---
_id: '8657'
abstract:
- lang: eng
text: "Synthesis of proteins – translation – is a fundamental process of life. Quantitative
studies anchor translation into the context of bacterial physiology and reveal
several mathematical relationships, called “growth laws,” which capture physiological
feedbacks between protein synthesis and cell growth. Growth laws describe the
dependency of the ribosome abundance as a function of growth rate, which can change
depending on the growth conditions. Perturbations of translation reveal that bacteria
employ a compensatory strategy in which the reduced translation capability results
in increased expression of the translation machinery.\r\nPerturbations of translation
are achieved in various ways; clinically interesting is the application of translation-targeting
antibiotics – translation inhibitors. The antibiotic effects on bacterial physiology
are often poorly understood. Bacterial responses to two or more simultaneously
applied antibiotics are even more puzzling. The combined antibiotic effect determines
the type of drug interaction, which ranges from synergy (the effect is stronger
than expected) to antagonism (the effect is weaker) and suppression (one of the
drugs loses its potency).\r\nIn the first part of this work, we systematically
measure the pairwise interaction network for translation inhibitors that interfere
with different steps in translation. We find that the interactions are surprisingly
diverse and tend to be more antagonistic. To explore the underlying mechanisms,
we begin with a minimal biophysical model of combined antibiotic action. We base
this model on the kinetics of antibiotic uptake and binding together with the
physiological response described by the growth laws. The biophysical model explains
some drug interactions, but not all; it specifically fails to predict suppression.\r\nIn
the second part of this work, we hypothesize that elusive suppressive drug interactions
result from the interplay between ribosomes halted in different stages of translation.
To elucidate this putative mechanism of drug interactions between translation
inhibitors, we generate translation bottlenecks genetically using in- ducible
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 partially causes
these interactions.\r\nWe extend this approach by varying two translation bottlenecks
simultaneously. This approach reveals the suppression of translocation inhibition
by inhibited translation. We rationalize this effect by modeling dense traffic
of ribosomes that move on transcripts in a translation factor-mediated manner.
This model predicts a dissolution of traffic jams caused by inhibited translocation
when the density of ribosome traffic is reduced by lowered initiation. We base
this model on the growth laws and quantitative relationships between different
translation and growth parameters.\r\nIn the final part of this work, we describe
a set of tools aimed at quantification of physiological and translation parameters.
We further develop a simple model that directly connects the abundance of a translation
factor with the growth rate, which allows us to extract physiological parameters
describing initiation. We demonstrate the development of tools for measuring translation
rate.\r\nThis thesis showcases how a combination of high-throughput growth rate
mea- surements, genetics, and modeling can reveal mechanisms of drug interactions.
Furthermore, by a gradual transition from combinations of antibiotics to precise
genetic interventions, we demonstrated the equivalency between genetic and chemi-
cal perturbations of translation. These findings tile the path for quantitative
studies of antibiotic combinations and illustrate future approaches towards the
quantitative description of translation."
acknowledged_ssus:
- _id: LifeSc
- _id: M-Shop
acknowledgement: I thank Life Science Facilities for their continuous support with
providing top-notch laboratory materials, keeping the devices humming, and coordinating
the repairs and building of custom-designed laboratory equipment with the MIBA Machine
shop.
alternative_title:
- ISTA Thesis
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. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. 2020. doi:10.15479/AT:ISTA:8657'
apa: 'Kavcic, B. (2020). Perturbations of protein synthesis: from antibiotics
to genetics and physiology. Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:8657'
chicago: 'Kavcic, Bor. “Perturbations of Protein Synthesis: From Antibiotics to
Genetics and Physiology.” Institute of Science and Technology Austria, 2020. https://doi.org/10.15479/AT:ISTA:8657.'
ieee: 'B. Kavcic, “Perturbations of protein synthesis: from antibiotics to genetics
and physiology,” Institute of Science and Technology Austria, 2020.'
ista: 'Kavcic B. 2020. Perturbations of protein synthesis: from antibiotics to genetics
and physiology. Institute of Science and Technology Austria.'
mla: 'Kavcic, Bor. Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology. Institute of Science and Technology Austria, 2020, doi:10.15479/AT:ISTA:8657.'
short: 'B. Kavcic, Perturbations of Protein Synthesis: From Antibiotics to Genetics
and Physiology, Institute of Science and Technology Austria, 2020.'
date_created: 2020-10-13T16:46:14Z
date_published: 2020-10-14T00:00:00Z
date_updated: 2023-09-07T13:20:48Z
day: '14'
ddc:
- '571'
- '530'
- '570'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:8657
file:
- access_level: open_access
checksum: d708ecd62b6fcc3bc1feb483b8dbe9eb
content_type: application/pdf
creator: bkavcic
date_created: 2020-10-15T06:41:20Z
date_updated: 2021-10-07T22:30:03Z
embargo: 2021-10-06
file_id: '8663'
file_name: kavcicB_thesis202009.pdf
file_size: 52636162
relation: main_file
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checksum: bb35f2352a04db19164da609f00501f3
content_type: application/zip
creator: bkavcic
date_created: 2020-10-15T06:41:53Z
date_updated: 2021-10-07T22:30:03Z
embargo_to: open_access
file_id: '8664'
file_name: 2020b.zip
file_size: 321681247
relation: source_file
file_date_updated: 2021-10-07T22:30:03Z
has_accepted_license: '1'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
page: '271'
publication_identifier:
isbn:
- 978-3-99078-011-4
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '7673'
relation: part_of_dissertation
status: public
- id: '8250'
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
- first_name: Mark Tobias
full_name: Bollenbach, Mark Tobias
id: 3E6DB97A-F248-11E8-B48F-1D18A9856A87
last_name: Bollenbach
orcid: 0000-0003-4398-476X
title: 'Perturbations of protein synthesis: from antibiotics to genetics and physiology'
type: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
year: '2020'
...
---
_id: '8250'
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.'
acknowledgement: "We thank M. Hennessey-Wesen, I. Tomanek, K. Jain, A. Staron, K.
Tomasek, M. Scott,\r\nK.C. Huang, and Z. Gitai for reading the manuscript and constructive
comments. B.K. is\r\nindebted to C. Guet for additional guidance and generous support,
which rendered this\r\nwork possible. B.K. thanks all members of Guet group for
many helpful discussions and\r\nsharing of resources. B.K. additionally acknowledges
the tremendous support from A.\r\nAngermayr and K. Mitosch with experimental work.
We further thank E. Brown for\r\nhelpful comments regarding lamotrigine, and A.
Buskirk for valuable suggestions\r\nregarding the ribosome footprint size. This
work was supported in part by Austrian\r\nScience Fund (FWF) standalone grants P
27201-B22 (to T.B.) and P 28844 (to G.T.),\r\nHFSP program Grant RGP0042/2013 (to
T.B.), German Research Foundation (DFG)\r\nstandalone grant BO 3502/2-1 (to T.B.),
and German Research Foundation (DFG)\r\nCollaborative Research Centre (SFB) 1310
(to T.B.). Open access funding provided by\r\nProjekt DEAL."
article_number: '4013'
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: 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. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 2020;11. doi:10.1038/s41467-020-17734-z
apa: Kavcic, B., Tkačik, G., & Bollenbach, M. T. (2020). Mechanisms of drug
interactions between translation-inhibiting antibiotics. Nature Communications.
Springer Nature. https://doi.org/10.1038/s41467-020-17734-z
chicago: Kavcic, Bor, Gašper Tkačik, and Mark Tobias Bollenbach. “Mechanisms of
Drug Interactions between Translation-Inhibiting Antibiotics.” Nature Communications.
Springer Nature, 2020. https://doi.org/10.1038/s41467-020-17734-z.
ieee: B. Kavcic, G. Tkačik, and M. T. Bollenbach, “Mechanisms of drug interactions
between translation-inhibiting antibiotics,” Nature Communications, vol.
11. Springer Nature, 2020.
ista: Kavcic B, Tkačik G, Bollenbach MT. 2020. Mechanisms of drug interactions between
translation-inhibiting antibiotics. Nature Communications. 11, 4013.
mla: Kavcic, Bor, et al. “Mechanisms of Drug Interactions between Translation-Inhibiting
Antibiotics.” Nature Communications, vol. 11, 4013, Springer Nature, 2020,
doi:10.1038/s41467-020-17734-z.
short: B. Kavcic, G. Tkačik, M.T. Bollenbach, Nature Communications 11 (2020).
date_created: 2020-08-12T09:13:50Z
date_published: 2020-08-11T00:00:00Z
date_updated: 2024-03-28T23:30:08Z
day: '11'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1038/s41467-020-17734-z
external_id:
isi:
- '000562769300008'
file:
- access_level: open_access
checksum: 986bebb308850a55850028d3d2b5b664
content_type: application/pdf
creator: dernst
date_created: 2020-08-17T07:36:57Z
date_updated: 2020-08-17T07:36:57Z
file_id: '8275'
file_name: 2020_NatureComm_Kavcic.pdf
file_size: 1965672
relation: main_file
success: 1
file_date_updated: 2020-08-17T07:36:57Z
has_accepted_license: '1'
intvolume: ' 11'
isi: 1
language:
- iso: eng
month: '08'
oa: 1
oa_version: Published Version
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: Nature Communications
publication_identifier:
issn:
- 2041-1723
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
record:
- id: '8657'
relation: dissertation_contains
status: public
status: public
title: 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: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 11
year: '2020'
...
---
_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: 2024-03-28T23:30:08Z
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: '7652'
abstract:
- lang: eng
text: Organisms cope with change by taking advantage of transcriptional regulators.
However, when faced with rare environments, the evolution of transcriptional regulators
and their promoters may be too slow. Here, we investigate whether the intrinsic
instability of gene duplication and amplification provides a generic alternative
to canonical gene regulation. Using real-time monitoring of gene-copy-number mutations
in Escherichia coli, we show that gene duplications and amplifications enable
adaptation to fluctuating environments by rapidly generating copy-number and,
therefore, expression-level polymorphisms. This amplification-mediated gene expression
tuning (AMGET) occurs on timescales that are similar to canonical gene regulation
and can respond to rapid environmental changes. Mathematical modelling shows that
amplifications also tune gene expression in stochastic environments in which transcription-factor-based
schemes are hard to evolve or maintain. The fleeting nature of gene amplifications
gives rise to a generic population-level mechanism that relies on genetic heterogeneity
to rapidly tune the expression of any gene, without leaving any genomic signature.
acknowledgement: We thank L. Hurst, N. Barton, M. Pleska, M. Steinrück, B. Kavcic
and A. Staron for input on the manuscript, and To. Bergmiller and R. Chait for help
with microfluidics experiments. I.T. is a recipient the OMV fellowship. R.G. is
a recipient of a DOC (Doctoral Fellowship Programme of the Austrian Academy of Sciences)
Fellowship of the Austrian Academy of Sciences.
article_processing_charge: No
article_type: original
author:
- first_name: Isabella
full_name: Tomanek, Isabella
id: 3981F020-F248-11E8-B48F-1D18A9856A87
last_name: Tomanek
orcid: 0000-0001-6197-363X
- first_name: Rok
full_name: Grah, Rok
id: 483E70DE-F248-11E8-B48F-1D18A9856A87
last_name: Grah
orcid: 0000-0003-2539-3560
- first_name: M.
full_name: Lagator, M.
last_name: Lagator
- first_name: A. M. C.
full_name: Andersson, A. M. C.
last_name: Andersson
- first_name: Jonathan P
full_name: Bollback, Jonathan P
id: 2C6FA9CC-F248-11E8-B48F-1D18A9856A87
last_name: Bollback
orcid: 0000-0002-4624-4612
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
- 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: Tomanek I, Grah R, Lagator M, et al. Gene amplification as a form of population-level
gene expression regulation. Nature Ecology & Evolution. 2020;4(4):612-625.
doi:10.1038/s41559-020-1132-7
apa: Tomanek, I., Grah, R., Lagator, M., Andersson, A. M. C., Bollback, J. P., Tkačik,
G., & Guet, C. C. (2020). Gene amplification as a form of population-level
gene expression regulation. Nature Ecology & Evolution. Springer Nature.
https://doi.org/10.1038/s41559-020-1132-7
chicago: Tomanek, Isabella, Rok Grah, M. Lagator, A. M. C. Andersson, Jonathan P
Bollback, Gašper Tkačik, and Calin C Guet. “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Nature Ecology & Evolution. Springer Nature,
2020. https://doi.org/10.1038/s41559-020-1132-7.
ieee: I. Tomanek et al., “Gene amplification as a form of population-level
gene expression regulation,” Nature Ecology & Evolution, vol. 4, no.
4. Springer Nature, pp. 612–625, 2020.
ista: Tomanek I, Grah R, Lagator M, Andersson AMC, Bollback JP, Tkačik G, Guet CC.
2020. Gene amplification as a form of population-level gene expression regulation.
Nature Ecology & Evolution. 4(4), 612–625.
mla: Tomanek, Isabella, et al. “Gene Amplification as a Form of Population-Level
Gene Expression Regulation.” Nature Ecology & Evolution, vol. 4, no.
4, Springer Nature, 2020, pp. 612–25, doi:10.1038/s41559-020-1132-7.
short: I. Tomanek, R. Grah, M. Lagator, A.M.C. Andersson, J.P. Bollback, G. Tkačik,
C.C. Guet, Nature Ecology & Evolution 4 (2020) 612–625.
date_created: 2020-04-08T15:20:53Z
date_published: 2020-04-01T00:00:00Z
date_updated: 2024-03-28T23:30:37Z
day: '01'
ddc:
- '570'
department:
- _id: GaTk
- _id: CaGu
doi: 10.1038/s41559-020-1132-7
external_id:
isi:
- '000519008300005'
file:
- access_level: open_access
checksum: ef3bbf42023e30b2c24a6278025d2040
content_type: application/pdf
creator: dernst
date_created: 2020-10-09T09:56:01Z
date_updated: 2020-10-09T09:56:01Z
file_id: '8640'
file_name: 2020_NatureEcolEvo_Tomanek.pdf
file_size: 745242
relation: main_file
success: 1
file_date_updated: 2020-10-09T09:56:01Z
has_accepted_license: '1'
intvolume: ' 4'
isi: 1
issue: '4'
language:
- iso: eng
month: '04'
oa: 1
oa_version: Submitted Version
page: 612-625
project:
- _id: 267C84F4-B435-11E9-9278-68D0E5697425
name: Biophysically realistic genotype-phenotype maps for regulatory networks
publication: Nature Ecology & Evolution
publication_identifier:
issn:
- 2397-334X
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
related_material:
link:
- description: News on IST Homepage
relation: press_release
url: https://ist.ac.at/en/news/how-to-thrive-without-gene-regulation/
record:
- id: '8155'
relation: dissertation_contains
status: public
- id: '7383'
relation: research_data
status: public
- id: '7016'
relation: research_data
status: public
- id: '8653'
relation: used_in_publication
status: public
scopus_import: '1'
status: public
title: Gene amplification as a form of population-level gene expression regulation
type: journal_article
user_id: 4359f0d1-fa6c-11eb-b949-802e58b17ae8
volume: 4
year: '2020'
...
---
_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
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: '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: '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: '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: '6784'
abstract:
- lang: eng
text: Mathematical models have been used successfully at diverse scales of biological
organization, ranging from ecology and population dynamics to stochastic reaction
events occurring between individual molecules in single cells. Generally, many
biological processes unfold across multiple scales, with mutations being the best
studied example of how stochasticity at the molecular scale can influence outcomes
at the population scale. In many other contexts, however, an analogous link between
micro- and macro-scale remains elusive, primarily due to the challenges involved
in setting up and analyzing multi-scale models. Here, we employ such a model to
investigate how stochasticity propagates from individual biochemical reaction
events in the bacterial innate immune system to the ecology of bacteria and bacterial
viruses. We show analytically how the dynamics of bacterial populations are shaped
by the activities of immunity-conferring enzymes in single cells and how the ecological
consequences imply optimal bacterial defense strategies against viruses. Our results
suggest that bacterial populations in the presence of viruses can either optimize
their initial growth rate or their population size, with the first strategy favoring
simple immunity featuring a single restriction modification system and the second
strategy favoring complex bacterial innate immunity featuring several simultaneously
active restriction modification systems.
article_number: e1007168
article_processing_charge: No
article_type: original
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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
citation:
ama: Ruess J, Pleska M, Guet CC, Tkačik G. Molecular noise of innate immunity shapes
bacteria-phage ecologies. PLoS Computational Biology. 2019;15(7). doi:10.1371/journal.pcbi.1007168
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Molecular noise
of innate immunity shapes bacteria-phage ecologies. PLoS Computational Biology.
Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Molecular
Noise of Innate Immunity Shapes Bacteria-Phage Ecologies.” PLoS Computational
Biology. Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Molecular noise of innate
immunity shapes bacteria-phage ecologies,” PLoS Computational Biology,
vol. 15, no. 7. Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Molecular noise of innate immunity
shapes bacteria-phage ecologies. PLoS Computational Biology. 15(7), e1007168.
mla: Ruess, Jakob, et al. “Molecular Noise of Innate Immunity Shapes Bacteria-Phage
Ecologies.” PLoS Computational Biology, vol. 15, no. 7, e1007168, Public
Library of Science, 2019, doi:10.1371/journal.pcbi.1007168.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, PLoS Computational Biology 15
(2019).
date_created: 2019-08-11T21:59:19Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2023-08-29T07:10:06Z
day: '02'
ddc:
- '570'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168
external_id:
isi:
- '000481577700032'
file:
- access_level: open_access
checksum: 7ded4721b41c2a0fc66a1c634540416a
content_type: application/pdf
creator: dernst
date_created: 2019-08-12T12:27:26Z
date_updated: 2020-07-14T12:47:40Z
file_id: '6803'
file_name: 2019_PlosComputBiology_Ruess.pdf
file_size: 2200003
relation: main_file
file_date_updated: 2020-07-14T12:47:40Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '7'
language:
- iso: eng
month: '07'
oa: 1
oa_version: Published Version
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
- _id: 251BCBEC-B435-11E9-9278-68D0E5697425
grant_number: RGY0079/2011
name: Multi-Level Conflicts in Evolutionary Dynamics of Restriction-Modification
Systems
publication: PLoS Computational Biology
publication_identifier:
eissn:
- 1553-7358
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '9786'
relation: research_data
status: public
scopus_import: '1'
status: public
title: Molecular noise of innate immunity shapes bacteria-phage ecologies
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: 15
year: '2019'
...
---
_id: '9786'
article_processing_charge: No
author:
- first_name: Jakob
full_name: Ruess, Jakob
id: 4A245D00-F248-11E8-B48F-1D18A9856A87
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Maros
full_name: Pleska, Maros
id: 4569785E-F248-11E8-B48F-1D18A9856A87
last_name: Pleska
orcid: 0000-0001-7460-7479
- 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
citation:
ama: Ruess J, Pleska M, Guet CC, Tkačik G. Supporting text and results. 2019. doi:10.1371/journal.pcbi.1007168.s001
apa: Ruess, J., Pleska, M., Guet, C. C., & Tkačik, G. (2019). Supporting text
and results. Public Library of Science. https://doi.org/10.1371/journal.pcbi.1007168.s001
chicago: Ruess, Jakob, Maros Pleska, Calin C Guet, and Gašper Tkačik. “Supporting
Text and Results.” Public Library of Science, 2019. https://doi.org/10.1371/journal.pcbi.1007168.s001.
ieee: J. Ruess, M. Pleska, C. C. Guet, and G. Tkačik, “Supporting text and results.”
Public Library of Science, 2019.
ista: Ruess J, Pleska M, Guet CC, Tkačik G. 2019. Supporting text and results, Public
Library of Science, 10.1371/journal.pcbi.1007168.s001.
mla: Ruess, Jakob, et al. Supporting Text and Results. Public Library of
Science, 2019, doi:10.1371/journal.pcbi.1007168.s001.
short: J. Ruess, M. Pleska, C.C. Guet, G. Tkačik, (2019).
date_created: 2021-08-06T08:23:43Z
date_published: 2019-07-02T00:00:00Z
date_updated: 2023-08-29T07:10:05Z
day: '02'
department:
- _id: CaGu
- _id: GaTk
doi: 10.1371/journal.pcbi.1007168.s001
month: '07'
oa_version: Published Version
publisher: Public Library of Science
related_material:
record:
- id: '6784'
relation: used_in_publication
status: public
status: public
title: Supporting text and results
type: research_data_reference
user_id: 6785fbc1-c503-11eb-8a32-93094b40e1cf
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
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: '6900'
abstract:
- lang: eng
text: Across diverse biological systems—ranging from neural networks to intracellular
signaling and genetic regulatory networks—the information about changes in the
environment is frequently encoded in the full temporal dynamics of the network
nodes. A pressing data-analysis challenge has thus been to efficiently estimate
the amount of information that these dynamics convey from experimental data. Here
we develop and evaluate decoding-based estimation methods to lower bound the mutual
information about a finite set of inputs, encoded in single-cell high-dimensional
time series data. For biological reaction networks governed by the chemical Master
equation, we derive model-based information approximations and analytical upper
bounds, against which we benchmark our proposed model-free decoding estimators.
In contrast to the frequently-used k-nearest-neighbor estimator, decoding-based
estimators robustly extract a large fraction of the available information from
high-dimensional trajectories with a realistic number of data samples. We apply
these estimators to previously published data on Erk and Ca2+ signaling in mammalian
cells and to yeast stress-response, and find that substantial amount of information
about environmental state can be encoded by non-trivial response statistics even
in stationary signals. We argue that these single-cell, decoding-based information
estimates, rather than the commonly-used tests for significant differences between
selected population response statistics, provide a proper and unbiased measure
for the performance of biological signaling networks.
article_processing_charge: No
author:
- first_name: Sarah A
full_name: Cepeda Humerez, Sarah A
id: 3DEE19A4-F248-11E8-B48F-1D18A9856A87
last_name: Cepeda Humerez
- first_name: Jakob
full_name: Ruess, Jakob
last_name: Ruess
orcid: 0000-0003-1615-3282
- first_name: Gašper
full_name: Tkačik, Gašper
id: 3D494DCA-F248-11E8-B48F-1D18A9856A87
last_name: Tkačik
orcid: 0000-0002-6699-1455
citation:
ama: Cepeda Humerez SA, Ruess J, Tkačik G. Estimating information in time-varying
signals. PLoS computational biology. 2019;15(9):e1007290. doi:10.1371/journal.pcbi.1007290
apa: Cepeda Humerez, S. A., Ruess, J., & Tkačik, G. (2019). Estimating information
in time-varying signals. PLoS Computational Biology. Public Library of
Science. https://doi.org/10.1371/journal.pcbi.1007290
chicago: Cepeda Humerez, Sarah A, Jakob Ruess, and Gašper Tkačik. “Estimating Information
in Time-Varying Signals.” PLoS Computational Biology. Public Library of
Science, 2019. https://doi.org/10.1371/journal.pcbi.1007290.
ieee: S. A. Cepeda Humerez, J. Ruess, and G. Tkačik, “Estimating information in
time-varying signals,” PLoS computational biology, vol. 15, no. 9. Public
Library of Science, p. e1007290, 2019.
ista: Cepeda Humerez SA, Ruess J, Tkačik G. 2019. Estimating information in time-varying
signals. PLoS computational biology. 15(9), e1007290.
mla: Cepeda Humerez, Sarah A., et al. “Estimating Information in Time-Varying Signals.”
PLoS Computational Biology, vol. 15, no. 9, Public Library of Science,
2019, p. e1007290, doi:10.1371/journal.pcbi.1007290.
short: S.A. Cepeda Humerez, J. Ruess, G. Tkačik, PLoS Computational Biology 15 (2019)
e1007290.
date_created: 2019-09-22T22:00:37Z
date_published: 2019-09-03T00:00:00Z
date_updated: 2023-09-07T12:55:21Z
day: '03'
ddc:
- '570'
department:
- _id: GaTk
doi: 10.1371/journal.pcbi.1007290
external_id:
isi:
- '000489741800021'
pmid:
- '31479447'
file:
- access_level: open_access
checksum: 81bdce1361c9aa8395d6fa635fb6ab47
content_type: application/pdf
creator: kschuh
date_created: 2019-10-01T10:53:45Z
date_updated: 2020-07-14T12:47:44Z
file_id: '6925'
file_name: 2019_PLoS_Cepeda-Humerez.pdf
file_size: 3081855
relation: main_file
file_date_updated: 2020-07-14T12:47:44Z
has_accepted_license: '1'
intvolume: ' 15'
isi: 1
issue: '9'
language:
- iso: eng
month: '09'
oa: 1
oa_version: Published Version
page: e1007290
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: PLoS computational biology
publication_identifier:
eissn:
- '15537358'
publication_status: published
publisher: Public Library of Science
quality_controlled: '1'
related_material:
record:
- id: '6473'
relation: part_of_dissertation
status: public
scopus_import: '1'
status: public
title: Estimating information in time-varying signals
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: 15
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
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: '6473'
abstract:
- lang: eng
text: "Single cells are constantly interacting with their environment and each other,
more importantly, the accurate perception of environmental cues is crucial for
growth, survival, and reproduction. This communication between cells and their
environment can be formalized in mathematical terms and be quantified as the information
flow between them, as prescribed by information theory. \r\nThe recent availability
of real–time dynamical patterns of signaling molecules in single cells has allowed
us to identify encoding about the identity of the environment in the time–series.
However, efficient estimation of the information transmitted by these signals
has been a data–analysis challenge due to the high dimensionality of the trajectories
and the limited number of samples. In the first part of this thesis, we develop
and evaluate decoding–based estimation methods to lower bound the mutual information
and derive model–based precise information estimates for biological reaction networks
governed by the chemical master equation. This is followed by applying the decoding-based
methods to study the intracellular representation of extracellular changes in
budding yeast, by observing the transient dynamics of nuclear translocation of
10 transcription factors in response to 3 stress conditions. Additionally, we
apply these estimators to previously published data on ERK and Ca2+ signaling
and yeast stress response. We argue that this single cell decoding-based measure
of information provides an unbiased, quantitative and interpretable measure for
the fidelity of biological signaling processes. \r\nFinally, in the last section,
we deal with gene regulation which is primarily controlled by transcription factors
(TFs) that bind to the DNA to activate gene expression. The possibility that non-cognate
TFs activate transcription diminishes the accuracy of regulation with potentially
disastrous effects for the cell. This ’crosstalk’ acts as a previously unexplored
source of noise in biochemical networks and puts a strong constraint on their
performance. To mitigate erroneous initiation we propose an out of equilibrium
scheme that implements kinetic proofreading. We show that such architectures are
favored over their equilibrium counterparts for complex organisms despite introducing
noise in gene expression. "
alternative_title:
- ISTA Thesis
article_processing_charge: No
author:
- first_name: Sarah A
full_name: Cepeda Humerez, Sarah A
id: 3DEE19A4-F248-11E8-B48F-1D18A9856A87
last_name: Cepeda Humerez
citation:
ama: Cepeda Humerez SA. Estimating information flow in single cells. 2019. doi:10.15479/AT:ISTA:6473
apa: Cepeda Humerez, S. A. (2019). Estimating information flow in single cells.
Institute of Science and Technology Austria. https://doi.org/10.15479/AT:ISTA:6473
chicago: Cepeda Humerez, Sarah A. “Estimating Information Flow in Single Cells.”
Institute of Science and Technology Austria, 2019. https://doi.org/10.15479/AT:ISTA:6473.
ieee: S. A. Cepeda Humerez, “Estimating information flow in single cells,” Institute
of Science and Technology Austria, 2019.
ista: Cepeda Humerez SA. 2019. Estimating information flow in single cells. Institute
of Science and Technology Austria.
mla: Cepeda Humerez, Sarah A. Estimating Information Flow in Single Cells.
Institute of Science and Technology Austria, 2019, doi:10.15479/AT:ISTA:6473.
short: S.A. Cepeda Humerez, Estimating Information Flow in Single Cells, Institute
of Science and Technology Austria, 2019.
date_created: 2019-05-21T00:11:23Z
date_published: 2019-05-23T00:00:00Z
date_updated: 2023-09-19T15:13:26Z
day: '23'
ddc:
- '004'
degree_awarded: PhD
department:
- _id: GaTk
doi: 10.15479/AT:ISTA:6473
file:
- access_level: closed
checksum: 75f9184c1346e10a5de5f9cc7338309a
content_type: application/zip
creator: scepeda
date_created: 2019-05-23T11:18:16Z
date_updated: 2020-07-14T12:47:31Z
file_id: '6480'
file_name: Thesis_Cepeda.zip
file_size: 23937464
relation: source_file
- access_level: open_access
checksum: afdc0633ddbd71d5b13550d7fb4f4454
content_type: application/pdf
creator: scepeda
date_created: 2019-05-23T11:18:13Z
date_updated: 2020-07-14T12:47:31Z
file_id: '6481'
file_name: CepedaThesis.pdf
file_size: 16646985
relation: main_file
file_date_updated: 2020-07-14T12:47:31Z
has_accepted_license: '1'
keyword:
- Information estimation
- Time-series
- data analysis
language:
- iso: eng
month: '05'
oa: 1
oa_version: Published Version
page: '135'
publication_identifier:
issn:
- 2663-337X
publication_status: published
publisher: Institute of Science and Technology Austria
related_material:
record:
- id: '1576'
relation: dissertation_contains
status: public
- id: '6900'
relation: dissertation_contains
status: public
- id: '281'
relation: dissertation_contains
status: public
- id: '2016'
relation: dissertation_contains
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: Estimating information flow in single cells
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: dissertation
user_id: c635000d-4b10-11ee-a964-aac5a93f6ac1
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: 2023-09-22T10:00:48Z
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
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file_name: Thesis_final_PDFA_RoshanPrizak.pdf
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creator: rprizak
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date_updated: 2020-07-14T12:47:18Z
file_id: '6073'
file_name: thesis_v2_merge.zip
file_size: 85705272
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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: '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: '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'
...
---
_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
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: 2024-03-06T14:22:51Z
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: '306'
abstract:
- lang: eng
text: A cornerstone of statistical inference, the maximum entropy framework is being
increasingly applied to construct descriptive and predictive models of biological
systems, especially complex biological networks, from large experimental data
sets. Both its broad applicability and the success it obtained in different contexts
hinge upon its conceptual simplicity and mathematical soundness. Here we try to
concisely review the basic elements of the maximum entropy principle, starting
from the notion of ‘entropy’, and describe its usefulness for the analysis of
biological systems. As examples, we focus specifically on the problem of reconstructing
gene interaction networks from expression data and on recent work attempting to
expand our system-level understanding of bacterial metabolism. Finally, we highlight
some extensions and potential limitations of the maximum entropy approach, and
point to more recent developments that are likely to play a key role in the upcoming
challenges of extracting structures and information from increasingly rich, high-throughput
biological data.
article_number: e00596
author:
- first_name: Andrea
full_name: De Martino, Andrea
last_name: De Martino
- 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 A, De Martino D. An introduction to the maximum entropy approach
and its application to inference problems in biology. Heliyon. 2018;4(4).
doi:10.1016/j.heliyon.2018.e00596
apa: De Martino, A., & De Martino, D. (2018). An introduction to the maximum
entropy approach and its application to inference problems in biology. Heliyon.
Elsevier. https://doi.org/10.1016/j.heliyon.2018.e00596
chicago: De Martino, Andrea, and Daniele De Martino. “An Introduction to the Maximum
Entropy Approach and Its Application to Inference Problems in Biology.” Heliyon.
Elsevier, 2018. https://doi.org/10.1016/j.heliyon.2018.e00596.
ieee: A. De Martino and D. De Martino, “An introduction to the maximum entropy approach
and its application to inference problems in biology,” Heliyon, vol. 4,
no. 4. Elsevier, 2018.
ista: De Martino A, De Martino D. 2018. An introduction to the maximum entropy approach
and its application to inference problems in biology. Heliyon. 4(4), e00596.
mla: De Martino, Andrea, and Daniele De Martino. “An Introduction to the Maximum
Entropy Approach and Its Application to Inference Problems in Biology.” Heliyon,
vol. 4, no. 4, e00596, Elsevier, 2018, doi:10.1016/j.heliyon.2018.e00596.
short: A. De Martino, D. De Martino, Heliyon 4 (2018).
date_created: 2018-12-11T11:45:44Z
date_published: 2018-04-01T00:00:00Z
date_updated: 2021-01-12T07:40:46Z
day: '01'
ddc:
- '530'
department:
- _id: GaTk
doi: 10.1016/j.heliyon.2018.e00596
ec_funded: 1
file:
- access_level: open_access
checksum: 67010cf5e3b3e0637c659371714a715a
content_type: application/pdf
creator: dernst
date_created: 2019-02-06T07:36:24Z
date_updated: 2020-07-14T12:45:59Z
file_id: '5929'
file_name: 2018_Heliyon_DeMartino.pdf
file_size: 994490
relation: main_file
file_date_updated: 2020-07-14T12:45:59Z
has_accepted_license: '1'
intvolume: ' 4'
issue: '4'
language:
- iso: eng
month: '04'
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: Heliyon
publication_status: published
publisher: Elsevier
quality_controlled: '1'
scopus_import: 1
status: public
title: An introduction to the maximum entropy approach and its application to inference
problems in biology
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: 4
year: '2018'
...