-F248-11E8-B48F-1D18A9856A87
last_name: Kretinsky
orcid: 0000-0002-8122-2881
- first_name: Tatjana
full_name: Petrov, Tatjana
id: 3D5811FC-F248-11E8-B48F-1D18A9856A87
last_name: Petrov
orcid: 0000-0002-9041-0905
citation:
ama: 'Daca P, Henzinger TA, Kretinsky J, Petrov T. Faster statistical model checking
for unbounded temporal properties. In: Vol 9636. Springer; 2016:112-129. doi:10.1007/978-3-662-49674-9_7'
apa: 'Daca, P., Henzinger, T. A., Kretinsky, J., & Petrov, T. (2016). Faster
statistical model checking for unbounded temporal properties (Vol. 9636, pp. 112–129).
Presented at the TACAS: Tools and Algorithms for the Construction and Analysis
of Systems, Eindhoven, The Netherlands: Springer. https://doi.org/10.1007/978-3-662-49674-9_7'
chicago: Daca, Przemyslaw, Thomas A Henzinger, Jan Kretinsky, and Tatjana Petrov.
“Faster Statistical Model Checking for Unbounded Temporal Properties,” 9636:112–29.
Springer, 2016. https://doi.org/10.1007/978-3-662-49674-9_7.
ieee: 'P. Daca, T. A. Henzinger, J. Kretinsky, and T. Petrov, “Faster statistical
model checking for unbounded temporal properties,” presented at the TACAS: Tools
and Algorithms for the Construction and Analysis of Systems, Eindhoven, The Netherlands,
2016, vol. 9636, pp. 112–129.'
ista: 'Daca P, Henzinger TA, Kretinsky J, Petrov T. 2016. Faster statistical model
checking for unbounded temporal properties. TACAS: Tools and Algorithms for the
Construction and Analysis of Systems, LNCS, vol. 9636, 112–129.'
mla: Daca, Przemyslaw, et al. Faster Statistical Model Checking for Unbounded
Temporal Properties. Vol. 9636, Springer, 2016, pp. 112–29, doi:10.1007/978-3-662-49674-9_7.
short: P. Daca, T.A. Henzinger, J. Kretinsky, T. Petrov, in:, Springer, 2016, pp.
112–129.
conference:
end_date: 2016-04-08
location: Eindhoven, The Netherlands
name: 'TACAS: Tools and Algorithms for the Construction and Analysis of Systems'
start_date: 2016-04-02
date_created: 2018-12-11T11:50:51Z
date_published: 2016-01-01T00:00:00Z
date_updated: 2023-09-07T11:58:33Z
day: '01'
department:
- _id: ToHe
- _id: CaGu
doi: 10.1007/978-3-662-49674-9_7
ec_funded: 1
intvolume: ' 9636'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1504.05739
month: '01'
oa: 1
oa_version: Preprint
page: 112 - 129
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: The Wittgenstein Prize
- _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: '6099'
quality_controlled: '1'
related_material:
record:
- id: '471'
relation: later_version
status: public
- id: '1155'
relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: Faster statistical model checking for unbounded temporal properties
type: conference
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 9636
year: '2016'
...
---
_id: '1243'
abstract:
- lang: eng
text: Restriction-modification (RM) systems represent a minimal and ubiquitous biological
system of self/non-self discrimination in prokaryotes [1], which protects hosts
from exogenous DNA [2]. The mechanism is based on the balance between methyltransferase
(M) and cognate restriction endonuclease (R). M tags endogenous DNA as self by
methylating short specific DNA sequences called restriction sites, whereas R recognizes
unmethylated restriction sites as non-self and introduces a double-stranded DNA
break [3]. Restriction sites are significantly underrepresented in prokaryotic
genomes [4-7], suggesting that the discrimination mechanism is imperfect and occasionally
leads to autoimmunity due to self-DNA cleavage (self-restriction) [8]. Furthermore,
RM systems can promote DNA recombination [9] and contribute to genetic variation
in microbial populations, thus facilitating adaptive evolution [10]. However,
cleavage of self-DNA by RM systems as elements shaping prokaryotic genomes has
not been directly detected, and its cause, frequency, and outcome are unknown.
We quantify self-restriction caused by two RM systems of Escherichia coli and
find that, in agreement with levels of restriction site avoidance, EcoRI, but
not EcoRV, cleaves self-DNA at a measurable rate. Self-restriction is a stochastic
process, which temporarily induces the SOS response, and is followed by DNA repair,
maintaining cell viability. We find that RM systems with higher restriction efficiency
against bacteriophage infections exhibit a higher rate of self-restriction, and
that this rate can be further increased by stochastic imbalance between R and
M. Our results identify molecular noise in RM systems as a factor shaping prokaryotic
genomes.
acknowledgement: This work was funded by an HFSP Young Investigators’ grant. M.P.
is a recipient of a DOC Fellowship of the Austrian Academy of Science at the Institute
of Science and Technology Austria. R.O. and Y.W. were supported by the Platform
for Dynamic Approaches to Living System from MEXT, Japan. We wish to thank I. Kobayashi
for providing us with the EcoRI and EcoRV plasmids, and A. Campbell for providing
us with the λ vir phage. We thank D. Siekhaus and C. Uhler and members of the C.C.G.
and J.P. Bollback laboratories for in-depth discussions. We thank B. Stern for comments
on an earlier version of the manuscript. We especially thank B.R. Levin for advice
and comments, and the anonymous reviewers for significantly improving the manuscript.
author:
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- first_name: Long
full_name: Qian, Long
last_name: Qian
- first_name: Reiko
full_name: Okura, Reiko
last_name: Okura
- first_name: Tobias
full_name: Bergmiller, Tobias
id: 2C471CFA-F248-11E8-B48F-1D18A9856A87
last_name: Bergmiller
orcid: 0000-0001-5396-4346
- first_name: Yuichi
full_name: Wakamoto, Yuichi
last_name: Wakamoto
- first_name: Edo
full_name: Kussell, Edo
last_name: Kussell
- first_name: Calin C
full_name: Guet, Calin C
id: 47F8433E-F248-11E8-B48F-1D18A9856A87
last_name: Guet
orcid: 0000-0001-6220-2052
citation:
ama: Pleska M, Qian L, Okura R, et al. Bacterial autoimmunity due to a restriction-modification
system. Current Biology. 2016;26(3):404-409. doi:10.1016/j.cub.2015.12.041
apa: Pleska, M., Qian, L., Okura, R., Bergmiller, T., Wakamoto, Y., Kussell, E.,
& Guet, C. C. (2016). Bacterial autoimmunity due to a restriction-modification
system. Current Biology. Cell Press. https://doi.org/10.1016/j.cub.2015.12.041
chicago: Pleska, Maros, Long Qian, Reiko Okura, Tobias Bergmiller, Yuichi Wakamoto,
Edo Kussell, and Calin C Guet. “Bacterial Autoimmunity Due to a Restriction-Modification
System.” Current Biology. Cell Press, 2016. https://doi.org/10.1016/j.cub.2015.12.041.
ieee: M. Pleska et al., “Bacterial autoimmunity due to a restriction-modification
system,” Current Biology, vol. 26, no. 3. Cell Press, pp. 404–409, 2016.
ista: Pleska M, Qian L, Okura R, Bergmiller T, Wakamoto Y, Kussell E, Guet CC. 2016.
Bacterial autoimmunity due to a restriction-modification system. Current Biology.
26(3), 404–409.
mla: Pleska, Maros, et al. “Bacterial Autoimmunity Due to a Restriction-Modification
System.” Current Biology, vol. 26, no. 3, Cell Press, 2016, pp. 404–09,
doi:10.1016/j.cub.2015.12.041.
short: M. Pleska, L. Qian, R. Okura, T. Bergmiller, Y. Wakamoto, E. Kussell, C.C.
Guet, Current Biology 26 (2016) 404–409.
date_created: 2018-12-11T11:50:54Z
date_published: 2016-02-08T00:00:00Z
date_updated: 2023-09-07T11:59:32Z
day: '08'
department:
- _id: CaGu
doi: 10.1016/j.cub.2015.12.041
intvolume: ' 26'
issue: '3'
language:
- iso: eng
month: '02'
oa_version: None
page: 404 - 409
project:
- _id: 251D65D8-B435-11E9-9278-68D0E5697425
grant_number: '24210'
name: Effects of Stochasticity on the Function of Restriction-Modi cation Systems
at the Single-Cell Level (DOC Fellowship)
publication: Current Biology
publication_status: published
publisher: Cell Press
publist_id: '6087'
quality_controlled: '1'
related_material:
record:
- id: '202'
relation: dissertation_contains
status: public
scopus_import: 1
status: public
title: Bacterial autoimmunity due to a restriction-modification system
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 26
year: '2016'
...
---
_id: '1250'
abstract:
- lang: eng
text: In bacteria, replicative aging manifests as a difference in growth or survival
between the two cells emerging from division. One cell can be regarded as an aging
mother with a decreased potential for future survival and division, the other
as a rejuvenated daughter. Here, we aimed at investigating some of the processes
involved in aging in the bacterium Escherichia coli, where the two types of cells
can be distinguished by the age of their cell poles. We found that certain changes
in the regulation of the carbohydrate metabolism can affect aging. A mutation
in the carbon storage regulator gene, csrA, leads to a dramatically shorter replicative
lifespan; csrA mutants stop dividing once their pole exceeds an age of about five
divisions. These old-pole cells accumulate glycogen at their old cell poles; after
their last division, they do not contain a chromosome, presumably because of spatial
exclusion by the glycogen aggregates. The new-pole daughters produced by these
aging mothers are born young; they only express the deleterious phenotype once
their pole is old. These results demonstrate how manipulations of nutrient allocation
can lead to the exclusion of the chromosome and limit replicative lifespan in
E. coli, and illustrate how mutations can have phenotypic effects that are specific
for cells with old poles. This raises the question how bacteria can avoid the
accumulation of such mutations in their genomes over evolutionary times, and how
they can achieve the long replicative lifespans that have recently been reported.
acknowledgement: This manuscript is dedicated to the memory of Alex Böhm, who was
a great friend and a passionate biologist. Alex passed away after the initial submission
of this manuscript. We thank Vesna Olivera and Ursula Sauder from the Zentrum für
Mikroskopie Uni Basel for excellent service, and Olin Silander, Nikki Freed, and
Nela Nikolic for helpful discussions. This work was supported by the Swiss National
Science Foundation grants to M. Ackermann and Urs Jenal (supporting AB).
article_number: e1005974
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. Genetic
manipulation of glycogen allocation affects replicative lifespan in E coli. PLoS
Genetics. 2016;12(4). doi:10.1371/journal.pgen.1005974
apa: Boehm, A., Arnoldini, M., Bergmiller, T., Röösli, T., Bigosch, C., & Ackermann,
M. (2016). Genetic manipulation of glycogen allocation affects replicative lifespan
in E coli. PLoS Genetics. Public Library of Science. https://doi.org/10.1371/journal.pgen.1005974
chicago: Boehm, Alex, Markus Arnoldini, Tobias Bergmiller, Thomas Röösli, Colette
Bigosch, and Martin Ackermann. “Genetic Manipulation of Glycogen Allocation Affects
Replicative Lifespan in E Coli.” PLoS Genetics. Public Library of Science,
2016. https://doi.org/10.1371/journal.pgen.1005974.
ieee: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, and M. Ackermann,
“Genetic manipulation of glycogen allocation affects replicative lifespan in E
coli,” PLoS Genetics, vol. 12, no. 4. Public Library of Science, 2016.
ista: Boehm A, Arnoldini M, Bergmiller T, Röösli T, Bigosch C, Ackermann M. 2016.
Genetic manipulation of glycogen allocation affects replicative lifespan in E
coli. PLoS Genetics. 12(4), e1005974.
mla: Boehm, Alex, et al. “Genetic Manipulation of Glycogen Allocation Affects Replicative
Lifespan in E Coli.” PLoS Genetics, vol. 12, no. 4, e1005974, Public Library
of Science, 2016, doi:10.1371/journal.pgen.1005974.
short: A. Boehm, M. Arnoldini, T. Bergmiller, T. Röösli, C. Bigosch, M. Ackermann,
PLoS Genetics 12 (2016).
date_created: 2018-12-11T11:50:56Z
date_published: 2016-04-19T00:00:00Z
date_updated: 2023-02-23T14:11:39Z
day: '19'
ddc:
- '576'
- '579'
department:
- _id: CaGu
doi: 10.1371/journal.pgen.1005974
file:
- access_level: open_access
checksum: 53d22b2b39e5adc243d34f18b2615a85
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:14:17Z
date_updated: 2020-07-14T12:44:41Z
file_id: '5067'
file_name: IST-2016-705-v1+1_journal.pgen.1005974.PDF
file_size: 6273249
relation: main_file
file_date_updated: 2020-07-14T12:44:41Z
has_accepted_license: '1'
intvolume: ' 12'
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Published Version
publication: PLoS Genetics
publication_status: published
publisher: Public Library of Science
publist_id: '6077'
pubrep_id: '705'
quality_controlled: '1'
related_material:
record:
- id: '9873'
relation: research_data
status: public
scopus_import: 1
status: public
title: Genetic manipulation of glycogen allocation affects replicative lifespan in
E coli
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: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 12
year: '2016'
...
---
_id: '1290'
abstract:
- lang: eng
text: We developed a competition-based screening strategy to identify compounds
that invert the selective advantage of antibiotic resistance. Using our assay,
we screened over 19,000 compounds for the ability to select against the TetA tetracycline-resistance
efflux pump in Escherichia coli and identified two hits, β-thujaplicin and disulfiram.
Treating a tetracycline-resistant population with β-thujaplicin selects for loss
of the resistance gene, enabling an effective second-phase treatment with doxycycline.
acknowledgement: "This work was supported in part by National Institute of Allergy
and Infectious Diseases grant U54 AI057159, US National Institutes of Health grants
R01 GM081617 (to R.K.) and GM086258 (to J.C.), European Research Council FP7 ERC
grant 281891 (to R.K.) and a National Science Foundation Graduate Fellowship (to
L.K.S.).\r\n"
author:
- first_name: Laura
full_name: Stone, Laura
last_name: Stone
- first_name: Michael
full_name: Baym, Michael
last_name: Baym
- first_name: Tami
full_name: Lieberman, Tami
last_name: Lieberman
- first_name: Remy P
full_name: Chait, Remy P
id: 3464AE84-F248-11E8-B48F-1D18A9856A87
last_name: Chait
orcid: 0000-0003-0876-3187
- first_name: Jon
full_name: Clardy, Jon
last_name: Clardy
- first_name: Roy
full_name: Kishony, Roy
last_name: Kishony
citation:
ama: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. Compounds that
select against the tetracycline-resistance efflux pump. Nature Chemical Biology.
2016;12(11):902-904. doi:10.1038/nchembio.2176
apa: Stone, L., Baym, M., Lieberman, T., Chait, R. P., Clardy, J., & Kishony,
R. (2016). Compounds that select against the tetracycline-resistance efflux pump.
Nature Chemical Biology. Nature Publishing Group. https://doi.org/10.1038/nchembio.2176
chicago: Stone, Laura, Michael Baym, Tami Lieberman, Remy P Chait, Jon Clardy, and
Roy Kishony. “Compounds That Select against the Tetracycline-Resistance Efflux
Pump.” Nature Chemical Biology. Nature Publishing Group, 2016. https://doi.org/10.1038/nchembio.2176.
ieee: L. Stone, M. Baym, T. Lieberman, R. P. Chait, J. Clardy, and R. Kishony, “Compounds
that select against the tetracycline-resistance efflux pump,” Nature Chemical
Biology, vol. 12, no. 11. Nature Publishing Group, pp. 902–904, 2016.
ista: Stone L, Baym M, Lieberman T, Chait RP, Clardy J, Kishony R. 2016. Compounds
that select against the tetracycline-resistance efflux pump. Nature Chemical Biology.
12(11), 902–904.
mla: Stone, Laura, et al. “Compounds That Select against the Tetracycline-Resistance
Efflux Pump.” Nature Chemical Biology, vol. 12, no. 11, Nature Publishing
Group, 2016, pp. 902–04, doi:10.1038/nchembio.2176.
short: L. Stone, M. Baym, T. Lieberman, R.P. Chait, J. Clardy, R. Kishony, Nature
Chemical Biology 12 (2016) 902–904.
date_created: 2018-12-11T11:51:10Z
date_published: 2016-11-01T00:00:00Z
date_updated: 2021-01-12T06:49:39Z
day: '01'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1038/nchembio.2176
intvolume: ' 12'
issue: '11'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5069154/
month: '11'
oa: 1
oa_version: Preprint
page: 902 - 904
publication: Nature Chemical Biology
publication_status: published
publisher: Nature Publishing Group
publist_id: '6026'
quality_controlled: '1'
scopus_import: 1
status: public
title: Compounds that select against the tetracycline-resistance efflux pump
type: journal_article
user_id: 3E5EF7F0-F248-11E8-B48F-1D18A9856A87
volume: 12
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: 2023-02-21T16:50:13Z
day: '19'
department:
- _id: CaGu
doi: 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'
...
---
_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.
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: 2023-09-07T11:53:49Z
day: '06'
ddc:
- '576'
department:
- _id: NiBa
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pgen.1005639
ec_funded: 1
file:
- access_level: open_access
checksum: a4e72fca5ccf40ddacf4d08c8e46b554
content_type: application/pdf
creator: system
date_created: 2018-12-12T10:07:58Z
date_updated: 2020-07-14T12:45:10Z
file_id: '4657'
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
has_accepted_license: '1'
intvolume: ' 11'
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
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
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: 2025-05-28T11:57:04Z
day: '01'
department:
- _id: ToHe
- _id: CaGu
- _id: NiBa
doi: 10.1007/978-3-662-46681-0_47
ec_funded: 1
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: The Wittgenstein Prize
- _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"
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: 2021-01-12T06:53:33Z
day: '01'
department:
- _id: CaGu
- _id: ToHe
doi: 10.1109/TAC.2014.2364971
intvolume: ' 60'
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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
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. '
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.
date_created: 2018-12-11T11:52:37Z
date_published: 2015-10-21T00:00:00Z
date_updated: 2021-01-12T06:51:29Z
day: '21'
ddc:
- '570'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1016/j.jtbi.2015.07.011
ec_funded: 1
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'
file_name: IST-2016-483-v1+1_1-s2.0-S0022519315003409-main.pdf
file_size: 595307
relation: main_file
file_date_updated: 2020-07-14T12:45:01Z
has_accepted_license: '1'
intvolume: ' 383'
language:
- iso: eng
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:
image: /images/cc_by_nc_nd.png
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: '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.
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: 2021-01-12T06:50:41Z
day: '11'
department:
- _id: NiBa
- _id: CaGu
doi: 10.1145/2739480.2754758
ec_funded: 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: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2015'
...