---
_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:
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creator: scepeda
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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'
...