---
_id: '14559'
abstract:
- lang: eng
text: We consider the problem of learning control policies in discrete-time stochastic
systems which guarantee that the system stabilizes within some specified stabilization
region with probability 1. Our approach is based on the novel notion of stabilizing
ranking supermartingales (sRSMs) that we introduce in this work. Our sRSMs overcome
the limitation of methods proposed in previous works whose applicability is restricted
to systems in which the stabilizing region cannot be left once entered under any
control policy. We present a learning procedure that learns a control policy together
with an sRSM that formally certifies probability 1 stability, both learned as
neural networks. We show that this procedure can also be adapted to formally verifying
that, under a given Lipschitz continuous control policy, the stochastic system
stabilizes within some stabilizing region with probability 1. Our experimental
evaluation shows that our learning procedure can successfully learn provably stabilizing
policies in practice.
acknowledgement: This work was supported in part by the ERC-2020-AdG 101020093, ERC
CoG 863818 (FoRM-SMArt) and the European Union’s Horizon 2020 research and innovation
programme under the Marie Skłodowska-Curie Grant Agreement No. 665385.
alternative_title:
- LNCS
article_processing_charge: No
author:
- first_name: Matin
full_name: Ansaripour, Matin
last_name: Ansaripour
- first_name: Krishnendu
full_name: Chatterjee, Krishnendu
id: 2E5DCA20-F248-11E8-B48F-1D18A9856A87
last_name: Chatterjee
orcid: 0000-0002-4561-241X
- first_name: Thomas A
full_name: Henzinger, Thomas A
id: 40876CD8-F248-11E8-B48F-1D18A9856A87
last_name: Henzinger
orcid: 0000-0002-2985-7724
- first_name: Mathias
full_name: Lechner, Mathias
id: 3DC22916-F248-11E8-B48F-1D18A9856A87
last_name: Lechner
- first_name: Dorde
full_name: Zikelic, Dorde
id: 294AA7A6-F248-11E8-B48F-1D18A9856A87
last_name: Zikelic
orcid: 0000-0002-4681-1699
citation:
ama: 'Ansaripour M, Chatterjee K, Henzinger TA, Lechner M, Zikelic D. Learning provably
stabilizing neural controllers for discrete-time stochastic systems. In: 21st
International Symposium on Automated Technology for Verification and Analysis.
Vol 14215. Springer Nature; 2023:357-379. doi:10.1007/978-3-031-45329-8_17'
apa: 'Ansaripour, M., Chatterjee, K., Henzinger, T. A., Lechner, M., & Zikelic,
D. (2023). Learning provably stabilizing neural controllers for discrete-time
stochastic systems. In 21st International Symposium on Automated Technology
for Verification and Analysis (Vol. 14215, pp. 357–379). Singapore, Singapore:
Springer Nature. https://doi.org/10.1007/978-3-031-45329-8_17'
chicago: Ansaripour, Matin, Krishnendu Chatterjee, Thomas A Henzinger, Mathias Lechner,
and Dorde Zikelic. “Learning Provably Stabilizing Neural Controllers for Discrete-Time
Stochastic Systems.” In 21st International Symposium on Automated Technology
for Verification and Analysis, 14215:357–79. Springer Nature, 2023. https://doi.org/10.1007/978-3-031-45329-8_17.
ieee: M. Ansaripour, K. Chatterjee, T. A. Henzinger, M. Lechner, and D. Zikelic,
“Learning provably stabilizing neural controllers for discrete-time stochastic
systems,” in 21st International Symposium on Automated Technology for Verification
and Analysis, Singapore, Singapore, 2023, vol. 14215, pp. 357–379.
ista: 'Ansaripour M, Chatterjee K, Henzinger TA, Lechner M, Zikelic D. 2023. Learning
provably stabilizing neural controllers for discrete-time stochastic systems.
21st International Symposium on Automated Technology for Verification and Analysis.
ATVA: Automated Technology for Verification and Analysis, LNCS, vol. 14215, 357–379.'
mla: Ansaripour, Matin, et al. “Learning Provably Stabilizing Neural Controllers
for Discrete-Time Stochastic Systems.” 21st International Symposium on Automated
Technology for Verification and Analysis, vol. 14215, Springer Nature, 2023,
pp. 357–79, doi:10.1007/978-3-031-45329-8_17.
short: M. Ansaripour, K. Chatterjee, T.A. Henzinger, M. Lechner, D. Zikelic, in:,
21st International Symposium on Automated Technology for Verification and Analysis,
Springer Nature, 2023, pp. 357–379.
conference:
end_date: 2023-10-27
location: Singapore, Singapore
name: 'ATVA: Automated Technology for Verification and Analysis'
start_date: 2023-10-24
date_created: 2023-11-19T23:00:56Z
date_published: 2023-10-22T00:00:00Z
date_updated: 2023-11-20T08:30:20Z
day: '22'
department:
- _id: ToHe
- _id: KrCh
doi: 10.1007/978-3-031-45329-8_17
ec_funded: 1
intvolume: ' 14215'
language:
- iso: eng
month: '10'
oa_version: None
page: 357-379
project:
- _id: 62781420-2b32-11ec-9570-8d9b63373d4d
call_identifier: H2020
grant_number: '101020093'
name: Vigilant Algorithmic Monitoring of Software
- _id: 0599E47C-7A3F-11EA-A408-12923DDC885E
call_identifier: H2020
grant_number: '863818'
name: 'Formal Methods for Stochastic Models: Algorithms and Applications'
- _id: 2564DBCA-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '665385'
name: International IST Doctoral Program
publication: 21st International Symposium on Automated Technology for Verification
and Analysis
publication_identifier:
eissn:
- 1611-3349
isbn:
- '9783031453281'
issn:
- 0302-9743
publication_status: published
publisher: Springer Nature
quality_controlled: '1'
scopus_import: '1'
status: public
title: Learning provably stabilizing neural controllers for discrete-time stochastic
systems
type: conference
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 14215
year: '2023'
...
---
_id: '14554'
abstract:
- lang: eng
text: 'The Regularised Inertial Dean–Kawasaki model (RIDK) – introduced by the authors
and J. Zimmer in earlier works – is a nonlinear stochastic PDE capturing fluctuations
around the meanfield limit for large-scale particle systems in both particle density
and momentum density. We focus on the following two aspects. Firstly, we set up
a Discontinuous Galerkin (DG) discretisation scheme for the RIDK model: we provide
suitable definitions of numerical fluxes at the interface of the mesh elements
which are consistent with the wave-type nature of the RIDK model and grant stability
of the simulations, and we quantify the rate of convergence in mean square to
the continuous RIDK model. Secondly, we introduce modifications of the RIDK model
in order to preserve positivity of the density (such a feature only holds in a
“high-probability sense” for the original RIDK model). By means of numerical simulations,
we show that the modifications lead to physically realistic and positive density
profiles. In one case, subject to additional regularity constraints, we also prove
positivity. Finally, we present an application of our methodology to a system
of diffusing and reacting particles. Our Python code is available in open-source
format.'
acknowledgement: "The authors thank the anonymous referees for their careful reading
of the manuscript and their\r\nvaluable suggestions. FC gratefully acknowledges
funding from the Austrian Science Fund (FWF) through the project F65, and from the
European Union’s Horizon 2020 research and innovation programme under the Marie
Sk lodowska-Curie grant agreement No. 754411 (the latter funding source covered
the first part of this project)."
article_processing_charge: Yes (in subscription journal)
article_type: original
author:
- first_name: Federico
full_name: Cornalba, Federico
id: 2CEB641C-A400-11E9-A717-D712E6697425
last_name: Cornalba
orcid: 0000-0002-6269-5149
- first_name: Tony
full_name: Shardlow, Tony
last_name: Shardlow
citation:
ama: 'Cornalba F, Shardlow T. The regularised inertial Dean’ Kawasaki equation:
Discontinuous Galerkin approximation and modelling for low-density regime. ESAIM:
Mathematical Modelling and Numerical Analysis. 2023;57(5):3061-3090. doi:10.1051/m2an/2023077'
apa: 'Cornalba, F., & Shardlow, T. (2023). The regularised inertial Dean’ Kawasaki
equation: Discontinuous Galerkin approximation and modelling for low-density regime.
ESAIM: Mathematical Modelling and Numerical Analysis. EDP Sciences. https://doi.org/10.1051/m2an/2023077'
chicago: 'Cornalba, Federico, and Tony Shardlow. “The Regularised Inertial Dean’
Kawasaki Equation: Discontinuous Galerkin Approximation and Modelling for Low-Density
Regime.” ESAIM: Mathematical Modelling and Numerical Analysis. EDP Sciences,
2023. https://doi.org/10.1051/m2an/2023077.'
ieee: 'F. Cornalba and T. Shardlow, “The regularised inertial Dean’ Kawasaki equation:
Discontinuous Galerkin approximation and modelling for low-density regime,” ESAIM:
Mathematical Modelling and Numerical Analysis, vol. 57, no. 5. EDP Sciences,
pp. 3061–3090, 2023.'
ista: 'Cornalba F, Shardlow T. 2023. The regularised inertial Dean’ Kawasaki equation:
Discontinuous Galerkin approximation and modelling for low-density regime. ESAIM:
Mathematical Modelling and Numerical Analysis. 57(5), 3061–3090.'
mla: 'Cornalba, Federico, and Tony Shardlow. “The Regularised Inertial Dean’ Kawasaki
Equation: Discontinuous Galerkin Approximation and Modelling for Low-Density Regime.”
ESAIM: Mathematical Modelling and Numerical Analysis, vol. 57, no. 5, EDP
Sciences, 2023, pp. 3061–90, doi:10.1051/m2an/2023077.'
short: 'F. Cornalba, T. Shardlow, ESAIM: Mathematical Modelling and Numerical Analysis
57 (2023) 3061–3090.'
date_created: 2023-11-19T23:00:55Z
date_published: 2023-09-01T00:00:00Z
date_updated: 2023-11-20T08:38:47Z
day: '01'
ddc:
- '510'
department:
- _id: JuFi
doi: 10.1051/m2an/2023077
ec_funded: 1
file:
- access_level: open_access
checksum: 3aef1475b1882c8dec112df9a5167c39
content_type: application/pdf
creator: dernst
date_created: 2023-11-20T08:34:57Z
date_updated: 2023-11-20T08:34:57Z
file_id: '14560'
file_name: 2023_ESAIM_Cornalba.pdf
file_size: 1508534
relation: main_file
success: 1
file_date_updated: 2023-11-20T08:34:57Z
has_accepted_license: '1'
intvolume: ' 57'
issue: '5'
language:
- iso: eng
license: https://creativecommons.org/licenses/by/4.0/
month: '09'
oa: 1
oa_version: Published Version
page: 3061-3090
project:
- _id: fc31cba2-9c52-11eb-aca3-ff467d239cd2
grant_number: F6504
name: Taming Complexity in Partial Differential Systems
- _id: 260C2330-B435-11E9-9278-68D0E5697425
call_identifier: H2020
grant_number: '754411'
name: ISTplus - Postdoctoral Fellowships
publication: 'ESAIM: Mathematical Modelling and Numerical Analysis'
publication_identifier:
eissn:
- 2804-7214
issn:
- 2822-7840
publication_status: published
publisher: EDP Sciences
quality_controlled: '1'
related_material:
link:
- relation: software
url: https://github.com/tonyshardlow/RIDK-FD
scopus_import: '1'
status: public
title: 'The regularised inertial Dean'' Kawasaki equation: Discontinuous Galerkin
approximation and modelling for low-density regime'
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: 57
year: '2023'
...
---
_id: '14556'
abstract:
- lang: eng
text: Inversions are structural mutations that reverse the sequence of a chromosome
segment and reduce the effective rate of recombination in the heterozygous state.
They play a major role in adaptation, as well as in other evolutionary processes
such as speciation. Although inversions have been studied since the 1920s, they
remain difficult to investigate because the reduced recombination conferred by
them strengthens the effects of drift and hitchhiking, which in turn can obscure
signatures of selection. Nonetheless, numerous inversions have been found to be
under selection. Given recent advances in population genetic theory and empirical
study, here we review how different mechanisms of selection affect the evolution
of inversions. A key difference between inversions and other mutations, such as
single nucleotide variants, is that the fitness of an inversion may be affected
by a larger number of frequently interacting processes. This considerably complicates
the analysis of the causes underlying the evolution of inversions. We discuss
the extent to which these mechanisms can be disentangled, and by which approach.
acknowledgement: 'We are grateful to two referees and Luke Holman for valuable comments
on a previous version of our manuscript. This paper was conceived at the ESEB Progress
Meeting ‘Disentangling neutral versus adaptive evolution in chromosomal inversions’,
organized by ELB, KJ and TF and held at Tjärnö Marine Laboratory (Sweden) between
28 February and 3 March 2022. We are indebted to ESEB for sponsoring our workshop
and to the following funding bodies for supporting our research: ERC AdG 101055327
to NHB; Swedish Research Council (VR) 2018-03695 and Leverhulme Trust RPG-2021-141
to RKB; Fundação para a Ciência e a Tecnologia (FCT) contract 2020.00275.CEECIND
and research project PTDC/BIA-1232 EVL/1614/2021 to RF; Fundação para a Ciência
e a Tecnologia (FCT) junior researcher contract CEECIND/02616/2018 to IF; Swiss
National Science Foundation (SNSF) Ambizione #PZ00P3_185952 to KJG; National Science
Foundation NSF-OCE 2043905 and NSF-DEB 1655701 to KEL; Swiss National Science Foundation
(SNSF) 310030_204681 to CLP; Swedish Research Council (VR) 2021-05243 to MR; Norwegian
Research Council grant 315287 to AMW; Swiss National Science Foundation (SNSF) 31003A-182262
and FZEB-0-214654 to TF. We also thank Luca Ferretti for the discussion and Eliane
Zinn (Flatt lab) for help with reference formatting.'
article_number: '14242'
article_processing_charge: No
article_type: review
author:
- first_name: Emma L.
full_name: Berdan, Emma L.
last_name: Berdan
- first_name: Nicholas H
full_name: Barton, Nicholas H
id: 4880FE40-F248-11E8-B48F-1D18A9856A87
last_name: Barton
orcid: 0000-0002-8548-5240
- first_name: Roger
full_name: Butlin, Roger
last_name: Butlin
- first_name: Brian
full_name: Charlesworth, Brian
last_name: Charlesworth
- first_name: Rui
full_name: Faria, Rui
last_name: Faria
- first_name: Inês
full_name: Fragata, Inês
last_name: Fragata
- first_name: Kimberly J.
full_name: Gilbert, Kimberly J.
last_name: Gilbert
- first_name: Paul
full_name: Jay, Paul
last_name: Jay
- first_name: Martin
full_name: Kapun, Martin
last_name: Kapun
- first_name: Katie E.
full_name: Lotterhos, Katie E.
last_name: Lotterhos
- first_name: Claire
full_name: Mérot, Claire
last_name: Mérot
- first_name: Esra
full_name: Durmaz Mitchell, Esra
last_name: Durmaz Mitchell
- first_name: Marta
full_name: Pascual, Marta
last_name: Pascual
- first_name: Catherine L.
full_name: Peichel, Catherine L.
last_name: Peichel
- first_name: Marina
full_name: Rafajlović, Marina
last_name: Rafajlović
- first_name: Anja M
full_name: Westram, Anja M
id: 3C147470-F248-11E8-B48F-1D18A9856A87
last_name: Westram
orcid: 0000-0003-1050-4969
- first_name: Stephen W.
full_name: Schaeffer, Stephen W.
last_name: Schaeffer
- first_name: Kerstin
full_name: Johannesson, Kerstin
last_name: Johannesson
- first_name: Thomas
full_name: Flatt, Thomas
last_name: Flatt
citation:
ama: Berdan EL, Barton NH, Butlin R, et al. How chromosomal inversions reorient
the evolutionary process. Journal of Evolutionary Biology. 2023. doi:10.1111/jeb.14242
apa: Berdan, E. L., Barton, N. H., Butlin, R., Charlesworth, B., Faria, R., Fragata,
I., … Flatt, T. (2023). How chromosomal inversions reorient the evolutionary process.
Journal of Evolutionary Biology. Wiley. https://doi.org/10.1111/jeb.14242
chicago: Berdan, Emma L., Nicholas H Barton, Roger Butlin, Brian Charlesworth, Rui
Faria, Inês Fragata, Kimberly J. Gilbert, et al. “How Chromosomal Inversions Reorient
the Evolutionary Process.” Journal of Evolutionary Biology. Wiley, 2023.
https://doi.org/10.1111/jeb.14242.
ieee: E. L. Berdan et al., “How chromosomal inversions reorient the evolutionary
process,” Journal of Evolutionary Biology. Wiley, 2023.
ista: Berdan EL, Barton NH, Butlin R, Charlesworth B, Faria R, Fragata I, Gilbert
KJ, Jay P, Kapun M, Lotterhos KE, Mérot C, Durmaz Mitchell E, Pascual M, Peichel
CL, Rafajlović M, Westram AM, Schaeffer SW, Johannesson K, Flatt T. 2023. How
chromosomal inversions reorient the evolutionary process. Journal of Evolutionary
Biology., 14242.
mla: Berdan, Emma L., et al. “How Chromosomal Inversions Reorient the Evolutionary
Process.” Journal of Evolutionary Biology, 14242, Wiley, 2023, doi:10.1111/jeb.14242.
short: E.L. Berdan, N.H. Barton, R. Butlin, B. Charlesworth, R. Faria, I. Fragata,
K.J. Gilbert, P. Jay, M. Kapun, K.E. Lotterhos, C. Mérot, E. Durmaz Mitchell,
M. Pascual, C.L. Peichel, M. Rafajlović, A.M. Westram, S.W. Schaeffer, K. Johannesson,
T. Flatt, Journal of Evolutionary Biology (2023).
date_created: 2023-11-19T23:00:55Z
date_published: 2023-11-08T00:00:00Z
date_updated: 2023-11-20T08:51:09Z
day: '08'
ddc:
- '570'
department:
- _id: NiBa
doi: 10.1111/jeb.14242
has_accepted_license: '1'
language:
- iso: eng
license: https://creativecommons.org/licenses/by-nc/4.0/
main_file_link:
- open_access: '1'
url: https://doi.org/10.1111/jeb.14242
month: '11'
oa: 1
oa_version: Published Version
publication: Journal of Evolutionary Biology
publication_identifier:
eissn:
- 1420-9101
issn:
- 1010-061X
publication_status: epub_ahead
publisher: Wiley
quality_controlled: '1'
scopus_import: '1'
status: public
title: How chromosomal inversions reorient the evolutionary process
tmp:
image: /images/cc_by_nc.png
legal_code_url: https://creativecommons.org/licenses/by-nc/4.0/legalcode
name: Creative Commons Attribution-NonCommercial 4.0 International (CC BY-NC 4.0)
short: CC BY-NC (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...
---
_id: '14555'
abstract:
- lang: eng
text: The intricate regulatory processes behind actin polymerization play a crucial
role in cellular biology, including essential mechanisms such as cell migration
or cell division. However, the self-organizing principles governing actin polymerization
are still poorly understood. In this perspective article, we compare the Belousov-Zhabotinsky
(BZ) reaction, a classic and well understood chemical oscillator known for its
self-organizing spatiotemporal dynamics, with the excitable dynamics of polymerizing
actin. While the BZ reaction originates from the domain of inorganic chemistry,
it shares remarkable similarities with actin polymerization, including the characteristic
propagating waves, which are influenced by geometry and external fields, and the
emergent collective behavior. Starting with a general description of emerging
patterns, we elaborate on single droplets or cell-level dynamics, the influence
of geometric confinements and conclude with collective interactions. Comparing
these two systems sheds light on the universal nature of self-organization principles
in both living and inanimate systems.
acknowledgement: The author(s) declare that no financial support was received for
the research, authorship, and/or publication of this article.
article_number: '1287420'
article_processing_charge: Yes
article_type: original
author:
- first_name: Michael
full_name: Riedl, Michael
id: 3BE60946-F248-11E8-B48F-1D18A9856A87
last_name: Riedl
orcid: 0000-0003-4844-6311
- first_name: Michael K
full_name: Sixt, Michael K
id: 41E9FBEA-F248-11E8-B48F-1D18A9856A87
last_name: Sixt
orcid: 0000-0002-6620-9179
citation:
ama: Riedl M, Sixt MK. The excitable nature of polymerizing actin and the Belousov-Zhabotinsky
reaction. Frontiers in Cell and Developmental Biology. 2023;11. doi:10.3389/fcell.2023.1287420
apa: Riedl, M., & Sixt, M. K. (2023). The excitable nature of polymerizing actin
and the Belousov-Zhabotinsky reaction. Frontiers in Cell and Developmental
Biology. Frontiers. https://doi.org/10.3389/fcell.2023.1287420
chicago: Riedl, Michael, and Michael K Sixt. “The Excitable Nature of Polymerizing
Actin and the Belousov-Zhabotinsky Reaction.” Frontiers in Cell and Developmental
Biology. Frontiers, 2023. https://doi.org/10.3389/fcell.2023.1287420.
ieee: M. Riedl and M. K. Sixt, “The excitable nature of polymerizing actin and the
Belousov-Zhabotinsky reaction,” Frontiers in Cell and Developmental Biology,
vol. 11. Frontiers, 2023.
ista: Riedl M, Sixt MK. 2023. The excitable nature of polymerizing actin and the
Belousov-Zhabotinsky reaction. Frontiers in Cell and Developmental Biology. 11,
1287420.
mla: Riedl, Michael, and Michael K. Sixt. “The Excitable Nature of Polymerizing
Actin and the Belousov-Zhabotinsky Reaction.” Frontiers in Cell and Developmental
Biology, vol. 11, 1287420, Frontiers, 2023, doi:10.3389/fcell.2023.1287420.
short: M. Riedl, M.K. Sixt, Frontiers in Cell and Developmental Biology 11 (2023).
date_created: 2023-11-19T23:00:55Z
date_published: 2023-10-31T00:00:00Z
date_updated: 2023-11-20T08:44:17Z
day: '31'
ddc:
- '570'
department:
- _id: MiSi
doi: 10.3389/fcell.2023.1287420
file:
- access_level: open_access
checksum: 61857fc3ebf019354932e7ee684658ce
content_type: application/pdf
creator: dernst
date_created: 2023-11-20T08:41:15Z
date_updated: 2023-11-20T08:41:15Z
file_id: '14561'
file_name: 2023_FrontiersCellDevBio_Riedl.pdf
file_size: 2047622
relation: main_file
success: 1
file_date_updated: 2023-11-20T08:41:15Z
has_accepted_license: '1'
intvolume: ' 11'
language:
- iso: eng
month: '10'
oa: 1
oa_version: Published Version
publication: Frontiers in Cell and Developmental Biology
publication_identifier:
eissn:
- 2296-634X
publication_status: published
publisher: Frontiers
quality_controlled: '1'
scopus_import: '1'
status: public
title: The excitable nature of polymerizing actin and the Belousov-Zhabotinsky reaction
tmp:
image: /images/cc_by.png
legal_code_url: https://creativecommons.org/licenses/by/4.0/legalcode
name: Creative Commons Attribution 4.0 International Public License (CC-BY 4.0)
short: CC BY (4.0)
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
volume: 11
year: '2023'
...
---
_id: '14543'
abstract:
- lang: eng
text: The acyl-CoA-binding domain-containing protein 6 (ACBD6) is ubiquitously expressed,
plays a role in the acylation of lipids and proteins, and regulates the N-myristoylation
of proteins via N-myristoyltransferase enzymes (NMTs). However, its precise function
in cells is still unclear, as is the consequence of ACBD6 defects on human pathophysiology.
Utilizing exome sequencing and extensive international data sharing efforts, we
identified 45 affected individuals from 28 unrelated families (consanguinity 93%)
with bi-allelic pathogenic, predominantly loss-of-function (18/20) variants in
ACBD6. We generated zebrafish and Xenopus tropicalis acbd6 knockouts by CRISPR/Cas9
and characterized the role of ACBD6 on protein N-myristoylation with YnMyr chemical
proteomics in the model organisms and human cells, with the latter also being
subjected further to ACBD6 peroxisomal localization studies. The affected individuals
(23 males and 22 females), with ages ranging from 1 to 50 years old, typically
present with a complex and progressive disease involving moderate-to-severe global
developmental delay/intellectual disability (100%) with significant expressive
language impairment (98%), movement disorders (97%), facial dysmorphism (95%),
and mild cerebellar ataxia (85%) associated with gait impairment (94%), limb spasticity/hypertonia
(76%), oculomotor (71%) and behavioural abnormalities (65%), overweight (59%),
microcephaly (39%) and epilepsy (33%). The most conspicuous and common movement
disorder was dystonia (94%), frequently leading to early-onset progressive postural
deformities (97%), limb dystonia (55%), and cervical dystonia (31%). A jerky tremor
in the upper limbs (63%), a mild head tremor (59%), parkinsonism/hypokinesia developing
with advancing age (32%), and simple motor and vocal tics were among other frequent
movement disorders. Midline brain malformations including corpus callosum abnormalities
(70%), hypoplasia/agenesis of the anterior commissure (66%), short midbrain and
small inferior cerebellar vermis (38% each), as well as hypertrophy of the clava
(24%) were common neuroimaging findings. acbd6-deficient zebrafish and Xenopus
models effectively recapitulated many clinical phenotypes reported in patients
including movement disorders, progressive neuromotor impairment, seizures, microcephaly,
craniofacial dysmorphism, and midbrain defects accompanied by developmental delay
with increased mortality over time. Unlike ACBD5, ACBD6 did not show a peroxisomal
localisation and ACBD6-deficiency was not associated with altered peroxisomal
parameters in patient fibroblasts. Significant differences in YnMyr-labelling
were observed for 68 co- and 18 post-translationally N-myristoylated proteins
in patient-derived fibroblasts. N-Myristoylation was similarly affected in acbd6-deficient
zebrafish and Xenopus tropicalis models, including Fus, Marcks, and Chchd-related
proteins implicated in neurological diseases. The present study provides evidence
that bi-allelic pathogenic variants in ACBD6 lead to a distinct neurodevelopmental
syndrome accompanied by complex and progressive cognitive and movement disorders.
article_number: awad380
article_processing_charge: No
article_type: original
author:
- first_name: Rauan
full_name: Kaiyrzhanov, Rauan
last_name: Kaiyrzhanov
- first_name: Aboulfazl
full_name: Rad, Aboulfazl
last_name: Rad
- first_name: Sheng-Jia
full_name: Lin, Sheng-Jia
last_name: Lin
- first_name: Aida
full_name: Bertoli-Avella, Aida
last_name: Bertoli-Avella
- first_name: Wouter W
full_name: Kallemeijn, Wouter W
last_name: Kallemeijn
- first_name: Annie
full_name: Godwin, Annie
last_name: Godwin
- first_name: Maha S
full_name: Zaki, Maha S
last_name: Zaki
- first_name: Kevin
full_name: Huang, Kevin
id: 3b3d2888-1ff6-11ee-9fa6-8f209ca91fe3
last_name: Huang
orcid: 0000-0002-2512-7812
- first_name: Tracy
full_name: Lau, Tracy
last_name: Lau
- first_name: Cassidy
full_name: Petree, Cassidy
last_name: Petree
- first_name: Stephanie
full_name: Efthymiou, Stephanie
last_name: Efthymiou
- first_name: Ehsan
full_name: Ghayoor Karimiani, Ehsan
last_name: Ghayoor Karimiani
- first_name: Maja
full_name: Hempel, Maja
last_name: Hempel
- first_name: Elizabeth A
full_name: Normand, Elizabeth A
last_name: Normand
- first_name: Sabine
full_name: Rudnik-Schöneborn, Sabine
last_name: Rudnik-Schöneborn
- first_name: Ulrich A
full_name: Schatz, Ulrich A
last_name: Schatz
- first_name: Marc P
full_name: Baggelaar, Marc P
last_name: Baggelaar
- first_name: Muhammad
full_name: Ilyas, Muhammad
last_name: Ilyas
- first_name: Tipu
full_name: Sultan, Tipu
last_name: Sultan
- first_name: Javeria Raza
full_name: Alvi, Javeria Raza
last_name: Alvi
- first_name: Manizha
full_name: Ganieva, Manizha
last_name: Ganieva
- first_name: Ben
full_name: Fowler, Ben
last_name: Fowler
- first_name: Ruxandra
full_name: Aanicai, Ruxandra
last_name: Aanicai
- first_name: Gulsen
full_name: Akay Tayfun, Gulsen
last_name: Akay Tayfun
- first_name: Abdulaziz
full_name: Al Saman, Abdulaziz
last_name: Al Saman
- first_name: Abdulrahman
full_name: Alswaid, Abdulrahman
last_name: Alswaid
- first_name: Nafise
full_name: Amiri, Nafise
last_name: Amiri
- first_name: Nilufar
full_name: Asilova, Nilufar
last_name: Asilova
- first_name: Vorasuk
full_name: Shotelersuk, Vorasuk
last_name: Shotelersuk
- first_name: Patra
full_name: Yeetong, Patra
last_name: Yeetong
- first_name: Matloob
full_name: Azam, Matloob
last_name: Azam
- first_name: Meisam
full_name: Babaei, Meisam
last_name: Babaei
- first_name: Gholamreza
full_name: Bahrami Monajemi, Gholamreza
last_name: Bahrami Monajemi
- first_name: Pouria
full_name: Mohammadi, Pouria
last_name: Mohammadi
- first_name: Saeed
full_name: Samie, Saeed
last_name: Samie
- first_name: Selina Husna
full_name: Banu, Selina Husna
last_name: Banu
- first_name: Jorge Pinto
full_name: Basto, Jorge Pinto
last_name: Basto
- first_name: Fanny
full_name: Kortüm, Fanny
last_name: Kortüm
- first_name: Mislen
full_name: Bauer, Mislen
last_name: Bauer
- first_name: Peter
full_name: Bauer, Peter
last_name: Bauer
- first_name: Christian
full_name: Beetz, Christian
last_name: Beetz
- first_name: Masoud
full_name: Garshasbi, Masoud
last_name: Garshasbi
- first_name: Awatif
full_name: Hameed Issa, Awatif
last_name: Hameed Issa
- first_name: Wafaa
full_name: Eyaid, Wafaa
last_name: Eyaid
- first_name: Hind
full_name: Ahmed, Hind
last_name: Ahmed
- first_name: Narges
full_name: Hashemi, Narges
last_name: Hashemi
- first_name: Kazem
full_name: Hassanpour, Kazem
last_name: Hassanpour
- first_name: Isabella
full_name: Herman, Isabella
last_name: Herman
- first_name: Sherozjon
full_name: Ibrohimov, Sherozjon
last_name: Ibrohimov
- first_name: Ban A
full_name: Abdul-Majeed, Ban A
last_name: Abdul-Majeed
- first_name: Maria
full_name: Imdad, Maria
last_name: Imdad
- first_name: Maksudjon
full_name: Isrofilov, Maksudjon
last_name: Isrofilov
- first_name: Qassem
full_name: Kaiyal, Qassem
last_name: Kaiyal
- first_name: Suliman
full_name: Khan, Suliman
last_name: Khan
- first_name: Brian
full_name: Kirmse, Brian
last_name: Kirmse
- first_name: Janet
full_name: Koster, Janet
last_name: Koster
- first_name: Charles Marques
full_name: Lourenço, Charles Marques
last_name: Lourenço
- first_name: Tadahiro
full_name: Mitani, Tadahiro
last_name: Mitani
- first_name: Oana
full_name: Moldovan, Oana
last_name: Moldovan
- first_name: David
full_name: Murphy, David
last_name: Murphy
- first_name: Maryam
full_name: Najafi, Maryam
last_name: Najafi
- first_name: Davut
full_name: Pehlivan, Davut
last_name: Pehlivan
- first_name: Maria Eugenia
full_name: Rocha, Maria Eugenia
last_name: Rocha
- first_name: Vincenzo
full_name: Salpietro, Vincenzo
last_name: Salpietro
- first_name: Miriam
full_name: Schmidts, Miriam
last_name: Schmidts
- first_name: Adel
full_name: Shalata, Adel
last_name: Shalata
- first_name: Mohammad
full_name: Mahroum, Mohammad
last_name: Mahroum
- first_name: Jawabreh Kassem
full_name: Talbeya, Jawabreh Kassem
last_name: Talbeya
- first_name: Robert W
full_name: Taylor, Robert W
last_name: Taylor
- first_name: Dayana
full_name: Vazquez, Dayana
last_name: Vazquez
- first_name: Annalisa
full_name: Vetro, Annalisa
last_name: Vetro
- first_name: Hans R
full_name: Waterham, Hans R
last_name: Waterham
- first_name: Mashaya
full_name: Zaman, Mashaya
last_name: Zaman
- first_name: Tina A
full_name: Schrader, Tina A
last_name: Schrader
- first_name: Wendy K
full_name: Chung, Wendy K
last_name: Chung
- first_name: Renzo
full_name: Guerrini, Renzo
last_name: Guerrini
- first_name: James R
full_name: Lupski, James R
last_name: Lupski
- first_name: Joseph
full_name: Gleeson, Joseph
last_name: Gleeson
- first_name: Mohnish
full_name: Suri, Mohnish
last_name: Suri
- first_name: Yalda
full_name: Jamshidi, Yalda
last_name: Jamshidi
- first_name: Kailash P
full_name: Bhatia, Kailash P
last_name: Bhatia
- first_name: Barbara
full_name: Vona, Barbara
last_name: Vona
- first_name: Michael
full_name: Schrader, Michael
last_name: Schrader
- first_name: Mariasavina
full_name: Severino, Mariasavina
last_name: Severino
- first_name: Matthew
full_name: Guille, Matthew
last_name: Guille
- first_name: Edward W
full_name: Tate, Edward W
last_name: Tate
- first_name: Gaurav K
full_name: Varshney, Gaurav K
last_name: Varshney
- first_name: Henry
full_name: Houlden, Henry
last_name: Houlden
- first_name: Reza
full_name: Maroofian, Reza
last_name: Maroofian
citation:
ama: Kaiyrzhanov R, Rad A, Lin S-J, et al. Bi-allelic ACBD6 variants lead to a neurodevelopmental
syndrome with progressive and complex movement disorders. Brain. 2023.
doi:10.1093/brain/awad380
apa: Kaiyrzhanov, R., Rad, A., Lin, S.-J., Bertoli-Avella, A., Kallemeijn, W. W.,
Godwin, A., … Maroofian, R. (2023). Bi-allelic ACBD6 variants lead to a neurodevelopmental
syndrome with progressive and complex movement disorders. Brain. Oxford
University Press. https://doi.org/10.1093/brain/awad380
chicago: Kaiyrzhanov, Rauan, Aboulfazl Rad, Sheng-Jia Lin, Aida Bertoli-Avella,
Wouter W Kallemeijn, Annie Godwin, Maha S Zaki, et al. “Bi-Allelic ACBD6 Variants
Lead to a Neurodevelopmental Syndrome with Progressive and Complex Movement Disorders.”
Brain. Oxford University Press, 2023. https://doi.org/10.1093/brain/awad380.
ieee: R. Kaiyrzhanov et al., “Bi-allelic ACBD6 variants lead to a neurodevelopmental
syndrome with progressive and complex movement disorders,” Brain. Oxford
University Press, 2023.
ista: Kaiyrzhanov R, Rad A, Lin S-J, Bertoli-Avella A, Kallemeijn WW, Godwin A,
Zaki MS, Huang K, Lau T, Petree C, Efthymiou S, Ghayoor Karimiani E, Hempel M,
Normand EA, Rudnik-Schöneborn S, Schatz UA, Baggelaar MP, Ilyas M, Sultan T, Alvi
JR, Ganieva M, Fowler B, Aanicai R, Akay Tayfun G, Al Saman A, Alswaid A, Amiri
N, Asilova N, Shotelersuk V, Yeetong P, Azam M, Babaei M, Bahrami Monajemi G,
Mohammadi P, Samie S, Banu SH, Basto JP, Kortüm F, Bauer M, Bauer P, Beetz C,
Garshasbi M, Hameed Issa A, Eyaid W, Ahmed H, Hashemi N, Hassanpour K, Herman
I, Ibrohimov S, Abdul-Majeed BA, Imdad M, Isrofilov M, Kaiyal Q, Khan S, Kirmse
B, Koster J, Lourenço CM, Mitani T, Moldovan O, Murphy D, Najafi M, Pehlivan D,
Rocha ME, Salpietro V, Schmidts M, Shalata A, Mahroum M, Talbeya JK, Taylor RW,
Vazquez D, Vetro A, Waterham HR, Zaman M, Schrader TA, Chung WK, Guerrini R, Lupski
JR, Gleeson J, Suri M, Jamshidi Y, Bhatia KP, Vona B, Schrader M, Severino M,
Guille M, Tate EW, Varshney GK, Houlden H, Maroofian R. 2023. Bi-allelic ACBD6
variants lead to a neurodevelopmental syndrome with progressive and complex movement
disorders. Brain., awad380.
mla: Kaiyrzhanov, Rauan, et al. “Bi-Allelic ACBD6 Variants Lead to a Neurodevelopmental
Syndrome with Progressive and Complex Movement Disorders.” Brain, awad380,
Oxford University Press, 2023, doi:10.1093/brain/awad380.
short: R. Kaiyrzhanov, A. Rad, S.-J. Lin, A. Bertoli-Avella, W.W. Kallemeijn, A.
Godwin, M.S. Zaki, K. Huang, T. Lau, C. Petree, S. Efthymiou, E. Ghayoor Karimiani,
M. Hempel, E.A. Normand, S. Rudnik-Schöneborn, U.A. Schatz, M.P. Baggelaar, M.
Ilyas, T. Sultan, J.R. Alvi, M. Ganieva, B. Fowler, R. Aanicai, G. Akay Tayfun,
A. Al Saman, A. Alswaid, N. Amiri, N. Asilova, V. Shotelersuk, P. Yeetong, M.
Azam, M. Babaei, G. Bahrami Monajemi, P. Mohammadi, S. Samie, S.H. Banu, J.P.
Basto, F. Kortüm, M. Bauer, P. Bauer, C. Beetz, M. Garshasbi, A. Hameed Issa,
W. Eyaid, H. Ahmed, N. Hashemi, K. Hassanpour, I. Herman, S. Ibrohimov, B.A. Abdul-Majeed,
M. Imdad, M. Isrofilov, Q. Kaiyal, S. Khan, B. Kirmse, J. Koster, C.M. Lourenço,
T. Mitani, O. Moldovan, D. Murphy, M. Najafi, D. Pehlivan, M.E. Rocha, V. Salpietro,
M. Schmidts, A. Shalata, M. Mahroum, J.K. Talbeya, R.W. Taylor, D. Vazquez, A.
Vetro, H.R. Waterham, M. Zaman, T.A. Schrader, W.K. Chung, R. Guerrini, J.R. Lupski,
J. Gleeson, M. Suri, Y. Jamshidi, K.P. Bhatia, B. Vona, M. Schrader, M. Severino,
M. Guille, E.W. Tate, G.K. Varshney, H. Houlden, R. Maroofian, Brain (2023).
date_created: 2023-11-16T12:36:51Z
date_published: 2023-11-10T00:00:00Z
date_updated: 2023-11-20T10:17:32Z
day: '10'
department:
- _id: GradSch
doi: 10.1093/brain/awad380
extern: '1'
keyword:
- Neurology (clinical)
language:
- iso: eng
main_file_link:
- open_access: '1'
url: https://doi.org/10.1093/brain/awad380
month: '11'
oa: 1
oa_version: Submitted Version
publication: Brain
publication_identifier:
eissn:
- 1460-2156
issn:
- 0006-8950
publication_status: epub_ahead
publisher: Oxford University Press
quality_controlled: '1'
scopus_import: '1'
status: public
title: Bi-allelic ACBD6 variants lead to a neurodevelopmental syndrome with progressive
and complex movement disorders
type: journal_article
user_id: 2DF688A6-F248-11E8-B48F-1D18A9856A87
year: '2023'
...