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Article ; Online: μMatch

James Klatzow / Giovanni Dalmasso / Neus Martínez-Abadías / James Sharpe / Virginie Uhlmann

Frontiers in Computer Science, Vol

3D Shape Correspondence for Biological Image Data

2022 Volume 4

Abstract: Modern microscopy technologies allow imaging biological objects in 3D over a wide range of spatial and temporal scales, opening the way for a quantitative assessment of morphology. However, establishing a correspondence between objects to be compared, a ... ...

Abstract	Modern microscopy technologies allow imaging biological objects in 3D over a wide range of spatial and temporal scales, opening the way for a quantitative assessment of morphology. However, establishing a correspondence between objects to be compared, a first necessary step of most shape analysis workflows, remains challenging for soft-tissue objects without striking features allowing them to be landmarked. To address this issue, we introduce the μMatch 3D shape correspondence pipeline. μMatch implements a state-of-the-art correspondence algorithm initially developed for computer graphics and packages it in a streamlined pipeline including tools to carry out all steps from input data pre-processing to classical shape analysis routines. Importantly, μMatch does not require any landmarks on the object surface and establishes correspondence in a fully automated manner. Our open-source method is implemented in Python and can be used to process collections of objects described as triangular meshes. We quantitatively assess the validity of μMatch relying on a well-known benchmark dataset and further demonstrate its reliability by reproducing published results previously obtained through manual landmarking.
Keywords	bioimage analysis ; shape quantification ; correspondence ; alignment ; computational morphometry ; Electronic computers. Computer science ; QA75.5-76.95
Subject code	004
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Periodic formation of epithelial somites from human pluripotent stem cells

Marina Sanaki-Matsumiya / Mitsuhiro Matsuda / Nicola Gritti / Fumio Nakaki / James Sharpe / Vikas Trivedi / Miki Ebisuya

Nature Communications, Vol 13, Iss 1, Pp 1-

2022 Volume 14

Abstract: Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic ... ...

Abstract	Somitogenesis has been well characterized in model organisms, resulting in detailed description of the somite segmentation clock. Here they generate somitogenic organoids from human pluripotent stem cells that recapitulate somitogenesis, periodic segmentation, and proper polarity.
Keywords	Science ; Q
Language	English
Publishing date	2022-04-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: A spectrum of modularity in multi‐functional gene circuits

Alba Jiménez / James Cotterell / Andreea Munteanu / James Sharpe

Molecular Systems Biology, Vol 13, Iss 4, Pp n/a-n/a (2017)

2017

Abstract: Abstract A major challenge in systems biology is to understand the relationship between a circuit's structure and its function, but how is this relationship affected if the circuit must perform multiple distinct functions within the same organism? In ... ...

Abstract	Abstract A major challenge in systems biology is to understand the relationship between a circuit's structure and its function, but how is this relationship affected if the circuit must perform multiple distinct functions within the same organism? In particular, to what extent do multi‐functional circuits contain modules which reflect the different functions? Here, we computationally survey a range of bi‐functional circuits which show no simple structural modularity: They can switch between two qualitatively distinct functions, while both functions depend on all genes of the circuit. Our analysis reveals two distinct classes: hybrid circuits which overlay two simpler mono‐functional sub‐circuits within their circuitry, and emergent circuits, which do not. In this second class, the bi‐functionality emerges from more complex designs which are not fully decomposable into distinct modules and are consequently less intuitive to predict or understand. These non‐intuitive emergent circuits are just as robust as their hybrid counterparts, and we therefore suggest that the common bias toward studying modular systems may hinder our understanding of real biological circuits.
Keywords	decomposability ; dynamical mechanism ; gene circuits ; modularity ; multi‐functionality ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
Subject code	000
Language	English
Publishing date	2017-04-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Mechanistic explanations for restricted evolutionary paths that emerge from gene regulatory networks.

James Cotterell / James Sharpe

PLoS ONE, Vol 8, Iss 4, p e

2013 Volume 61178

Abstract: The extent and the nature of the constraints to evolutionary trajectories are central issues in biology. Constraints can be the result of systems dynamics causing a non-linear mapping between genotype and phenotype. How prevalent are these developmental ... ...

Abstract	The extent and the nature of the constraints to evolutionary trajectories are central issues in biology. Constraints can be the result of systems dynamics causing a non-linear mapping between genotype and phenotype. How prevalent are these developmental constraints and what is their mechanistic basis? Although this has been extensively explored at the level of epistatic interactions between nucleotides within a gene, or amino acids within a protein, selection acts at the level of the whole organism, and therefore epistasis between disparate genes in the genome is expected due to their functional interactions within gene regulatory networks (GRNs) which are responsible for many aspects of organismal phenotype. Here we explore epistasis within GRNs capable of performing a common developmental function--converting a continuous morphogen input into discrete spatial domains. By exploring the full complement of GRN wiring designs that are able to perform this function, we analyzed all possible mutational routes between functional GRNs. Through this study we demonstrate that mechanistic constraints are common for GRNs that perform even a simple function. We demonstrate a common mechanistic cause for such a constraint involving complementation between counter-balanced gene-gene interactions. Furthermore we show how such constraints can be bypassed by means of "permissive" mutations that buffer changes in a direct route between two GRN topologies that would normally be unviable. We show that such bypasses are common and thus we suggest that unlike what was observed in protein sequence-function relationships, the "tape of life" is less reproducible when one considers higher levels of biological organization.
Keywords	Medicine ; R ; Science ; Q
Subject code	612
Language	English
Publishing date	2013-01-01T00:00:00Z
Publisher	Public Library of Science (PLoS)
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: High-throughput mathematical analysis identifies Turing networks for patterning with equally diffusing signals

Luciano Marcon / Xavier Diego / James Sharpe / Patrick Müller

eLife, Vol

2016 Volume 5

Abstract: The Turing reaction-diffusion model explains how identical cells can self-organize to form spatial patterns. It has been suggested that extracellular signaling molecules with different diffusion coefficients underlie this model, but the contribution of ... ...

Abstract	The Turing reaction-diffusion model explains how identical cells can self-organize to form spatial patterns. It has been suggested that extracellular signaling molecules with different diffusion coefficients underlie this model, but the contribution of cell-autonomous signaling components is largely unknown. We developed an automated mathematical analysis to derive a catalog of realistic Turing networks. This analysis reveals that in the presence of cell-autonomous factors, networks can form a pattern with equally diffusing signals and even for any combination of diffusion coefficients. We provide a software (available at http://www.RDNets.com) to explore these networks and to constrain topologies with qualitative and quantitative experimental data. We use the software to examine the self-organizing networks that control embryonic axis specification and digit patterning. Finally, we demonstrate how existing synthetic circuits can be extended with additional feedbacks to form Turing reaction-diffusion systems. Our study offers a new theoretical framework to understand multicellular pattern formation and enables the wide-spread use of mathematical biology to engineer synthetic patterning systems.
Keywords	pattern formation ; self-organization ; diffusion-driven instability ; Turing patterns ; differential diffusivity ; Medicine ; R ; Science ; Q ; Biology (General) ; QH301-705.5
Language	English
Publishing date	2016-04-01T00:00:00Z
Publisher	eLife Sciences Publications Ltd
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Multimodal in vivo Imaging of the Integrated Postnatal Development of Brain and Skull and Its Co-modulation With Neurodevelopment in a Down Syndrome Mouse Model

Sergi Llambrich / Rubèn González / Julia Albaigès / Jens Wouters / Fopke Marain / Uwe Himmelreich / James Sharpe / Mara Dierssen / Willy Gsell / Neus Martínez-Abadías / Greetje Vande Velde

Frontiers in Medicine, Vol

2022 Volume 9

Abstract: The brain and skeletal systems are intimately integrated during development through common molecular pathways. This is evidenced by genetic disorders where brain and skull dysmorphologies are associated. However, the mechanisms underlying neural and ... ...

Abstract	The brain and skeletal systems are intimately integrated during development through common molecular pathways. This is evidenced by genetic disorders where brain and skull dysmorphologies are associated. However, the mechanisms underlying neural and skeletal interactions are poorly understood. Using the Ts65Dn mouse model of Down syndrome (DS) as a case example, we performed the first longitudinal assessment of brain, skull and neurobehavioral development to determine alterations in the coordinated morphogenesis of brain and skull. We optimized a multimodal protocol combining in vivo micro-computed tomography (μCT) and magnetic resonance imaging (μMRI) with morphometric analyses and neurodevelopmental tests to longitudinally monitor the different systems' development trajectories during the first postnatal weeks. We also explored the impact of a perinatal treatment with green tea extracts enriched in epigallocatechin-3-gallate (GTE-EGCG), which can modulate cognition, brain and craniofacial development in DS. Our analyses quantified alterations associated with DS, with skull dysmorphologies appearing before brain anomalies, reduced integration and delayed acquisition of neurodevelopmental traits. Perinatal GTE-EGCG induced disparate effects and disrupted the magnitude of integration and covariation patterns between brain and skull. Our results exemplify how a longitudinal research approach evaluating the development of multiple systems can reveal the effect of morphological integration modulating the response of pathological phenotypes to treatment, furthering our understanding of complex genetic disorders.
Keywords	development ; brain and skull integration ; down syndrome ; GTE-EGCG ; μCT imaging ; μMRI ; Medicine (General) ; R5-920
Subject code	616
Language	English
Publishing date	2022-02-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: ViceCT and whiceCT for simultaneous high-resolution visualization of craniofacial, brain and ventricular anatomy from micro-computed tomography

Sergi Llambrich / Jens Wouters / Uwe Himmelreich / Mara Dierssen / James Sharpe / Willy Gsell / Neus Martínez-Abadías / Greetje Vande Velde

Scientific Reports, Vol 10, Iss 1, Pp 1-

2020 Volume 17

Abstract: Abstract Up to 40% of congenital diseases present disturbances of brain and craniofacial development resulting in simultaneous alterations of both systems. Currently, the best available method to preclinically visualize the brain and the bones ... ...

Abstract	Abstract Up to 40% of congenital diseases present disturbances of brain and craniofacial development resulting in simultaneous alterations of both systems. Currently, the best available method to preclinically visualize the brain and the bones simultaneously is to co-register micro-magnetic resonance (µMR) and micro-computed tomography (µCT) scans of the same specimen. However, this requires expertise and access to both imaging techniques, dedicated software and post-processing knowhow. To provide a more affordable, reliable and accessible alternative, recent research has focused on optimizing a contrast-enhanced µCT protocol using iodine as contrast agent that delivers brain and bone images from a single scan. However, the available methods still cannot provide the complete visualization of both the brain and whole craniofacial complex. In this study, we have established an optimized protocol to diffuse the contrast into the brain that allows visualizing the brain parenchyma and the complete craniofacial structure in a single ex vivo µCT scan (whiceCT). In addition, we have developed a new technique that allows visualizing the brain ventricles using a bilateral stereotactic injection of iodine-based contrast (viceCT). Finally, we have tested both techniques in a mouse model of Down syndrome, as it is a neurodevelopmental disorder with craniofacial, brain and ventricle defects. The combined use of viceCT and whiceCT provides a complete visualization of the brain and bones with intact craniofacial structure of an adult mouse ex vivo using a single imaging modality.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2020-10-01T00:00:00Z
Publisher	Nature Publishing Group
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: The fin-to-limb transition as the re-organization of a Turing pattern

Koh Onimaru / Luciano Marcon / Marco Musy / Mikiko Tanaka / James Sharpe

Nature Communications, Vol 7, Iss 1, Pp 1-

2016 Volume 9

Abstract: Mouse digit patterning is controlled by a Turing network of Bmp, Sox9, and Wnt. Here, Onimaru et al. show that fin patterning in the catshark, Scyliorhinus canicula, is controlled by the same network with a different spatial organization; thus, the ... ...

Abstract	Mouse digit patterning is controlled by a Turing network of Bmp, Sox9, and Wnt. Here, Onimaru et al. show that fin patterning in the catshark, Scyliorhinus canicula, is controlled by the same network with a different spatial organization; thus, the Turing network is deeply conserved in limb development.
Keywords	Science ; Q
Language	English
Publishing date	2016-05-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: An atlas of gene regulatory networks reveals multiple three‐gene mechanisms for interpreting morphogen gradients

James Cotterell / James Sharpe

Molecular Systems Biology, Vol 6, Iss 1, Pp n/a-n/a (2010)

2010

Abstract: The interpretation of morphogen gradients is a pivotal concept in developmental biology, and several mechanisms have been proposed to explain how gene regulatory networks (GRNs) achieve concentration‐dependent responses. However, the number of different ... ...

Abstract	The interpretation of morphogen gradients is a pivotal concept in developmental biology, and several mechanisms have been proposed to explain how gene regulatory networks (GRNs) achieve concentration‐dependent responses. However, the number of different mechanisms that may exist for cells to interpret morphogens, and the importance of design features such as feedback or local cell–cell communication, is unclear. A complete understanding of such systems will require going beyond a case‐by‐case analysis of real morphogen interpretation mechanisms and mapping out a complete GRN ‘design space.’ Here, we generate a first atlas of design space for GRNs capable of patterning a homogeneous field of cells into discrete gene expression domains by interpreting a fixed morphogen gradient. We uncover multiple very distinct mechanisms distributed discretely across the atlas, thereby expanding the repertoire of morphogen interpretation network motifs. Analyzing this diverse collection of mechanisms also allows us to predict that local cell–cell communication will rarely be responsible for the basic dose‐dependent response of morphogen interpretation networks.
Keywords	design space ; gene network ; morphogen ; patterning ; systems biology ; Biology (General) ; QH301-705.5 ; Medicine (General) ; R5-920
Subject code	004
Language	English
Publishing date	2010-01-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Green tea extracts containing epigallocatechin-3-gallate modulate facial development in Down syndrome

John M. Starbuck / Sergi Llambrich / Rubèn Gonzàlez / Julia Albaigès / Anna Sarlé / Jens Wouters / Alejandro González / Xavier Sevillano / James Sharpe / Rafael De La Torre / Mara Dierssen / Greetje Vande Velde / Neus Martínez-Abadías

Scientific Reports, Vol 11, Iss 1, Pp 1-

2021 Volume 13

Abstract: Abstract Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, ... ...

Abstract	Abstract Trisomy of human chromosome 21 (Down syndrome, DS) alters development of multiple organ systems, including the face and underlying skeleton. Besides causing stigmata, these facial dysmorphologies can impair vital functions such as hearing, breathing, mastication, and health. To investigate the therapeutic potential of green tea extracts containing epigallocatechin-3-gallate (GTE-EGCG) for alleviating facial dysmorphologies associated with DS, we performed an experimental study with continued pre- and postnatal treatment with two doses of GTE-EGCG supplementation in a mouse model of DS, and an observational study of children with DS whose parents administered EGCG as a green tea supplement. We evaluated the effect of high (100 mg/kg/day) or low doses (30 mg/kg/day) of GTE-EGCG, administered from embryonic day 9 to post-natal day 29, on the facial skeletal development in the Ts65Dn mouse model. In a cross-sectional observational study, we assessed the facial shape in DS and evaluated the effects of self-medication with green tea extracts in children from 0 to 18 years old. The main outcomes are 3D quantitative morphometric measures of the face, acquired either with micro-computed tomography (animal study) or photogrammetry (human study). The lowest experimentally tested GTE-EGCG dose improved the facial skeleton morphology in a mouse model of DS. In humans, GTE-EGCG supplementation was associated with reduced facial dysmorphology in children with DS when treatment was administered during the first 3 years of life. However, higher GTE-EGCG dosing disrupted normal development and increased facial dysmorphology in both trisomic and euploid mice. We conclude that GTE-EGCG modulates facial development with dose-dependent effects. Considering the potentially detrimental effects observed in mice, the therapeutic relevance of controlled GTE-EGCG administration towards reducing facial dysmorphology in young children with Down syndrome has yet to be confirmed by clinical studies.
Keywords	Medicine ; R ; Science ; Q
Subject code	616
Language	English
Publishing date	2021-02-01T00:00:00Z
Publisher	Nature Portfolio
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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