scholarly journals Generating Ampicillin-Level Antimicrobial Peptides with Activity-Aware Generative Adversarial Networks

Author(s):  
Andrejs Tucs ◽  
Duy Phuoc Tran ◽  
Akiko Yumoto ◽  
Yoshihiro Ito ◽  
Takanori Uzawa ◽  
...  

<p>Antimicrobial peptides are a potential solution to the threat of multidrug-resistant bacterial pathogens. Recently, deep generative models including generative adversarial networks (GANs) have been shown to be capable of designing new antimicrobial peptides. Intuitively, a GAN controls the probability distribution of generated sequences to cover active peptides as much as possible. This paper presents a peptide-specialized model called PepGAN that takes the balance between covering active peptides and</p><p>dodging non-active peptides. As a result, PepGAN has superior statistical fidelity with respect to physicochemical descriptors including charge, hydrophobicity and weight. Top six peptides were synthesized and one of them was confirmed to be highly antimicrobial. The minimum inhibitory concentration was 3.1μg/mL, indicating that the peptide is twice as strong as ampicillin.</p>

2020 ◽  
Author(s):  
Andrejs Tucs ◽  
Duy Phuoc Tran ◽  
Akiko Yumoto ◽  
Yoshihiro Ito ◽  
Takanori Uzawa ◽  
...  

<p>Antimicrobial peptides are a potential solution to the threat of multidrug-resistant bacterial pathogens. Recently, deep generative models including generative adversarial networks (GANs) have been shown to be capable of designing new antimicrobial peptides. Intuitively, a GAN controls the probability distribution of generated sequences to cover active peptides as much as possible. This paper presents a peptide-specialized model called PepGAN that takes the balance between covering active peptides and</p><p>dodging non-active peptides. As a result, PepGAN has superior statistical fidelity with respect to physicochemical descriptors including charge, hydrophobicity and weight. Top six peptides were synthesized and one of them was confirmed to be highly antimicrobial. The minimum inhibitory concentration was 3.1μg/mL, indicating that the peptide is twice as strong as ampicillin.</p>


2020 ◽  
Vol 20 (14) ◽  
pp. 1264-1273 ◽  
Author(s):  
Bruno Casciaro ◽  
Floriana Cappiello ◽  
Walter Verrusio ◽  
Mauro Cacciafesta ◽  
Maria Luisa Mangoni

The frequent occurrence of multidrug-resistant strains to conventional antimicrobials has led to a clear decline in antibiotic therapies. Therefore, new molecules with different mechanisms of action are extremely necessary. Due to their unique properties, antimicrobial peptides (AMPs) represent a valid alternative to conventional antibiotics and many of them have been characterized for their activity and cytotoxicity. However, the effects that these peptides cause at concentrations below the minimum growth inhibitory concentration (MIC) have yet to be fully analyzed along with the underlying molecular mechanism. In this mini-review, the ability of AMPs to synergize with different antibiotic classes or different natural compounds is examined. Furthermore, data on microbial resistance induction are reported to highlight the importance of antibiotic resistance in the fight against infections. Finally, the effects that sub-MIC levels of AMPs can have on the bacterial pathogenicity are summarized while showing how signaling pathways can be valid therapeutic targets for the treatment of infectious diseases. All these aspects support the high potential of AMPs as lead compounds for the development of new drugs with antibacterial and immunomodulatory activities.


2021 ◽  
Vol 54 (3) ◽  
pp. 1-42
Author(s):  
Divya Saxena ◽  
Jiannong Cao

Generative Adversarial Networks (GANs) is a novel class of deep generative models that has recently gained significant attention. GANs learn complex and high-dimensional distributions implicitly over images, audio, and data. However, there exist major challenges in training of GANs, i.e., mode collapse, non-convergence, and instability, due to inappropriate design of network architectre, use of objective function, and selection of optimization algorithm. Recently, to address these challenges, several solutions for better design and optimization of GANs have been investigated based on techniques of re-engineered network architectures, new objective functions, and alternative optimization algorithms. To the best of our knowledge, there is no existing survey that has particularly focused on the broad and systematic developments of these solutions. In this study, we perform a comprehensive survey of the advancements in GANs design and optimization solutions proposed to handle GANs challenges. We first identify key research issues within each design and optimization technique and then propose a new taxonomy to structure solutions by key research issues. In accordance with the taxonomy, we provide a detailed discussion on different GANs variants proposed within each solution and their relationships. Finally, based on the insights gained, we present promising research directions in this rapidly growing field.


2021 ◽  
Vol 251 ◽  
pp. 03055
Author(s):  
John Blue ◽  
Braden Kronheim ◽  
Michelle Kuchera ◽  
Raghuram Ramanujan

Detector simulation in high energy physics experiments is a key yet computationally expensive step in the event simulation process. There has been much recent interest in using deep generative models as a faster alternative to the full Monte Carlo simulation process in situations in which the utmost accuracy is not necessary. In this work we investigate the use of conditional Wasserstein Generative Adversarial Networks to simulate both hadronization and the detector response to jets. Our model takes the 4-momenta of jets formed from partons post-showering and pre-hadronization as inputs and predicts the 4-momenta of the corresponding reconstructed jet. Our model is trained on fully simulated tt events using the publicly available GEANT-based simulation of the CMS Collaboration. We demonstrate that the model produces accurate conditional reconstructed jet transverse momentum (pT) distributions over a wide range of pT for the input parton jet. Our model takes only a fraction of the time necessary for conventional detector simulation methods, running on a CPU in less than a millisecond per event.


Author(s):  
Johanna Kuhlin ◽  
Lina Davies Forsman ◽  
Mikael Mansjö ◽  
Michaela Jonsson Nordvall ◽  
Maria Wijkander ◽  
...  

Abstract Background Pyrazinamide (PZA) resistance in multidrug-resistant tuberculosis (MDR-TB) is common; yet, it is not clear how it affects interim and treatment outcomes. Although rarely performed, phenotypic drug susceptibility testing (pDST) is used to define PZA resistance, but genotypic DST (gDST) and minimum inhibitory concentration (MIC) could be beneficial. We aimed to assess the impact of PZA gDST and MIC on time to sputum culture conversion (SCC) and treatment outcome in patients with MDR-TB. Methods Clinical, microbiological, and treatment data were collected in this cohort study for all patients diagnosed with MDR-TB in Sweden from 1992–2014. MIC, pDST, and whole-genome sequencing of the pncA, rpsA, and panD genes were used to define PZA resistance. A Cox regression model was used for statistical analyses. Results Of 157 patients with MDR-TB, 56.1% (n = 88) had PZA-resistant strains and 49.7% (n = 78) were treated with PZA. In crude and adjusted analysis (hazard ratio [HR], 0.49; 95% conficence interval [CI], .29-.82; P = .007), PZA gDST resistance was associated with a 29-day longer time to SCC. A 2-fold decrease in dilutions of PZA MIC for PZA-susceptible strains showed no association with SCC in crude or adjusted analyses (HR, 0.98; 95% CI, .73–1.31; P = .89). MIC and gDST for PZA were not associated with treatment outcome. Conclusions In patients with MDR-TB, gDST PZA resistance was associated with a longer time to SCC. Rapid PZA gDST is important to identify patients who may benefit from PZA treatment.


2020 ◽  
Vol 34 (04) ◽  
pp. 4377-4384
Author(s):  
Ameya Joshi ◽  
Minsu Cho ◽  
Viraj Shah ◽  
Balaji Pokuri ◽  
Soumik Sarkar ◽  
...  

Generative Adversarial Networks (GANs), while widely successful in modeling complex data distributions, have not yet been sufficiently leveraged in scientific computing and design. Reasons for this include the lack of flexibility of GANs to represent discrete-valued image data, as well as the lack of control over physical properties of generated samples. We propose a new conditional generative modeling approach (InvNet) that efficiently enables modeling discrete-valued images, while allowing control over their parameterized geometric and statistical properties. We evaluate our approach on several synthetic and real world problems: navigating manifolds of geometric shapes with desired sizes; generation of binary two-phase materials; and the (challenging) problem of generating multi-orientation polycrystalline microstructures.


Author(s):  
Trung Le ◽  
Quan Hoang ◽  
Hung Vu ◽  
Tu Dinh Nguyen ◽  
Hung Bui ◽  
...  

Generative Adversarial Networks (GANs) are a powerful class of deep generative models. In this paper, we extend GAN to the problem of generating data that are not only close to a primary data source but also required to be different from auxiliary data sources. For this problem, we enrich both GANs' formulations and applications by introducing pushing forces that thrust generated samples away from given auxiliary data sources. We term our method Push-and-Pull GAN (P2GAN). We conduct extensive experiments to demonstrate the merit of P2GAN in two applications: generating data with constraints and addressing the mode collapsing problem. We use CIFAR-10, STL-10, and ImageNet datasets and compute Fréchet Inception Distance to evaluate P2GAN's effectiveness in addressing the mode collapsing problem. The results show that P2GAN outperforms the state-of-the-art baselines. For the problem of generating data with constraints, we show that P2GAN can successfully avoid generating specific features such as black hair.


2021 ◽  
Vol 4 ◽  
Author(s):  
Nathanaël Perraudin ◽  
Sandro Marcon ◽  
Aurelien Lucchi ◽  
Tomasz Kacprzak

Weak gravitational lensing mass maps play a crucial role in understanding the evolution of structures in the Universe and our ability to constrain cosmological models. The prediction of these mass maps is based on expensive N-body simulations, which can create a computational bottleneck for cosmological analyses. Simulation-based emulators of map summary statistics, such as the matter power spectrum and its covariance, are starting to play increasingly important role, as the analytical predictions are expected to reach their precision limits for upcoming experiments. Creating an emulator of the cosmological mass maps themselves, rather than their summary statistics, is a more challenging task. Modern deep generative models, such as Generative Adversarial Networks (GAN), have demonstrated their potential to achieve this goal. Most existing GAN approaches produce simulations for a fixed value of the cosmological parameters, which limits their practical applicability. We propose a novel conditional GAN model that is able to generate mass maps for any pair of matter density Ωm and matter clustering strength σ8, parameters which have the largest impact on the evolution of structures in the Universe, for a given source galaxy redshift distribution n(z). Our results show that our conditional GAN can interpolate efficiently within the space of simulated cosmologies, and generate maps anywhere inside this space with good visual quality high statistical accuracy. We perform an extensive quantitative comparison of the N-body and GAN -generated maps using a range of metrics: the pixel histograms, peak counts, power spectra, bispectra, Minkowski functionals, correlation matrices of the power spectra, the Multi-Scale Structural Similarity Index (MS-SSIM) and our equivalent of the Fréchet Inception Distance. We find a very good agreement on these metrics, with typical differences are &lt;5% at the center of the simulation grid, and slightly worse for cosmologies at the grid edges. The agreement for the bispectrum is slightly worse, on the &lt;20% level. This contribution is a step toward building emulators of mass maps directly, capturing both the cosmological signal and its variability. We make the code1 and the data2 publicly available.


2021 ◽  
Vol 8 (1) ◽  
pp. 3-31
Author(s):  
Yuan Xue ◽  
Yuan-Chen Guo ◽  
Han Zhang ◽  
Tao Xu ◽  
Song-Hai Zhang ◽  
...  

AbstractIn many applications of computer graphics, art, and design, it is desirable for a user to provide intuitive non-image input, such as text, sketch, stroke, graph, or layout, and have a computer system automatically generate photo-realistic images according to that input. While classically, works that allow such automatic image content generation have followed a framework of image retrieval and composition, recent advances in deep generative models such as generative adversarial networks (GANs), variational autoencoders (VAEs), and flow-based methods have enabled more powerful and versatile image generation approaches. This paper reviews recent works for image synthesis given intuitive user input, covering advances in input versatility, image generation methodology, benchmark datasets, and evaluation metrics. This motivates new perspectives on input representation and interactivity, cross fertilization between major image generation paradigms, and evaluation and comparison of generation methods.


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