---
_id: '7673'
abstract:
- lang: eng
text: Combining drugs can improve the efficacy of treatments. However, predicting
the effect of drug combinations is still challenging. The combined potency of
drugs determines the drug interaction, which is classified as synergistic, additive,
antagonistic, or suppressive. While probabilistic, non-mechanistic models exist,
there is currently no biophysical model that can predict antibiotic interactions.
Here, we present a physiologically relevant model of the combined action of antibiotics
that inhibit protein synthesis by targeting the ribosome. This model captures
the kinetics of antibiotic binding and transport, and uses bacterial growth laws
to predict growth in the presence of antibiotic combinations. We find that this
biophysical model can produce all drug interaction types except suppression. We
show analytically that antibiotics which cannot bind to the ribosome simultaneously
generally act as substitutes for one another, leading to additive drug interactions.
Previously proposed null expectations for higher-order drug interactions follow
as a limiting case of our model. We further extend the model to include the effects
of direct physical or allosteric interactions between individual drugs on the
ribosome. Notably, such direct interactions profoundly change the combined drug
effect, depending on the kinetic parameters of the drugs used. The model makes
additional predictions for the effects of resistance genes on drug interactions
and for interactions between ribosome-targeting antibiotics and antibiotics with
other targets. These findings enhance our understanding of the interplay between
drug action and cell physiology and are a key step toward a general framework
for predicting drug interactions.
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- first_name: Tobias
full_name: Bollenbach, Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Kavcic B, Tkačik G, Bollenbach MT. A minimal biophysical model of combined
antibiotic action. bioRxiv. 2020. doi:10.1101/2020.04.18.047886
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). A minimal biophysical
model of combined antibiotic action. bioRxiv. Cold Spring Harbor Laboratory.
https://doi.org/10.1101/2020.04.18.047886
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “A Minimal Biophysical
Model of Combined Antibiotic Action.” BioRxiv. Cold Spring Harbor Laboratory,
2020. https://doi.org/10.1101/2020.04.18.047886.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “A minimal biophysical model of
combined antibiotic action,” bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. A minimal biophysical model of combined
antibiotic action. bioRxiv, 10.1101/2020.04.18.047886.
mla: Kavcic, Bor, et al. “A Minimal Biophysical Model of Combined Antibiotic Action.”
BioRxiv, Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.18.047886.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, BioRxiv (2020).
date_created: 2020-04-22T08:27:56Z
date_published: 2020-04-18T00:00:00Z
date_updated: 2024-03-25T23:30:05Z
day: '18'
department:
- _id: GaTk
doi: 10.1101/2020.04.18.047886
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.18.047886 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8997'
relation: later_version
status: public
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: A minimal biophysical model of combined antibiotic action
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '7675'
abstract:
- lang: eng
text: 'In prokaryotes, thermodynamic models of gene regulation provide a highly
quantitative mapping from promoter sequences to gene expression levels that is
compatible with in vivo and in vitro bio-physical measurements. Such concordance
has not been achieved for models of enhancer function in eukaryotes. In equilibrium
models, it is difficult to reconcile the reported short transcription factor (TF)
residence times on the DNA with the high specificity of regulation. In non-equilibrium
models, progress is difficult due to an explosion in the number of parameters.
Here, we navigate this complexity by looking for minimal non-equilibrium enhancer
models that yield desired regulatory phenotypes: low TF residence time, high specificity
and tunable cooperativity. We find that a single extra parameter, interpretable
as the “linking rate” by which bound TFs interact with Mediator components, enables
our models to escape equilibrium bounds and access optimal regulatory phenotypes,
while remaining consistent with the reported phenomenology and simple enough to
be inferred from upcoming experiments. We further find that high specificity in
non-equilibrium models is in a tradeoff with gene expression noise, predicting
bursty dynamics — an experimentally-observed hallmark of eukaryotic transcription.
By drastically reducing the vast parameter space to a much smaller subspace that
optimally realizes biological function prior to inference from data, our normative
approach holds promise for mathematical models in systems biology.'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Benjamin
full_name: Zoller, Benjamin
last_name: Zoller
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Grah R, Zoller B, Tkačik G. Normative models of enhancer function. bioRxiv.
2020. doi:10.1101/2020.04.08.029405
apa: Grah, R., Zoller, B., & Tkačik, G. (2020). Normative models of enhancer
function. bioRxiv. Cold Spring Harbor Laboratory. https://doi.org/10.1101/2020.04.08.029405
chicago: Grah, Rok, Benjamin Zoller, and Gašper Tkačik. “Normative Models of Enhancer
Function.” BioRxiv. Cold Spring Harbor Laboratory, 2020. https://doi.org/10.1101/2020.04.08.029405.
ieee: R. Grah, B. Zoller, and G. Tkačik, “Normative models of enhancer function,”
bioRxiv. Cold Spring Harbor Laboratory, 2020.
ista: Grah R, Zoller B, Tkačik G. 2020. Normative models of enhancer function. bioRxiv,
10.1101/2020.04.08.029405.
mla: Grah, Rok, et al. “Normative Models of Enhancer Function.” BioRxiv,
Cold Spring Harbor Laboratory, 2020, doi:10.1101/2020.04.08.029405.
short: R. Grah, B. Zoller, G. Tkačik, BioRxiv (2020).
date_created: 2020-04-23T10:12:51Z
date_published: 2020-04-09T00:00:00Z
date_updated: 2023-09-07T13:13:26Z
day: '09'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1101/2020.04.08.029405
language:
- iso: eng
main_file_link:
- open_access: '1'
url: 'https://doi.org/10.1101/2020.04.08.029405 '
month: '04'
oa: 1
oa_version: Preprint
project:
- _id: 2665AAFE-B435-11E9-9278-68D0E5697425
grant_number: RGP0034/2018
name: Can evolution minimize spurious signaling crosstalk to reach optimal performance?
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: bioRxiv
publication_status: published
publisher: Cold Spring Harbor Laboratory
related_material:
record:
- id: '8155'
relation: dissertation_contains
status: public
status: public
title: Normative models of enhancer function
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8084'
abstract:
- lang: eng
text: Origin and functions of intermittent transitions among sleep stages, including
brief awakenings and arousals, constitute a challenge to the current homeostatic
framework for sleep regulation, focusing on factors modulating sleep over large
time scales. Here we propose that the complex micro-architecture characterizing
sleep on scales of seconds and minutes results from intrinsic non-equilibrium
critical dynamics. We investigate θ- and δ-wave dynamics in control rats and in
rats where the sleep-promoting ventrolateral preoptic nucleus (VLPO) is lesioned
(male Sprague-Dawley rats). We demonstrate that bursts in θ and δ cortical rhythms
exhibit complex temporal organization, with long-range correlations and robust
duality of power-law (θ-bursts, active phase) and exponential-like (δ-bursts,
quiescent phase) duration distributions, features typical of non-equilibrium systems
self-organizing at criticality. We show that such non-equilibrium behavior relates
to anti-correlated coupling between θ- and δ-bursts, persists across a range of
time scales, and is independent of the dominant physiologic state; indications
of a basic principle in sleep regulation. Further, we find that VLPO lesions lead
to a modulation of cortical dynamics resulting in altered dynamical parameters
of θ- and δ-bursts and significant reduction in θ–δ coupling. Our empirical findings
and model simulations demonstrate that θ–δ coupling is essential for the emerging
non-equilibrium critical dynamics observed across the sleep–wake cycle, and indicate
that VLPO neurons may have dual role for both sleep and arousal/brief wake activation.
The uncovered critical behavior in sleep- and wake-related cortical rhythms indicates
a mechanism essential for the micro-architecture of spontaneous sleep-stage and
arousal transitions within a novel, non-homeostatic paradigm of sleep regulation.
article_processing_charge: No
article_type: original
author:
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Manuel
full_name: Gómez-Extremera, Manuel
last_name: Gómez-Extremera
- first_name: Pedro
full_name: Bernaola-Galván, Pedro
last_name: Bernaola-Galván
- first_name: Ramalingam
full_name: Vetrivelan, Ramalingam
last_name: Vetrivelan
- first_name: Clifford B.
full_name: Saper, Clifford B.
last_name: Saper
- first_name: Thomas E.
full_name: Scammell, Thomas E.
last_name: Scammell
- first_name: Plamen Ch.
full_name: Ivanov, Plamen Ch.
last_name: Ivanov
citation:
ama: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, et al. Critical dynamics
and coupling in bursts of cortical rhythms indicate non-homeostatic mechanism
for sleep-stage transitions and dual role of VLPO neurons in both sleep and wake.
Journal of Neuroscience. 2020;40(1):171-190. doi:10.1523/jneurosci.1278-19.2019
apa: Lombardi, F., Gómez-Extremera, M., Bernaola-Galván, P., Vetrivelan, R., Saper,
C. B., Scammell, T. E., & Ivanov, P. C. (2020). Critical dynamics and coupling
in bursts of cortical rhythms indicate non-homeostatic mechanism for sleep-stage
transitions and dual role of VLPO neurons in both sleep and wake. Journal of
Neuroscience. Society for Neuroscience. https://doi.org/10.1523/jneurosci.1278-19.2019
chicago: Lombardi, Fabrizio, Manuel Gómez-Extremera, Pedro Bernaola-Galván, Ramalingam
Vetrivelan, Clifford B. Saper, Thomas E. Scammell, and Plamen Ch. Ivanov. “Critical
Dynamics and Coupling in Bursts of Cortical Rhythms Indicate Non-Homeostatic Mechanism
for Sleep-Stage Transitions and Dual Role of VLPO Neurons in Both Sleep and Wake.”
Journal of Neuroscience. Society for Neuroscience, 2020. https://doi.org/10.1523/jneurosci.1278-19.2019.
ieee: F. Lombardi et al., “Critical dynamics and coupling in bursts of cortical
rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
role of VLPO neurons in both sleep and wake,” Journal of Neuroscience,
vol. 40, no. 1. Society for Neuroscience, pp. 171–190, 2020.
ista: Lombardi F, Gómez-Extremera M, Bernaola-Galván P, Vetrivelan R, Saper CB,
Scammell TE, Ivanov PC. 2020. Critical dynamics and coupling in bursts of cortical
rhythms indicate non-homeostatic mechanism for sleep-stage transitions and dual
role of VLPO neurons in both sleep and wake. Journal of Neuroscience. 40(1), 171–190.
mla: Lombardi, Fabrizio, et al. “Critical Dynamics and Coupling in Bursts of Cortical
Rhythms Indicate Non-Homeostatic Mechanism for Sleep-Stage Transitions and Dual
Role of VLPO Neurons in Both Sleep and Wake.” Journal of Neuroscience,
vol. 40, no. 1, Society for Neuroscience, 2020, pp. 171–90, doi:10.1523/jneurosci.1278-19.2019.
short: F. Lombardi, M. Gómez-Extremera, P. Bernaola-Galván, R. Vetrivelan, C.B.
Saper, T.E. Scammell, P.C. Ivanov, Journal of Neuroscience 40 (2020) 171–190.
date_created: 2020-07-05T15:24:51Z
date_published: 2020-01-02T00:00:00Z
date_updated: 2023-09-05T14:02:55Z
day: '02'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1523/jneurosci.1278-19.2019
ec_funded: 1
external_id:
isi:
- '000505167600016'
pmid:
- '31694962'
file:
- access_level: open_access
content_type: application/pdf
creator: dernst
date_created: 2020-07-22T11:44:48Z
date_updated: 2020-07-22T11:44:48Z
file_id: '8150'
file_name: 2020_JournNeuroscience_Lombardi.pdf
file_size: 6646046
relation: main_file
success: 1
file_date_updated: 2020-07-22T11:44:48Z
has_accepted_license: '1'
intvolume: ' 40'
isi: 1
issue: '1'
language:
- iso: eng
month: '01'
oa: 1
oa_version: Published Version
page: 171-190
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: Journal of Neuroscience
publication_identifier:
eissn:
- 1529-2401
issn:
- 0270-6474
publication_status: published
publisher: Society for Neuroscience
quality_controlled: '1'
scopus_import: '1'
status: public
title: Critical dynamics and coupling in bursts of cortical rhythms indicate non-homeostatic
mechanism for sleep-stage transitions and dual role of VLPO neurons in both sleep
and wake
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 40
year: '2020'
...
---
_id: '8097'
abstract:
- lang: eng
text: 'Antibiotics that interfere with translation, when combined, interact in diverse
and difficult-to-predict ways. Here, we explain these interactions by "translation
bottlenecks": points in the translation cycle where antibiotics block ribosomal
progression. To elucidate the underlying mechanisms of drug interactions between
translation inhibitors, we generate translation bottlenecks genetically using
inducible control of translation factors that regulate well-defined translation
cycle steps. These perturbations accurately mimic antibiotic action and drug interactions,
supporting that the interplay of different translation bottlenecks causes these
interactions. We further show that growth laws, combined with drug uptake and
binding kinetics, enable the direct prediction of a large fraction of observed
interactions, yet fail to predict suppression. However, varying two translation
bottlenecks simultaneously supports that dense traffic of ribosomes and competition
for translation factors account for the previously unexplained suppression. These
results highlight the importance of "continuous epistasis" in bacterial physiology.'
acknowledged_ssus:
- _id: LifeSc
article_processing_charge: No
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
citation:
ama: Kavcic B. Analysis scripts and research data for the paper “Mechanisms of drug
interactions between translation-inhibiting antibiotics.” 2020. doi:10.15479/AT:ISTA:8097
apa: Kavcic, B. (2020). Analysis scripts and research data for the paper “Mechanisms
of drug interactions between translation-inhibiting antibiotics.” Institute of
Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8097
chicago: Kavcic, Bor. “Analysis Scripts and Research Data for the Paper ‘Mechanisms
of Drug Interactions between Translation-Inhibiting Antibiotics.’” Institute of
Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8097.
ieee: B. Kavcic, “Analysis scripts and research data for the paper ‘Mechanisms of
drug interactions between translation-inhibiting antibiotics.’” Institute of Science
and Technology Austria, 2020.
ista: Kavcic B. 2020. Analysis scripts and research data for the paper ‘Mechanisms
of drug interactions between translation-inhibiting antibiotics’, Institute of
Science and Technology Austria, 10.15479/AT:ISTA:8097.
mla: Kavcic, Bor. Analysis Scripts and Research Data for the Paper “Mechanisms
of Drug Interactions between Translation-Inhibiting Antibiotics.” Institute
of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8097.
short: B. Kavcic, (2020).
contributor:
- contributor_type: research_group
first_name: Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- contributor_type: research_group
first_name: Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
date_created: 2020-07-06T20:40:19Z
date_published: 2020-07-15T00:00:00Z
date_updated: 2024-02-21T12:40:51Z
day: '15'
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8097
file:
- access_level: open_access
checksum: 5c321dbbb6d4b3c85da786fd3ebbdc98
content_type: application/zip
creator: bkavcic
date_created: 2020-07-06T20:38:27Z
date_updated: 2020-07-14T12:48:09Z
file_id: '8098'
file_name: natComm_2020_scripts.zip
file_size: 255770756
relation: main_file
file_date_updated: 2020-07-14T12:48:09Z
has_accepted_license: '1'
keyword:
- Escherichia coli
- antibiotic combinations
- translation
- growth laws
- drug interactions
- bacterial physiology
- translation inhibitors
month: '07'
oa: 1
oa_version: Published Version
publisher: Institute of Science and Technology Austria
status: public
title: Analysis scripts and research data for the paper "Mechanisms of drug interactions
between translation-inhibiting antibiotics"
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: research_data
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '8105'
abstract:
- lang: eng
text: Physical and biological systems often exhibit intermittent dynamics with bursts
or avalanches (active states) characterized by power-law size and duration distributions.
These emergent features are typical of systems at the critical point of continuous
phase transitions, and have led to the hypothesis that such systems may self-organize
at criticality, i.e. without any fine tuning of parameters. Since the introduction
of the Bak-Tang-Wiesenfeld (BTW) model, the paradigm of self-organized criticality
(SOC) has been very fruitful for the analysis of emergent collective behaviors
in a number of systems, including the brain. Although considerable effort has
been devoted in identifying and modeling scaling features of burst and avalanche
statistics, dynamical aspects related to the temporal organization of bursts remain
often poorly understood or controversial. Of crucial importance to understand
the mechanisms responsible for emergent behaviors is the relationship between
active and quiet periods, and the nature of the correlations. Here we investigate
the dynamics of active (θ-bursts) and quiet states (δ-bursts) in brain activity
during the sleep-wake cycle. We show the duality of power-law (θ, active phase)
and exponential-like (δ, quiescent phase) duration distributions, typical of SOC,
jointly emerge with power-law temporal correlations and anti-correlated coupling
between active and quiet states. Importantly, we demonstrate that such temporal
organization shares important similarities with earthquake dynamics, and propose
that specific power-law correlations and coupling between active and quiet states
are distinctive characteristics of a class of systems with self-organization at
criticality.
article_number: '00005'
article_processing_charge: No
article_type: original
author:
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Jilin W.J.L.
full_name: Wang, Jilin W.J.L.
last_name: Wang
- first_name: Xiyun
full_name: Zhang, Xiyun
last_name: Zhang
- first_name: Plamen Ch
full_name: Ivanov, Plamen Ch
last_name: Ivanov
citation:
ama: Lombardi F, Wang JWJL, Zhang X, Ivanov PC. Power-law correlations and coupling
of active and quiet states underlie a class of complex systems with self-organization
at criticality. EPJ Web of Conferences. 2020;230. doi:10.1051/epjconf/202023000005
apa: Lombardi, F., Wang, J. W. J. L., Zhang, X., & Ivanov, P. C. (2020). Power-law
correlations and coupling of active and quiet states underlie a class of complex
systems with self-organization at criticality. EPJ Web of Conferences.
EDP Sciences. https://doi.org/10.1051/epjconf/202023000005
chicago: Lombardi, Fabrizio, Jilin W.J.L. Wang, Xiyun Zhang, and Plamen Ch Ivanov.
“Power-Law Correlations and Coupling of Active and Quiet States Underlie a Class
of Complex Systems with Self-Organization at Criticality.” EPJ Web of Conferences.
EDP Sciences, 2020. https://doi.org/10.1051/epjconf/202023000005.
ieee: F. Lombardi, J. W. J. L. Wang, X. Zhang, and P. C. Ivanov, “Power-law correlations
and coupling of active and quiet states underlie a class of complex systems with
self-organization at criticality,” EPJ Web of Conferences, vol. 230. EDP
Sciences, 2020.
ista: Lombardi F, Wang JWJL, Zhang X, Ivanov PC. 2020. Power-law correlations and
coupling of active and quiet states underlie a class of complex systems with self-organization
at criticality. EPJ Web of Conferences. 230, 00005.
mla: Lombardi, Fabrizio, et al. “Power-Law Correlations and Coupling of Active and
Quiet States Underlie a Class of Complex Systems with Self-Organization at Criticality.”
EPJ Web of Conferences, vol. 230, 00005, EDP Sciences, 2020, doi:10.1051/epjconf/202023000005.
short: F. Lombardi, J.W.J.L. Wang, X. Zhang, P.C. Ivanov, EPJ Web of Conferences
230 (2020).
date_created: 2020-07-12T16:20:33Z
date_published: 2020-03-11T00:00:00Z
date_updated: 2021-01-12T08:16:55Z
day: '11'
ddc:
- '530'
department:
- _id: GaTk
doi: 10.1051/epjconf/202023000005
file:
- access_level: open_access
content_type: application/pdf
creator: dernst
date_created: 2020-07-22T06:17:11Z
date_updated: 2020-07-22T06:17:11Z
file_id: '8144'
file_name: 2020_EPJWebConf_Lombardi.pdf
file_size: 2197543
relation: main_file
success: 1
file_date_updated: 2020-07-22T06:17:11Z
has_accepted_license: '1'
intvolume: ' 230'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
publication: EPJ Web of Conferences
publication_identifier:
issn:
- 2100-014X
publication_status: published
publisher: EDP Sciences
quality_controlled: '1'
status: public
title: Power-law correlations and coupling of active and quiet states underlie a class
of complex systems with self-organization at criticality
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: 230
year: '2020'
...
---
_id: '8155'
abstract:
- lang: eng
text: "In the thesis we focus on the interplay of the biophysics and evolution of
gene regulation. We start by addressing how the type of prokaryotic gene regulation
– activation and repression – affects spurious binding to DNA, also known as\r\ntranscriptional
crosstalk. We propose that regulatory interference caused by excess regulatory
proteins in the dense cellular medium – global crosstalk – could be a factor in
determining which type of gene regulatory network is evolutionarily preferred.
Next,we use a normative approach in eukaryotic gene regulation to describe minimal\r\nnon-equilibrium
enhancer models that optimize so-called regulatory phenotypes. We find a class
of models that differ from standard thermodynamic equilibrium models by a single
parameter that notably increases the regulatory performance. Next chapter addresses
the question of genotype-phenotype-fitness maps of higher dimensional phenotypes.
We show that our biophysically realistic approach allows us to understand how
the mechanisms of promoter function constrain genotypephenotype maps, and how
they affect the evolutionary trajectories of promoters.\r\nIn the last chapter
we ask whether the intrinsic instability of gene duplication and amplification
provides a generic alternative to canonical gene regulation. Using mathematical
modeling, we show that amplifications can tune gene expression in many environments,
including those where transcription factor-based schemes are\r\nhard to evolve
or maintain. "
acknowledgement: For the duration of his PhD, Rok was a recipient of a DOC fellowship
of the Austrian Academy of Sciences.
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
citation:
ama: Grah R. Gene regulation across scales – how biophysical constraints shape evolution.
2020. doi:10.15479/AT:ISTA:8155
apa: Grah, R. (2020). Gene regulation across scales – how biophysical constraints
shape evolution. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8155
chicago: Grah, Rok. “Gene Regulation across Scales – How Biophysical Constraints
Shape Evolution.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8155.
ieee: R. Grah, “Gene regulation across scales – how biophysical constraints shape
evolution,” Institute of Science and Technology Austria, 2020.
ista: Grah R. 2020. Gene regulation across scales – how biophysical constraints
shape evolution. Institute of Science and Technology Austria.
mla: Grah, Rok. Gene Regulation across Scales – How Biophysical Constraints Shape
Evolution. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8155.
short: R. Grah, Gene Regulation across Scales – How Biophysical Constraints Shape
Evolution, Institute of Science and Technology Austria, 2020.
date_created: 2020-07-23T09:51:28Z
date_published: 2020-07-24T00:00:00Z
date_updated: 2023-09-07T13:13:27Z
day: '24'
ddc:
- '530'
- '570'
degree_awarded: PhD
department:
- _id: CaGu
- _id: GaTk
doi: 10.15479/AT:ISTA:8155
file:
- access_level: open_access
content_type: application/pdf
creator: rgrah
date_created: 2020-07-27T12:00:07Z
date_updated: 2020-07-27T12:00:07Z
file_id: '8176'
file_name: Thesis_RokGrah_200727_convertedNew.pdf
file_size: 16638998
relation: main_file
success: 1
- access_level: closed
content_type: application/zip
creator: rgrah
date_created: 2020-07-27T12:02:23Z
date_updated: 2020-07-30T13:04:55Z
file_id: '8177'
file_name: Thesis_new.zip
file_size: 347459978
relation: main_file
file_date_updated: 2020-07-30T13:04:55Z
has_accepted_license: '1'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
page: '310'
project:
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7675'
relation: part_of_dissertation
status: public
- id: '7569'
relation: part_of_dissertation
status: public
- id: '7652'
relation: part_of_dissertation
status: public
status: public
supervisor:
- 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: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
title: Gene regulation across scales – how biophysical constraints shape evolution
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '9776'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Supporting information. 2020. doi:10.1371/journal.pcbi.1007642.s001
apa: Grah, R., & Friedlander, T. (2020). Supporting information. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642.s001
chicago: Grah, Rok, and Tamar Friedlander. “Supporting Information.” Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s001.
ieee: R. Grah and T. Friedlander, “Supporting information.” Public Library of Science,
2020.
ista: Grah R, Friedlander T. 2020. Supporting information, Public Library of Science,
10.1371/journal.pcbi.1007642.s001.
mla: Grah, Rok, and Tamar Friedlander. Supporting Information. Public Library
of Science, 2020, doi:10.1371/journal.pcbi.1007642.s001.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:15:04Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-08-18T06:47:47Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s001
month: '02'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: used_in_publication
status: public
status: public
title: Supporting information
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '9777'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Maximizing crosstalk. 2020. doi:10.1371/journal.pcbi.1007642.s002
apa: Grah, R., & Friedlander, T. (2020). Maximizing crosstalk. Public Library
of Science. https://doi.org/10.1371/journal.pcbi.1007642.s002
chicago: Grah, Rok, and Tamar Friedlander. “Maximizing Crosstalk.” Public Library
of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s002.
ieee: R. Grah and T. Friedlander, “Maximizing crosstalk.” Public Library of Science,
2020.
ista: Grah R, Friedlander T. 2020. Maximizing crosstalk, Public Library of Science,
10.1371/journal.pcbi.1007642.s002.
mla: Grah, Rok, and Tamar Friedlander. Maximizing Crosstalk. Public Library
of Science, 2020, doi:10.1371/journal.pcbi.1007642.s002.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:21:51Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-09-12T11:02:25Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s002
main_file_link:
- open_access: '1'
url: https://doi.org/10.1371/journal.pcbi.1007642.s002
month: '02'
oa: 1
oa_version: None
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: used_in_publication
status: public
status: public
title: Maximizing crosstalk
type: research_data_reference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2020'
...
---
_id: '9779'
article_processing_charge: No
author:
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: Tamar
full_name: Friedlander, Tamar
last_name: Friedlander
citation:
ama: Grah R, Friedlander T. Distribution of crosstalk values. 2020. doi:10.1371/journal.pcbi.1007642.s003
apa: Grah, R., & Friedlander, T. (2020). Distribution of crosstalk values. Public
Library of Science. https://doi.org/10.1371/journal.pcbi.1007642.s003
chicago: Grah, Rok, and Tamar Friedlander. “Distribution of Crosstalk Values.” Public
Library of Science, 2020. https://doi.org/10.1371/journal.pcbi.1007642.s003.
ieee: R. Grah and T. Friedlander, “Distribution of crosstalk values.” Public Library
of Science, 2020.
ista: Grah R, Friedlander T. 2020. Distribution of crosstalk values, Public Library
of Science, 10.1371/journal.pcbi.1007642.s003.
mla: Grah, Rok, and Tamar Friedlander. Distribution of Crosstalk Values.
Public Library of Science, 2020, doi:10.1371/journal.pcbi.1007642.s003.
short: R. Grah, T. Friedlander, (2020).
date_created: 2021-08-06T07:24:37Z
date_published: 2020-02-25T00:00:00Z
date_updated: 2023-08-18T06:47:47Z
day: '25'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007642.s003
month: '02'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '7569'
relation: research_data
status: public
status: public
title: Distribution of crosstalk values
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
year: '2020'
...
---
_id: '7103'
abstract:
- lang: eng
text: Origin and functions of intermittent transitions among sleep stages, including
short awakenings and arousals, constitute a challenge to the current homeostatic
framework for sleep regulation, focusing on factors modulating sleep over large
time scales. Here we propose that the complex micro-architecture characterizing
the sleep-wake cycle results from an underlying non-equilibrium critical dynamics,
bridging collective behaviors across spatio-temporal scales. We investigate θ
and δ wave dynamics in control rats and in rats with lesions of sleep-promoting
neurons in the parafacial zone. We demonstrate that intermittent bursts in θ and
δ rhythms exhibit a complex temporal organization, with long-range power-law correlations
and a robust duality of power law (θ-bursts, active phase) and exponential-like
(δ-bursts, quiescent phase) duration distributions, typical features of non-equilibrium
systems self-organizing at criticality. Crucially, such temporal organization
relates to anti-correlated coupling between θ- and δ-bursts, and is independent
of the dominant physiologic state and lesions, a solid indication of a basic principle
in sleep dynamics.
article_number: e1007268
article_processing_charge: No
article_type: original
author:
- first_name: Jilin W. J. L.
full_name: Wang, Jilin W. J. L.
last_name: Wang
- first_name: Fabrizio
full_name: Lombardi, Fabrizio
id: A057D288-3E88-11E9-986D-0CF4E5697425
last_name: Lombardi
orcid: 0000-0003-2623-5249
- first_name: Xiyun
full_name: Zhang, Xiyun
last_name: Zhang
- first_name: Christelle
full_name: Anaclet, Christelle
last_name: Anaclet
- first_name: Plamen Ch.
full_name: Ivanov, Plamen Ch.
last_name: Ivanov
citation:
ama: Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. Non-equilibrium critical
dynamics of bursts in θ and δ rhythms as fundamental characteristic of sleep and
wake micro-architecture. PLoS Computational Biology. 2019;15(11). doi:10.1371/journal.pcbi.1007268
apa: Wang, J. W. J. L., Lombardi, F., Zhang, X., Anaclet, C., & Ivanov, P. C.
(2019). Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental
characteristic of sleep and wake micro-architecture. PLoS Computational Biology.
Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007268
chicago: Wang, Jilin W. J. L., Fabrizio Lombardi, Xiyun Zhang, Christelle Anaclet,
and Plamen Ch. Ivanov. “Non-Equilibrium Critical Dynamics of Bursts in θ and δ
Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.” PLoS
Computational Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007268.
ieee: J. W. J. L. Wang, F. Lombardi, X. Zhang, C. Anaclet, and P. C. Ivanov, “Non-equilibrium
critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of
sleep and wake micro-architecture,” PLoS Computational Biology, vol. 15,
no. 11. Public Library of Science, 2019.
ista: Wang JWJL, Lombardi F, Zhang X, Anaclet C, Ivanov PC. 2019. Non-equilibrium
critical dynamics of bursts in θ and δ rhythms as fundamental characteristic of
sleep and wake micro-architecture. PLoS Computational Biology. 15(11), e1007268.
mla: Wang, Jilin W. J. L., et al. “Non-Equilibrium Critical Dynamics of Bursts in
θ and δ Rhythms as Fundamental Characteristic of Sleep and Wake Micro-Architecture.”
PLoS Computational Biology, vol. 15, no. 11, e1007268, Public Library of
Science, 2019, doi:10.1371/journal.pcbi.1007268.
short: J.W.J.L. Wang, F. Lombardi, X. Zhang, C. Anaclet, P.C. Ivanov, PLoS Computational
Biology 15 (2019).
date_created: 2019-11-25T08:20:47Z
date_published: 2019-11-01T00:00:00Z
date_updated: 2023-10-17T12:30:07Z
day: '01'
ddc:
- '570'
- '000'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007268
ec_funded: 1
external_id:
isi:
- '000500976100014'
pmid:
- '31725712'
file:
- access_level: open_access
checksum: 2a096a9c6dcc6eaa94077b2603bc6c12
content_type: application/pdf
creator: dernst
date_created: 2019-11-25T08:24:01Z
date_updated: 2020-07-14T12:47:49Z
file_id: '7104'
file_name: 2019_PLOSComBio_Wang.pdf
file_size: 3982516
relation: main_file
file_date_updated: 2020-07-14T12:47:49Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '11'
language:
- iso: eng
month: '11'
oa: 1
oa_version: Published Version
pmid: 1
project:
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: PLoS Computational Biology
publication_identifier:
issn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
scopus_import: '1'
status: public
title: Non-equilibrium critical dynamics of bursts in θ and δ rhythms as fundamental
characteristic of sleep and wake micro-architecture
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: 15
year: '2019'
...
---
_id: '7422'
abstract:
- lang: eng
text: Biochemical reactions often occur at low copy numbers but at once in crowded
and diverse environments. Space and stochasticity therefore play an essential
role in biochemical networks. Spatial-stochastic simulations have become a prominent
tool for understanding how stochasticity at the microscopic level influences the
macroscopic behavior of such systems. While particle-based models guarantee the
level of detail necessary to accurately describe the microscopic dynamics at very
low copy numbers, the algorithms used to simulate them typically imply trade-offs
between computational efficiency and biochemical accuracy. eGFRD (enhanced Green’s
Function Reaction Dynamics) is an exact algorithm that evades such trade-offs
by partitioning the N-particle system into M ≤ N analytically tractable one- and
two-particle systems; the analytical solutions (Green’s functions) then are used
to implement an event-driven particle-based scheme that allows particles to make
large jumps in time and space while retaining access to their state variables
at arbitrary simulation times. Here we present “eGFRD2,” a new eGFRD version that
implements the principle of eGFRD in all dimensions, thus enabling efficient particle-based
simulation of biochemical reaction-diffusion processes in the 3D cytoplasm, on
2D planes representing membranes, and on 1D elongated cylinders representative
of, e.g., cytoskeletal tracks or DNA; in 1D, it also incorporates convective motion
used to model active transport. We find that, for low particle densities, eGFRD2
is up to 6 orders of magnitude faster than conventional Brownian dynamics. We
exemplify the capabilities of eGFRD2 by simulating an idealized model of Pom1
gradient formation, which involves 3D diffusion, active transport on microtubules,
and autophosphorylation on the membrane, confirming recent experimental and theoretical
results on this system to hold under genuinely stochastic conditions.
article_number: '054108'
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Thomas R
full_name: Sokolowski, Thomas R
id: 3E999752-F248-11E8-B48F-1D18A9856A87
last_name: Sokolowski
orcid: 0000-0002-1287-3779
- first_name: Joris
full_name: Paijmans, Joris
last_name: Paijmans
- first_name: Laurens
full_name: Bossen, Laurens
last_name: Bossen
- first_name: Thomas
full_name: Miedema, Thomas
last_name: Miedema
- first_name: Martijn
full_name: Wehrens, Martijn
last_name: Wehrens
- first_name: Nils B.
full_name: Becker, Nils B.
last_name: Becker
- first_name: Kazunari
full_name: Kaizu, Kazunari
last_name: Kaizu
- first_name: Koichi
full_name: Takahashi, Koichi
last_name: Takahashi
- first_name: Marileen
full_name: Dogterom, Marileen
last_name: Dogterom
- first_name: Pieter Rein
full_name: ten Wolde, Pieter Rein
last_name: ten Wolde
citation:
ama: Sokolowski TR, Paijmans J, Bossen L, et al. eGFRD in all dimensions. The
Journal of Chemical Physics. 2019;150(5). doi:10.1063/1.5064867
apa: Sokolowski, T. R., Paijmans, J., Bossen, L., Miedema, T., Wehrens, M., Becker,
N. B., … ten Wolde, P. R. (2019). eGFRD in all dimensions. The Journal of Chemical
Physics. AIP Publishing. https://doi.org/10.1063/1.5064867
chicago: Sokolowski, Thomas R, Joris Paijmans, Laurens Bossen, Thomas Miedema, Martijn
Wehrens, Nils B. Becker, Kazunari Kaizu, Koichi Takahashi, Marileen Dogterom,
and Pieter Rein ten Wolde. “EGFRD in All Dimensions.” The Journal of Chemical
Physics. AIP Publishing, 2019. https://doi.org/10.1063/1.5064867.
ieee: T. R. Sokolowski et al., “eGFRD in all dimensions,” The Journal
of Chemical Physics, vol. 150, no. 5. AIP Publishing, 2019.
ista: Sokolowski TR, Paijmans J, Bossen L, Miedema T, Wehrens M, Becker NB, Kaizu
K, Takahashi K, Dogterom M, ten Wolde PR. 2019. eGFRD in all dimensions. The Journal
of Chemical Physics. 150(5), 054108.
mla: Sokolowski, Thomas R., et al. “EGFRD in All Dimensions.” The Journal of
Chemical Physics, vol. 150, no. 5, 054108, AIP Publishing, 2019, doi:10.1063/1.5064867.
short: T.R. Sokolowski, J. Paijmans, L. Bossen, T. Miedema, M. Wehrens, N.B. Becker,
K. Kaizu, K. Takahashi, M. Dogterom, P.R. ten Wolde, The Journal of Chemical Physics
150 (2019).
date_created: 2020-01-30T10:34:36Z
date_published: 2019-02-07T00:00:00Z
date_updated: 2023-09-06T14:59:28Z
day: '07'
department:
- _id: GaTk
doi: 10.1063/1.5064867
external_id:
arxiv:
- '1708.09364'
isi:
- '000458109300009'
intvolume: ' 150'
isi: 1
issue: '5'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1708.09364
month: '02'
oa: 1
oa_version: Preprint
publication: The Journal of Chemical Physics
publication_identifier:
eissn:
- 1089-7690
issn:
- 0021-9606
publication_status: published
publisher: AIP Publishing
quality_controlled: '1'
status: public
title: eGFRD in all dimensions
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 150
year: '2019'
...
---
_id: '7552'
abstract:
- lang: eng
text: 'There is increasing evidence that protein binding to specific sites along
DNA can activate the reading out of genetic information without coming into direct
physical contact with the gene. There also is evidence that these distant but
interacting sites are embedded in a liquid droplet of proteins which condenses
out of the surrounding solution. We argue that droplet-mediated interactions can
account for crucial features of gene regulation only if the droplet is poised
at a non-generic point in its phase diagram. We explore a minimal model that embodies
this idea, show that this model has a natural mechanism for self-tuning, and suggest
direct experimental tests. '
article_processing_charge: No
arxiv: 1
author:
- first_name: William
full_name: Bialek, William
last_name: Bialek
- first_name: Thomas
full_name: Gregor, Thomas
last_name: Gregor
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation.
arXiv:191208579.
apa: Bialek, W., Gregor, T., & Tkačik, G. (n.d.). Action at a distance in transcriptional
regulation. arXiv:1912.08579. ArXiv.
chicago: Bialek, William, Thomas Gregor, and Gašper Tkačik. “Action at a Distance
in Transcriptional Regulation.” ArXiv:1912.08579. ArXiv, n.d.
ieee: W. Bialek, T. Gregor, and G. Tkačik, “Action at a distance in transcriptional
regulation,” arXiv:1912.08579. ArXiv.
ista: Bialek W, Gregor T, Tkačik G. Action at a distance in transcriptional regulation.
arXiv:1912.08579, .
mla: Bialek, William, et al. “Action at a Distance in Transcriptional Regulation.”
ArXiv:1912.08579, ArXiv.
short: W. Bialek, T. Gregor, G. Tkačik, ArXiv:1912.08579 (n.d.).
date_created: 2020-02-28T10:57:08Z
date_published: 2019-12-18T00:00:00Z
date_updated: 2021-01-12T08:14:09Z
day: '18'
department:
- _id: GaTk
external_id:
arxiv:
- '1912.08579'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1912.08579
month: '12'
oa: 1
oa_version: Preprint
page: '5'
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: arXiv:1912.08579
publication_status: submitted
publisher: ArXiv
status: public
title: Action at a distance in transcriptional regulation
type: preprint
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2019'
...
---
_id: '7606'
abstract:
- lang: eng
text: We derive a tight lower bound on equivocation (conditional entropy), or equivalently
a tight upper bound on mutual information between a signal variable and channel
outputs. The bound is in terms of the joint distribution of the signals and maximum
a posteriori decodes (most probable signals given channel output). As part of
our derivation, we describe the key properties of the distribution of signals,
channel outputs and decodes, that minimizes equivocation and maximizes mutual
information. This work addresses a problem in data analysis, where mutual information
between signals and decodes is sometimes used to lower bound the mutual information
between signals and channel outputs. Our result provides a corresponding upper
bound.
article_number: '8989292'
article_processing_charge: No
arxiv: 1
author:
- first_name: Michal
full_name: Hledik, Michal
id: 4171253A-F248-11E8-B48F-1D18A9856A87
last_name: Hledik
- first_name: Thomas R
full_name: Sokolowski, Thomas R
id: 3E999752-F248-11E8-B48F-1D18A9856A87
last_name: Sokolowski
orcid: 0000-0002-1287-3779
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: 'Hledik M, Sokolowski TR, Tkačik G. A tight upper bound on mutual information.
In: IEEE Information Theory Workshop, ITW 2019. IEEE; 2019. doi:10.1109/ITW44776.2019.8989292'
apa: 'Hledik, M., Sokolowski, T. R., & Tkačik, G. (2019). A tight upper bound
on mutual information. In IEEE Information Theory Workshop, ITW 2019. Visby,
Sweden: IEEE. https://doi.org/10.1109/ITW44776.2019.8989292'
chicago: Hledik, Michal, Thomas R Sokolowski, and Gašper Tkačik. “A Tight Upper
Bound on Mutual Information.” In IEEE Information Theory Workshop, ITW 2019.
IEEE, 2019. https://doi.org/10.1109/ITW44776.2019.8989292.
ieee: M. Hledik, T. R. Sokolowski, and G. Tkačik, “A tight upper bound on mutual
information,” in IEEE Information Theory Workshop, ITW 2019, Visby, Sweden,
2019.
ista: Hledik M, Sokolowski TR, Tkačik G. 2019. A tight upper bound on mutual information.
IEEE Information Theory Workshop, ITW 2019. Information Theory Workshop, 8989292.
mla: Hledik, Michal, et al. “A Tight Upper Bound on Mutual Information.” IEEE
Information Theory Workshop, ITW 2019, 8989292, IEEE, 2019, doi:10.1109/ITW44776.2019.8989292.
short: M. Hledik, T.R. Sokolowski, G. Tkačik, in:, IEEE Information Theory Workshop,
ITW 2019, IEEE, 2019.
conference:
end_date: 2019-08-28
location: Visby, Sweden
name: Information Theory Workshop
start_date: 2019-08-25
date_created: 2020-03-22T23:00:47Z
date_published: 2019-08-01T00:00:00Z
date_updated: 2025-06-30T13:21:05Z
day: '01'
department:
- _id: GaTk
doi: 10.1109/ITW44776.2019.8989292
ec_funded: 1
external_id:
arxiv:
- '1812.01475'
isi:
- '000540384500015'
isi: 1
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://arxiv.org/abs/1812.01475
month: '08'
oa: 1
oa_version: Preprint
project:
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: IEEE Information Theory Workshop, ITW 2019
publication_identifier:
isbn:
- '9781538669006'
publication_status: published
publisher: IEEE
quality_controlled: '1'
related_material:
record:
- id: '15020'
relation: dissertation_contains
status: public
scopus_import: '1'
status: public
title: A tight upper bound on mutual information
type: conference
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '196'
abstract:
- lang: eng
text: 'The abelian sandpile serves as a model to study self-organized criticality,
a phenomenon occurring in biological, physical and social processes. The identity
of the abelian group is a fractal composed of self-similar patches, and its limit
is subject of extensive collaborative research. Here, we analyze the evolution
of the sandpile identity under harmonic fields of different orders. We show that
this evolution corresponds to periodic cycles through the abelian group characterized
by the smooth transformation and apparent conservation of the patches constituting
the identity. The dynamics induced by second and third order harmonics resemble
smooth stretchings, respectively translations, of the identity, while the ones
induced by fourth order harmonics resemble magnifications and rotations. Starting
with order three, the dynamics pass through extended regions of seemingly random
configurations which spontaneously reassemble into accentuated patterns. We show
that the space of harmonic functions projects to the extended analogue of the
sandpile group, thus providing a set of universal coordinates identifying configurations
between different domains. Since the original sandpile group is a subgroup of
the extended one, this directly implies that it admits a natural renormalization.
Furthermore, we show that the harmonic fields can be induced by simple Markov
processes, and that the corresponding stochastic dynamics show remarkable robustness
over hundreds of periods. Finally, we encode information into seemingly random
configurations, and decode this information with an algorithm requiring minimal
prior knowledge. Our results suggest that harmonic fields might split the sandpile
group into sub-sets showing different critical coefficients, and that it might
be possible to extend the fractal structure of the identity beyond the boundaries
of its domain. '
acknowledgement: "M.L. is grateful to the members of the C Guet and G Tkacik groups
for valuable comments and support. M.S. is grateful to Nikita Kalinin for inspiring
communications.\r\n"
article_processing_charge: No
article_type: original
arxiv: 1
author:
- first_name: Moritz
full_name: Lang, Moritz
id: 29E0800A-F248-11E8-B48F-1D18A9856A87
last_name: Lang
- first_name: Mikhail
full_name: Shkolnikov, Mikhail
id: 35084A62-F248-11E8-B48F-1D18A9856A87
last_name: Shkolnikov
orcid: 0000-0002-4310-178X
citation:
ama: Lang M, Shkolnikov M. Harmonic dynamics of the Abelian sandpile. Proceedings
of the National Academy of Sciences. 2019;116(8):2821-2830. doi:10.1073/pnas.1812015116
apa: Lang, M., & Shkolnikov, M. (2019). Harmonic dynamics of the Abelian sandpile.
Proceedings of the National Academy of Sciences. National Academy of Sciences.
https://doi.org/10.1073/pnas.1812015116
chicago: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian
Sandpile.” Proceedings of the National Academy of Sciences. National Academy
of Sciences, 2019. https://doi.org/10.1073/pnas.1812015116.
ieee: M. Lang and M. Shkolnikov, “Harmonic dynamics of the Abelian sandpile,” Proceedings
of the National Academy of Sciences, vol. 116, no. 8. National Academy of
Sciences, pp. 2821–2830, 2019.
ista: Lang M, Shkolnikov M. 2019. Harmonic dynamics of the Abelian sandpile. Proceedings
of the National Academy of Sciences. 116(8), 2821–2830.
mla: Lang, Moritz, and Mikhail Shkolnikov. “Harmonic Dynamics of the Abelian Sandpile.”
Proceedings of the National Academy of Sciences, vol. 116, no. 8, National
Academy of Sciences, 2019, pp. 2821–30, doi:10.1073/pnas.1812015116.
short: M. Lang, M. Shkolnikov, Proceedings of the National Academy of Sciences 116
(2019) 2821–2830.
date_created: 2018-12-11T11:45:08Z
date_published: 2019-02-19T00:00:00Z
date_updated: 2023-09-11T14:09:34Z
day: '19'
department:
- _id: CaGu
- _id: GaTk
- _id: TaHa
doi: 10.1073/pnas.1812015116
external_id:
arxiv:
- '1806.10823'
isi:
- '000459074400013'
pmid:
- ' 30728300'
intvolume: ' 116'
isi: 1
issue: '8'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1073/pnas.1812015116
month: '02'
oa: 1
oa_version: Published Version
page: 2821-2830
pmid: 1
publication: Proceedings of the National Academy of Sciences
publication_identifier:
eissn:
- 1091-6490
publication_status: published
publisher: National Academy of Sciences
quality_controlled: '1'
related_material:
link:
- description: News on IST Webpage
relation: press_release
url: https://ist.ac.at/en/news/famous-sandpile-model-shown-to-move-like-a-traveling-sand-dune/
scopus_import: '1'
status: public
title: Harmonic dynamics of the Abelian sandpile
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 116
year: '2019'
...
---
_id: '5817'
abstract:
- lang: eng
text: We theoretically study the shapes of lipid vesicles confined to a spherical
cavity, elaborating a framework based on the so-called limiting shapes constructed
from geometrically simple structural elements such as double-membrane walls and
edges. Partly inspired by numerical results, the proposed non-compartmentalized
and compartmentalized limiting shapes are arranged in the bilayer-couple phase
diagram which is then compared to its free-vesicle counterpart. We also compute
the area-difference-elasticity phase diagram of the limiting shapes and we use
it to interpret shape transitions experimentally observed in vesicles confined
within another vesicle. The limiting-shape framework may be generalized to theoretically
investigate the structure of certain cell organelles such as the mitochondrion.
article_processing_charge: No
article_type: original
author:
- first_name: Bor
full_name: Kavcic, Bor
id: 350F91D2-F248-11E8-B48F-1D18A9856A87
last_name: Kavcic
orcid: 0000-0001-6041-254X
- first_name: A.
full_name: Sakashita, A.
last_name: Sakashita
- first_name: H.
full_name: Noguchi, H.
last_name: Noguchi
- first_name: P.
full_name: Ziherl, P.
last_name: Ziherl
citation:
ama: Kavcic B, Sakashita A, Noguchi H, Ziherl P. Limiting shapes of confined lipid
vesicles. Soft Matter. 2019;15(4):602-614. doi:10.1039/c8sm01956h
apa: Kavcic, B., Sakashita, A., Noguchi, H., & Ziherl, P. (2019). Limiting shapes
of confined lipid vesicles. Soft Matter. Royal Society of Chemistry. https://doi.org/10.1039/c8sm01956h
chicago: Kavcic, Bor, A. Sakashita, H. Noguchi, and P. Ziherl. “Limiting Shapes
of Confined Lipid Vesicles.” Soft Matter. Royal Society of Chemistry, 2019.
https://doi.org/10.1039/c8sm01956h.
ieee: B. Kavcic, A. Sakashita, H. Noguchi, and P. Ziherl, “Limiting shapes of confined
lipid vesicles,” Soft Matter, vol. 15, no. 4. Royal Society of Chemistry,
pp. 602–614, 2019.
ista: Kavcic B, Sakashita A, Noguchi H, Ziherl P. 2019. Limiting shapes of confined
lipid vesicles. Soft Matter. 15(4), 602–614.
mla: Kavcic, Bor, et al. “Limiting Shapes of Confined Lipid Vesicles.” Soft Matter,
vol. 15, no. 4, Royal Society of Chemistry, 2019, pp. 602–14, doi:10.1039/c8sm01956h.
short: B. Kavcic, A. Sakashita, H. Noguchi, P. Ziherl, Soft Matter 15 (2019) 602–614.
date_created: 2019-01-11T07:37:47Z
date_published: 2019-01-10T00:00:00Z
date_updated: 2023-09-13T08:47:16Z
day: '10'
ddc:
- '530'
department:
- _id: GaTk
doi: 10.1039/c8sm01956h
external_id:
isi:
- '000457329700003'
pmid:
- '30629082'
file:
- access_level: open_access
checksum: 614c337d6424ccd3d48d1b1f9513510d
content_type: application/pdf
creator: bkavcic
date_created: 2020-10-09T11:00:05Z
date_updated: 2020-10-09T11:00:05Z
file_id: '8641'
file_name: lmt_sftmtr_V8.pdf
file_size: 5370762
relation: main_file
success: 1
file_date_updated: 2020-10-09T11:00:05Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '4'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc-nd/3.0/
month: '01'
oa: 1
oa_version: Submitted Version
page: 602-614
pmid: 1
publication: Soft Matter
publication_identifier:
eissn:
- 1744-6848
issn:
- 1744-683X
publication_status: published
publisher: Royal Society of Chemistry
quality_controlled: '1'
scopus_import: '1'
status: public
title: Limiting shapes of confined lipid vesicles
tmp:
image: /images/cc_by_nc_nd.png
legal_code_url: https://creativecommons.org/licenses/by-nc-nd/3.0/legalcode
name: Creative Commons Attribution-NonCommercial-NoDerivs 3.0 Unported (CC BY-NC-ND
3.0)
short: CC BY-NC-ND (3.0)
type: journal_article
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
volume: 15
year: '2019'
...
---
_id: '5945'
abstract:
- lang: eng
text: In developing organisms, spatially prescribed cell identities are thought
to be determined by the expression levels of multiple genes. Quantitative tests
of this idea, however, require a theoretical framework capable of exposing the
rules and precision of cell specification over developmental time. We use the
gap gene network in the early fly embryo as an example to show how expression
levels of the four gap genes can be jointly decoded into an optimal specification
of position with 1% accuracy. The decoder correctly predicts, with no free parameters,
the dynamics of pair-rule expression patterns at different developmental time
points and in various mutant backgrounds. Precise cellular identities are thus
available at the earliest stages of development, contrasting the prevailing view
of positional information being slowly refined across successive layers of the
patterning network. Our results suggest that developmental enhancers closely approximate
a mathematically optimal decoding strategy.
article_processing_charge: No
article_type: original
author:
- first_name: Mariela D.
full_name: Petkova, Mariela D.
last_name: Petkova
- first_name: Gasper
full_name: Tkacik, Gasper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkacik
orcid: 0000-0002-6699-1455
- first_name: William
full_name: Bialek, William
last_name: Bialek
- first_name: Eric F.
full_name: Wieschaus, Eric F.
last_name: Wieschaus
- first_name: Thomas
full_name: Gregor, Thomas
last_name: Gregor
citation:
ama: Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. Optimal decoding of
cellular identities in a genetic network. Cell. 2019;176(4):844-855.e15.
doi:10.1016/j.cell.2019.01.007
apa: Petkova, M. D., Tkačik, G., Bialek, W., Wieschaus, E. F., & Gregor, T.
(2019). Optimal decoding of cellular identities in a genetic network. Cell.
Cell Press. https://doi.org/10.1016/j.cell.2019.01.007
chicago: Petkova, Mariela D., Gašper Tkačik, William Bialek, Eric F. Wieschaus,
and Thomas Gregor. “Optimal Decoding of Cellular Identities in a Genetic Network.”
Cell. Cell Press, 2019. https://doi.org/10.1016/j.cell.2019.01.007.
ieee: M. D. Petkova, G. Tkačik, W. Bialek, E. F. Wieschaus, and T. Gregor, “Optimal
decoding of cellular identities in a genetic network,” Cell, vol. 176,
no. 4. Cell Press, p. 844–855.e15, 2019.
ista: Petkova MD, Tkačik G, Bialek W, Wieschaus EF, Gregor T. 2019. Optimal decoding
of cellular identities in a genetic network. Cell. 176(4), 844–855.e15.
mla: Petkova, Mariela D., et al. “Optimal Decoding of Cellular Identities in a Genetic
Network.” Cell, vol. 176, no. 4, Cell Press, 2019, p. 844–855.e15, doi:10.1016/j.cell.2019.01.007.
short: M.D. Petkova, G. Tkačik, W. Bialek, E.F. Wieschaus, T. Gregor, Cell 176 (2019)
844–855.e15.
date_created: 2019-02-10T22:59:16Z
date_published: 2019-02-07T00:00:00Z
date_updated: 2023-08-24T14:42:47Z
day: '07'
department:
- _id: GaTk
doi: 10.1016/j.cell.2019.01.007
external_id:
isi:
- '000457969200015'
pmid:
- '30712870'
intvolume: ' 176'
isi: 1
issue: '4'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1016/j.cell.2019.01.007
month: '02'
oa: 1
oa_version: Published Version
page: 844-855.e15
pmid: 1
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication: Cell
publication_status: published
publisher: Cell Press
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/cells-find-their-identity-using-a-mathematically-optimal-strategy/
scopus_import: '1'
status: public
title: Optimal decoding of cellular identities in a genetic network
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 176
year: '2019'
...
---
_id: '6046'
abstract:
- lang: eng
text: Sudden stress often triggers diverse, temporally structured gene expression
responses in microbes, but it is largely unknown how variable in time such responses
are and if genes respond in the same temporal order in every single cell. Here,
we quantified timing variability of individual promoters responding to sublethal
antibiotic stress using fluorescent reporters, microfluidics, and time‐lapse microscopy.
We identified lower and upper bounds that put definite constraints on timing variability,
which varies strongly among promoters and conditions. Timing variability can be
interpreted using results from statistical kinetics, which enable us to estimate
the number of rate‐limiting molecular steps underlying different responses. We
found that just a few critical steps control some responses while others rely
on dozens of steps. To probe connections between different stress responses, we
then tracked the temporal order and response time correlations of promoter pairs
in individual cells. Our results support that, when bacteria are exposed to the
antibiotic nitrofurantoin, the ensuing oxidative stress and SOS responses are
part of the same causal chain of molecular events. In contrast, under trimethoprim,
the acid stress response and the SOS response are part of different chains of
events running in parallel. Our approach reveals fundamental constraints on gene
expression timing and provides new insights into the molecular events that underlie
the timing of stress responses.
acknowledged_ssus:
- _id: Bio
article_number: e8470
article_processing_charge: No
author:
- first_name: Karin
full_name: Mitosch, Karin
id: 39B66846-F248-11E8-B48F-1D18A9856A87
last_name: Mitosch
- first_name: Georg
full_name: Rieckh, Georg
id: 34DA8BD6-F248-11E8-B48F-1D18A9856A87
last_name: Rieckh
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
citation:
ama: Mitosch K, Rieckh G, Bollenbach MT. Temporal order and precision of complex
stress responses in individual bacteria. Molecular systems biology. 2019;15(2).
doi:10.15252/msb.20188470
apa: Mitosch, K., Rieckh, G., & Bollenbach, M. T. (2019). Temporal order and
precision of complex stress responses in individual bacteria. Molecular Systems
Biology. Embo Press. https://doi.org/10.15252/msb.20188470
chicago: Mitosch, Karin, Georg Rieckh, and Mark Tobias Bollenbach. “Temporal Order
and Precision of Complex Stress Responses in Individual Bacteria.” Molecular
Systems Biology. Embo Press, 2019. https://doi.org/10.15252/msb.20188470.
ieee: K. Mitosch, G. Rieckh, and M. T. Bollenbach, “Temporal order and precision
of complex stress responses in individual bacteria,” Molecular systems biology,
vol. 15, no. 2. Embo Press, 2019.
ista: Mitosch K, Rieckh G, Bollenbach MT. 2019. Temporal order and precision of
complex stress responses in individual bacteria. Molecular systems biology. 15(2),
e8470.
mla: Mitosch, Karin, et al. “Temporal Order and Precision of Complex Stress Responses
in Individual Bacteria.” Molecular Systems Biology, vol. 15, no. 2, e8470,
Embo Press, 2019, doi:10.15252/msb.20188470.
short: K. Mitosch, G. Rieckh, M.T. Bollenbach, Molecular Systems Biology 15 (2019).
date_created: 2019-02-24T22:59:18Z
date_published: 2019-02-14T00:00:00Z
date_updated: 2023-08-24T14:49:53Z
day: '14'
department:
- _id: GaTk
doi: 10.15252/msb.20188470
external_id:
isi:
- '000459628300003'
pmid:
- '30765425'
intvolume: ' 15'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.ncbi.nlm.nih.gov/pubmed/30765425
month: '02'
oa: 1
oa_version: Submitted Version
pmid: 1
project:
- _id: 25E9AF9E-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P27201-B22
name: Revealing the mechanisms underlying drug interactions
- _id: 25EB3A80-B435-11E9-9278-68D0E5697425
grant_number: RGP0042/2013
name: Revealing the fundamental limits of cell growth
publication: Molecular systems biology
publication_status: published
publisher: Embo Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Temporal order and precision of complex stress responses in individual bacteria
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 15
year: '2019'
...
---
_id: '6049'
abstract:
- lang: eng
text: 'In this article it is shown that large systems with many interacting units
endowing multiple phases display self-oscillations in the presence of linear feedback
between the control and order parameters, where an Andronov–Hopf bifurcation takes
over the phase transition. This is simply illustrated through the mean field Landau
theory whose feedback dynamics turn out to be described by the Van der Pol equation
and it is then validated for the fully connected Ising model following heat bath
dynamics. Despite its simplicity, this theory accounts potentially for a rich
range of phenomena: here it is applied to describe in a stylized way (i) excess
demand-price cycles due to strong herding in a simple agent-based market model;
(ii) congestion waves in queuing networks triggered by user feedback to delays
in overloaded conditions; and (iii) metabolic network oscillations resulting from
cell growth control in a bistable phenotypic landscape.'
article_number: '045002'
article_processing_charge: Yes (in subscription journal)
author:
- first_name: Daniele
full_name: De Martino, Daniele
id: 3FF5848A-F248-11E8-B48F-1D18A9856A87
last_name: De Martino
orcid: 0000-0002-5214-4706
citation:
ama: 'De Martino D. Feedback-induced self-oscillations in large interacting systems
subjected to phase transitions. Journal of Physics A: Mathematical and Theoretical.
2019;52(4). doi:10.1088/1751-8121/aaf2dd'
apa: 'De Martino, D. (2019). Feedback-induced self-oscillations in large interacting
systems subjected to phase transitions. Journal of Physics A: Mathematical
and Theoretical. IOP Publishing. https://doi.org/10.1088/1751-8121/aaf2dd'
chicago: 'De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting
Systems Subjected to Phase Transitions.” Journal of Physics A: Mathematical
and Theoretical. IOP Publishing, 2019. https://doi.org/10.1088/1751-8121/aaf2dd.'
ieee: 'D. De Martino, “Feedback-induced self-oscillations in large interacting systems
subjected to phase transitions,” Journal of Physics A: Mathematical and Theoretical,
vol. 52, no. 4. IOP Publishing, 2019.'
ista: 'De Martino D. 2019. Feedback-induced self-oscillations in large interacting
systems subjected to phase transitions. Journal of Physics A: Mathematical and
Theoretical. 52(4), 045002.'
mla: 'De Martino, Daniele. “Feedback-Induced Self-Oscillations in Large Interacting
Systems Subjected to Phase Transitions.” Journal of Physics A: Mathematical
and Theoretical, vol. 52, no. 4, 045002, IOP Publishing, 2019, doi:10.1088/1751-8121/aaf2dd.'
short: 'D. De Martino, Journal of Physics A: Mathematical and Theoretical 52 (2019).'
date_created: 2019-02-24T22:59:19Z
date_published: 2019-01-07T00:00:00Z
date_updated: 2023-08-24T14:49:23Z
day: '07'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1088/1751-8121/aaf2dd
ec_funded: 1
external_id:
isi:
- '000455379500001'
file:
- access_level: open_access
checksum: 1112304ad363a6d8afaeccece36473cf
content_type: application/pdf
creator: kschuh
date_created: 2019-04-19T12:18:57Z
date_updated: 2020-07-14T12:47:17Z
file_id: '6344'
file_name: 2019_IOP_DeMartino.pdf
file_size: 1804557
relation: main_file
file_date_updated: 2020-07-14T12:47:17Z
has_accepted_license: '1'
intvolume: ' 52'
isi: 1
issue: '4'
language:
- iso: eng
month: '01'
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
publication: 'Journal of Physics A: Mathematical and Theoretical'
publication_status: published
publisher: IOP Publishing
quality_controlled: '1'
scopus_import: '1'
status: public
title: Feedback-induced self-oscillations in large interacting systems subjected to
phase transitions
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: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 52
year: '2019'
...
---
_id: '6071'
abstract:
- lang: eng
text: 'Transcription factors, by binding to specific sequences on the DNA, control
the precise spatio-temporal expression of genes inside a cell. However, this specificity
is limited, leading to frequent incorrect binding of transcription factors that
might have deleterious consequences on the cell. By constructing a biophysical
model of TF-DNA binding in the context of gene regulation, I will first explore
how regulatory constraints can strongly shape the distribution of a population
in sequence space. Then, by directly linking this to a picture of multiple types
of transcription factors performing their functions simultaneously inside the
cell, I will explore the extent of regulatory crosstalk -- incorrect binding interactions
between transcription factors and binding sites that lead to erroneous regulatory
states -- and understand the constraints this places on the design of regulatory
systems. I will then develop a generic theoretical framework to investigate the
coevolution of multiple transcription factors and multiple binding sites, in the
context of a gene regulatory network that performs a certain function. As a particular
tractable version of this problem, I will consider the evolution of two transcription
factors when they transmit upstream signals to downstream target genes. Specifically,
I will describe the evolutionary steady states and the evolutionary pathways involved,
along with their timescales, of a system that initially undergoes a transcription
factor duplication event. To connect this important theoretical model to the prominent
biological event of transcription factor duplication giving rise to paralogous
families, I will then describe a bioinformatics analysis of C2H2 Zn-finger transcription
factors, a major family in humans, and focus on the patterns of evolution that
paralogs have undergone in their various protein domains in the recent past. '
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Roshan
full_name: Prizak, Roshan
id: 4456104E-F248-11E8-B48F-1D18A9856A87
last_name: Prizak
citation:
ama: Prizak R. Coevolution of transcription factors and their binding sites in sequence
space. 2019. doi:10.15479/at:ista:th6071
apa: Prizak, R. (2019). Coevolution of transcription factors and their binding
sites in sequence space. Institute of Science and Technology Austria. https://doi.org/10.15479/at:ista:th6071
chicago: Prizak, Roshan. “Coevolution of Transcription Factors and Their Binding
Sites in Sequence Space.” Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/at:ista:th6071.
ieee: R. Prizak, “Coevolution of transcription factors and their binding sites in
sequence space,” Institute of Science and Technology Austria, 2019.
ista: Prizak R. 2019. Coevolution of transcription factors and their binding sites
in sequence space. Institute of Science and Technology Austria.
mla: Prizak, Roshan. Coevolution of Transcription Factors and Their Binding Sites
in Sequence Space. Institute of Science and Technology Austria, 2019, doi:10.15479/at:ista:th6071.
short: R. Prizak, Coevolution of Transcription Factors and Their Binding Sites in
Sequence Space, Institute of Science and Technology Austria, 2019.
date_created: 2019-03-06T16:16:10Z
date_published: 2019-03-11T00:00:00Z
date_updated: 2025-05-28T11:57:05Z
day: '11'
ddc:
- '576'
degree_awarded: PhD
department:
- _id: GaTk
- _id: NiBa
doi: 10.15479/at:ista:th6071
file:
- access_level: open_access
checksum: e60a72de35d270b31f1a23d50f224ec0
content_type: application/pdf
creator: rprizak
date_created: 2019-03-06T16:05:07Z
date_updated: 2020-07-14T12:47:18Z
file_id: '6072'
file_name: Thesis_final_PDFA_RoshanPrizak.pdf
file_size: 20995465
relation: main_file
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checksum: 67c2630333d05ebafef5f018863a8465
content_type: application/zip
creator: rprizak
date_created: 2019-03-06T16:09:39Z
date_updated: 2020-07-14T12:47:18Z
file_id: '6073'
file_name: thesis_v2_merge.zip
file_size: 85705272
relation: source_file
title: Latex files
file_date_updated: 2020-07-14T12:47:18Z
has_accepted_license: '1'
language:
- iso: eng
month: '03'
oa: 1
oa_version: Published Version
page: '189'
project:
- _id: 254E9036-B435-11E9-9278-68D0E5697425
call_identifier: FWF
grant_number: P28844-B27
name: Biophysics of information processing in gene regulation
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1358'
relation: part_of_dissertation
status: public
- id: '955'
relation: part_of_dissertation
status: public
status: public
supervisor:
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
title: Coevolution of transcription factors and their binding sites in sequence space
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2019'
...
---
_id: '6090'
abstract:
- lang: eng
text: Cells need to reliably sense external ligand concentrations to achieve various
biological functions such as chemotaxis or signaling. The molecular recognition
of ligands by surface receptors is degenerate in many systems, leading to crosstalk
between ligand-receptor pairs. Crosstalk is often thought of as a deviation from
optimal specific recognition, as the binding of noncognate ligands can interfere
with the detection of the receptor's cognate ligand, possibly leading to a false
triggering of a downstream signaling pathway. Here we quantify the optimal precision
of sensing the concentrations of multiple ligands by a collection of promiscuous
receptors. We demonstrate that crosstalk can improve precision in concentration
sensing and discrimination tasks. To achieve superior precision, the additional
information about ligand concentrations contained in short binding events of the
noncognate ligand should be exploited. We present a proofreading scheme to realize
an approximate estimation of multiple ligand concentrations that reaches a precision
close to the derived optimal bounds. Our results help rationalize the observed
ubiquity of receptor crosstalk in molecular sensing.
article_number: '022423'
article_processing_charge: No
author:
- first_name: Martín
full_name: Carballo-Pacheco, Martín
last_name: Carballo-Pacheco
- first_name: Jonathan
full_name: Desponds, Jonathan
last_name: Desponds
- first_name: Tatyana
full_name: Gavrilchenko, Tatyana
last_name: Gavrilchenko
- first_name: Andreas
full_name: Mayer, Andreas
last_name: Mayer
- first_name: Roshan
full_name: Prizak, Roshan
id: 4456104E-F248-11E8-B48F-1D18A9856A87
last_name: Prizak
- first_name: Gautam
full_name: Reddy, Gautam
last_name: Reddy
- first_name: Ilya
full_name: Nemenman, Ilya
last_name: Nemenman
- first_name: Thierry
full_name: Mora, Thierry
last_name: Mora
citation:
ama: Carballo-Pacheco M, Desponds J, Gavrilchenko T, et al. Receptor crosstalk improves
concentration sensing of multiple ligands. Physical Review E. 2019;99(2).
doi:10.1103/PhysRevE.99.022423
apa: Carballo-Pacheco, M., Desponds, J., Gavrilchenko, T., Mayer, A., Prizak, R.,
Reddy, G., … Mora, T. (2019). Receptor crosstalk improves concentration sensing
of multiple ligands. Physical Review E. American Physical Society. https://doi.org/10.1103/PhysRevE.99.022423
chicago: Carballo-Pacheco, Martín, Jonathan Desponds, Tatyana Gavrilchenko, Andreas
Mayer, Roshan Prizak, Gautam Reddy, Ilya Nemenman, and Thierry Mora. “Receptor
Crosstalk Improves Concentration Sensing of Multiple Ligands.” Physical Review
E. American Physical Society, 2019. https://doi.org/10.1103/PhysRevE.99.022423.
ieee: M. Carballo-Pacheco et al., “Receptor crosstalk improves concentration
sensing of multiple ligands,” Physical Review E, vol. 99, no. 2. American
Physical Society, 2019.
ista: Carballo-Pacheco M, Desponds J, Gavrilchenko T, Mayer A, Prizak R, Reddy G,
Nemenman I, Mora T. 2019. Receptor crosstalk improves concentration sensing of
multiple ligands. Physical Review E. 99(2), 022423.
mla: Carballo-Pacheco, Martín, et al. “Receptor Crosstalk Improves Concentration
Sensing of Multiple Ligands.” Physical Review E, vol. 99, no. 2, 022423,
American Physical Society, 2019, doi:10.1103/PhysRevE.99.022423.
short: M. Carballo-Pacheco, J. Desponds, T. Gavrilchenko, A. Mayer, R. Prizak, G.
Reddy, I. Nemenman, T. Mora, Physical Review E 99 (2019).
date_created: 2019-03-10T22:59:20Z
date_published: 2019-02-26T00:00:00Z
date_updated: 2024-02-28T13:12:06Z
day: '26'
department:
- _id: NiBa
- _id: GaTk
doi: 10.1103/PhysRevE.99.022423
external_id:
isi:
- '000459916500007'
intvolume: ' 99'
isi: 1
issue: '2'
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://www.biorxiv.org/content/10.1101/448118v1.abstract
month: '02'
oa: 1
oa_version: Preprint
publication: Physical Review E
publication_status: published
publisher: American Physical Society
quality_controlled: '1'
scopus_import: '1'
status: public
title: Receptor crosstalk improves concentration sensing of multiple ligands
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 99
year: '2019'
...