A unified design space of synthetic stripe-forming networks.
Ontology highlight
ABSTRACT:
SUBMITTER: Schaerli Y
PROVIDER: S-EPMC4172969 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Interpreting a morphogen gradient into a single stripe of gene-expression is a fundamental unit of patterning in early embryogenesis. From both experimental data and computational studies the feed-forward motifs stand out as minimal networks capable of this patterning function. Positive feedback within gene networks has been hypothesised to enhance the sharpness and precision of gene-expression borders, however a systematic analysis has not yet been reported. Here we set out to assess this hypothesis, and find an unexpected result. The addition of positive-feedback can have different effects on two different designs of feed-forward motif- it increases the parametric robustness of one design, while being neutral or detrimental to the other. These results shed light on the abundance of the former motif and especially of mutual-inhibition positive feedback in developmental networks.
| S-EPMC4023129 | biostudies-literature
Project description:MotivationSynthetic biology studies how to design and construct biological systems with functions that do not exist in nature. Biochemical networks, although easier to control, have been used less frequently than genetic networks as a base to build a synthetic system. To date, no clear engineering principles exist to design such cell-free biochemical networks.ResultsWe describe a methodology for the construction of synthetic biochemical networks based on three main steps: design, simulation and experimental validation. We developed BioNetCAD to help users to go through these steps. BioNetCAD allows designing abstract networks that can be implemented thanks to CompuBioTicDB, a database of parts for synthetic biology. BioNetCAD enables also simulations with the HSim software and the classical Ordinary Differential Equations (ODE). We demonstrate with a case study that BioNetCAD can rationalize and reduce further experimental validation during the construction of a biochemical network.Availability and implementationBioNetCAD is freely available at http://www.sysdiag.cnrs.fr/BioNetCAD. It is implemented in Java and supported on MS Windows. CompuBioTicDB is freely accessible at http://compubiotic.sysdiag.cnrs.fr/.
| S-EPMC2935418 | biostudies-literature
Project description:Predicting the dynamics and functions of microbiomes constructed from the bottom-up is a key challenge in exploiting them to our benefit. Current models based on ecological theory fail to capture complex community behaviors due to higher order interactions, do not scale well with increasing complexity and in considering multiple functions. We develop and apply a long short-term memory (LSTM) framework to advance our understanding of community assembly and health-relevant metabolite production using a synthetic human gut community. A mainstay of recurrent neural networks, the LSTM learns a high dimensional data-driven non-linear dynamical system model. We show that the LSTM model can outperform the widely used generalized Lotka-Volterra model based on ecological theory. We build methods to decipher microbe-microbe and microbe-metabolite interactions from an otherwise black-box model. These methods highlight that Actinobacteria, Firmicutes and Proteobacteria are significant drivers of metabolite production whereas Bacteroides shape community dynamics. We use the LSTM model to navigate a large multidimensional functional landscape to design communities with unique health-relevant metabolite profiles and temporal behaviors. In sum, the accuracy of the LSTM model can be exploited for experimental planning and to guide the design of synthetic microbiomes with target dynamic functions.
| S-EPMC9225007 | biostudies-literature
Project description:Paralleling the increasing availability of protein-protein interaction (PPI) network data, several network alignment methods have been proposed. Network alignments have been used to uncover functionally conserved network parts and to transfer annotations. However, due to the computational intractability of the network alignment problem, aligners are heuristics providing divergent solutions and no consensus exists on a gold standard, or which scoring scheme should be used to evaluate them. We comprehensively evaluate the alignment scoring schemes and global network aligners on large scale PPI data and observe that three methods, HUBALIGN, L-GRAAL and NATALIE, regularly produce the most topologically and biologically coherent alignments. We study the collective behaviour of network aligners and observe that PPI networks are almost entirely aligned with a handful of aligners that we unify into a new tool, Ulign. Ulign enables complete alignment of two networks, which traditional global and local aligners fail to do. Also, multiple mappings of Ulign define biologically relevant soft clusterings of proteins in PPI networks, which may be used for refining the transfer of annotations across networks. Hence, PPI networks are already well investigated by current aligners, so to gain additional biological insights, a paradigm shift is needed. We propose such a shift come from aligning all available data types collectively rather than any particular data type in isolation from others.
| S-EPMC5430463 | biostudies-literature
Project description:Transcriptional enhancers act as docking stations for combinations of transcription factors and thereby regulate spatiotemporal activation of their target genes. A single enhancer, of a few hundred base pairs in length, can autonomously and independently of its location and orientation drive cell-type specific expression of a gene or transgene. It has been a long-standing goal in the field to decode the regulatory logic of an enhancer and to understand the details of how spatiotemporal gene expression is encoded in an enhancer sequence. Recently, deep learning models have yielded unprecedented insight into the enhancer code, and well-trained models are reaching a level of understanding that may be close to complete. As a consequence, we hypothesized that deep learning models can be used to guide the directed design of synthetic, cell type specific enhancers, and that this process would allow for a detailed tracing of all enhancer features at nucleotide-level resolution. Here we implemented and compared three different design strategies, each built on a deep learning model: (1) directed sequence evolution; (2) directed iterative motif implanting; and (3) generative design. We evaluated the function of fully synthetic enhancers to specifically target Kenyon cells or glial cells in the fruit fly brain using transgenic animals. We then exploited this concept further by creating “dual-code” enhancers that target two cell types, and minimal enhancers smaller than 50 base pairs that are fully functional. By examining the trajectories followed during state space searches towards functional enhancers, we could accurately define the enhancer code as the optimal strength, combination, and relative distance of TF activator motifs, and the absence of TF repressor motifs. Finally, we applied the same three strategies to successfully design human enhancers, finding highly similar design principles as in Drosophila. In conclusion, enhancer design guided by deep learning leads to better understanding of how enhancers work and shows that their code can be exploited to manipulate cell states.
2023-11-19 | GSE240003 | GEO
Project description:PurposeComplementary information obtained from multiple contrasts of tissue facilitates physicians assessing, diagnosing and planning treatment of a variety of diseases. However, acquiring multiple contrasts magnetic resonance images (MRI) for every patient using multiple pulse sequences is time-consuming and expensive, where, medical image synthesis has been demonstrated as an effective alternative. The purpose of this study is to develop a unified framework for multimodal MR image synthesis.MethodsA unified generative adversarial network consisting of only a single generator and a single discriminator was developed to learn the mappings among images of four different modalities. The generator took an image and its modality label as inputs and learned to synthesize the image in the target modality, while the discriminator was trained to distinguish between real and synthesized images and classify them to their corresponding modalities. The network was trained and tested using multimodal brain MRI consisting of four different contrasts which are T1-weighted (T1), T1-weighted and contrast-enhanced (T1c), T2-weighted (T2), and fluid-attenuated inversion recovery (Flair). Quantitative assessments of our proposed method were made through computing normalized mean absolute error (NMAE), peak signal-to-noise ratio (PSNR), structural similarity index measurement (SSIM), visual information fidelity (VIF), and naturalness image quality evaluator (NIQE).ResultsThe proposed model was trained and tested on a cohort of 274 glioma patients with well-aligned multi-types of MRI scans. After the model was trained, tests were conducted by using each of T1, T1c, T2, Flair as a single input modality to generate its respective rest modalities. Our proposed method shows high accuracy and robustness for image synthesis with arbitrary MRI modality that is available in the database as input. For example, with T1 as input modality, the NMAEs for the generated T1c, T2, Flair respectively are 0.034 ± 0.005, 0.041 ± 0.006, and 0.041 ± 0.006, the PSNRs respectively are 32.353 ± 2.525 dB, 30.016 ± 2.577 dB, and 29.091 ± 2.795 dB, the SSIMs are 0.974 ± 0.059, 0.969 ± 0.059, and 0.959 ± 0.059, the VIF are 0.750 ± 0.087, 0.706 ± 0.097, and 0.654 ± 0.062, and NIQE are 1.396 ± 0.401, 1.511 ± 0.460, and 1.259 ± 0.358, respectively.ConclusionsWe proposed a novel multimodal MR image synthesis method based on a unified generative adversarial network. The network takes an image and its modality label as inputs and synthesizes multimodal images in a single forward pass. The results demonstrate that the proposed method is able to accurately synthesize multimodal MR images from a single MR image.
| S-EPMC7796974 | biostudies-literature
Project description:The shape transformation of some biological systems inspires scientists to create sophisticated structures at the nano- and macro- scales. However, to be useful in engineering, the mechanics of governing such a spontaneous, parallel and large deformation must be well understood. In this study, a kirigami approach is used to fold a bilayer planar sheet featuring a specific pattern into a buckliball under a certain thermal stimulus. Importantly, this prescribed spherical object can retract into a much smaller sphere due to constructive buckling caused by radially inward displacement. By minimizing the potential strain energy, we obtain a critical temperature, below which the patterned sheet exhibits identical principal curvatures everywhere in the self-folding procedure and above which buckling occurs. The applicability of the theoretical analysis to the self-folding of sheets with a diversity of patterns is verified by the finite element method.
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Project description:Multicellular entities are characterized by intricate spatial patterns, intimately related to the functions they perform. These patterns are often created from isotropic embryonic structures, without external information cues guiding the symmetry breaking process. Mature biological structures also display characteristic scales with repeating distributions of signals or chemical species across space. Many candidate patterning modules have been used to explain processes during development and typically include a set of interacting and diffusing chemicals or agents known as morphogens. Great effort has been put forward to better understand the conditions in which pattern-forming processes can occur in the biological domain. However, evidence and practical knowledge allowing us to engineer symmetry-breaking is still lacking. Here we follow a different approach by designing a synthetic gene circuit in E. coli that implements a local activation long-range inhibition mechanism. The synthetic gene network implements an artificial differentiation process that changes the physicochemical properties of the agents. Using both experimental results and modeling, we show that the proposed system is capable of symmetry-breaking leading to regular spatial patterns during colony growth. Studying how these patterns emerge is fundamental to further our understanding of the evolution of biocomplexity and the role played by self-organization. The artificial system studied here and the engineering perspective on embryogenic processes can help validate developmental theories and identify universal properties underpinning biological pattern formation, with special interest for the area of synthetic developmental biology.
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Project description:The hypothesis of a general psychopathology factor (p factor) has been advanced in recent years. It is an innovation with breakthrough potential, in the perspective of a unified view of psychopathology; however, what remains a controversial topic is how its nature might be conceptualized. The current paper outlines a semiotic, embodied and psychoanalytic conceptualization of psychopathology - the Phase Space of Meaning (PSM) model - aimed at providing ontological grounds to the p factor hypothesis. Framed within a more general model of how the mind works, the PSM model maintains that the p factor can be conceived as the empirical marker of the degree of rigidity of the meaning-maker's way of interpreting experience, namely of the dimensions of meanings used to map the environment's variability. As to the clinical implications, two main aspects are outlined. First, according PSM model, psychopathology is not an invariant condition, and does not have a set dimensionality, but is able to vary it locally, in order to address the requirement of situated action. Second, psychopathology is conceived as one of the mind's modes of working, rather than the manifestation of its disruption. Finally, the puzzling issue of the interplay between stability and variability in the evolutionary trajectories of patients along with their life events is addressed and discussed.
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Project description:Deep models trained in supervised mode have achieved remarkable success on a variety of tasks. When labeled samples are limited, self-supervised learning (SSL) is emerging as a new paradigm for making use of large amounts of unlabeled samples. SSL has achieved promising performance on natural language and image learning tasks. Recently, there is a trend to extend such success to graph data using graph neural networks (GNNs). In this survey, we provide a unified review of different ways of training GNNs using SSL. Specifically, we categorize SSL methods into contrastive and predictive models. In either category, we provide a unified framework for methods as well as how these methods differ in each component under the framework. Our unified treatment of SSL methods for GNNs sheds light on the similarities and differences of various methods, setting the stage for developing new methods and algorithms. We also summarize different SSL settings and the corresponding datasets used in each setting. To facilitate methodological development and empirical comparison, we develop a standardized testbed for SSL in GNNs, including implementations of common baseline methods, datasets, and evaluation metrics.
| S-EPMC9902037 | biostudies-literature