scholarly journals Generative adversarial networks for construction of virtual populations of mechanistic models: simulations to study Omecamtiv Mecarbil action

2021 ◽  
Author(s):  
Jaimit Parikh ◽  
Timothy Rumbell ◽  
Xenia Butova ◽  
Tatiana Myachina ◽  
Jorge Corral Acero ◽  
...  
Keyword(s):  
Calcium Sensitivity ◽  
Mechanistic Modeling ◽  
Hill Coefficient ◽  
Generative Adversarial Networks ◽  
Model Parameters ◽  
Inverse Mapping ◽  
Generative Adversarial Network ◽  
Complex Biological System ◽  
Omecamtiv Mecarbil

AbstractBiophysical models are increasingly used to gain mechanistic insights by fitting and reproducing experimental and clinical data. The inherent variability in the recorded datasets, however, presents a key challenge. In this study, we present a novel approach, which integrates mechanistic modeling and machine learning to analyze in vitro cardiac mechanics data and solve the inverse problem of model parameter inference. We designed a novel generative adversarial network (GAN) and employed it to construct virtual populations of cardiac ventricular myocyte models in order to study the action of Omecamtiv Mecarbil (OM), a positive cardiac inotrope. Populations of models were calibrated from mechanically unloaded myocyte shortening recordings obtained in experiments on rat myocytes in the presence and absence of OM. The GAN was able to infer model parameters while incorporating prior information about which model parameters OM targets. The generated populations of models reproduced variations in myocyte contraction recorded during in vitro experiments and provided improved understanding of OM’s mechanism of action. Inverse mapping of the experimental data using our approach suggests a novel action of OM, whereby it modifies interactions between myosin and tropomyosin proteins. To validate our approach, the inferred model parameters were used to replicate other in vitro experimental protocols, such as skinned preparations demonstrating an increase in calcium sensitivity and a decrease in the Hill coefficient of the force–calcium (F–Ca) curve under OM action. Our approach thereby facilitated the identification of the mechanistic underpinnings of experimental observations and the exploration of different hypotheses regarding variability in this complex biological system.

scholarly journals Normalization of HE-stained histological images using cycle consistent generative adversarial networks

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Marlen Runz ◽  
Daniel Rusche ◽  
Stefan Schmidt ◽  
Martin R. Weihrauch ◽  
Jürgen Hesser ◽  
...  
Keyword(s):  
Image Acquisition ◽  
Similarity Measures ◽  
Staining Intensity ◽  
Generative Adversarial Networks ◽  
Target Domain ◽  
Inverse Mapping ◽  
Generative Adversarial Network ◽  
Data Set ◽  
Link Type ◽  
Histological Images

Abstract Background Histological images show strong variance (e.g. illumination, color, staining quality) due to differences in image acquisition, tissue processing, staining, etc. This can impede downstream image analysis such as staining intensity evaluation or classification. Methods to reduce these variances are called image normalization techniques. Methods In this paper, we investigate the potential of CycleGAN (cycle consistent Generative Adversarial Network) for color normalization in hematoxylin-eosin stained histological images using daily clinical data with consideration of the variability of internal staining protocol variations. The network consists of a generator network GB that learns to map an image X from a source domain A to a target domain B, i.e. GB:XA→XB. In addition, a discriminator network DB is trained to distinguish whether an image from domain B is real or generated. The same process is applied to another generator-discriminator pair (GA,DA), for the inverse mapping GA:XB→XA. Cycle consistency ensures that a generated image is close to its original when being mapped backwards (GA(GB(XA))≈XA and vice versa). We validate the CycleGAN approach on a breast cancer challenge and a follicular thyroid carcinoma data set for various stain variations. We evaluate the quality of the generated images compared to the original images using similarity measures. In addition, we apply stain normalization on pathological lymph node data from our institute and test the gain from normalization on a ResNet classifier pre-trained on the Camelyon16 data set. Results Qualitative results of the images generated by our network are compared to original color distributions. Our evaluation indicates that by mapping images to a target domain, the similarity training images from that domain improves up to 96%. We also achieve a high cycle consistency for the generator networks by obtaining similarity indices greater than 0.9. When applying the CycleGAN normalization to HE-stain images from our institute the kappa-value of the ResNet-model that is only trained on Camelyon16 data is increased more than 50%. Conclusions CycleGANs have proven to efficiently normalize HE-stained images. The approach compensates for deviations resulting from image acquisition (e.g. different scanning devices) as well as from tissue staining (e.g. different staining protocols), and thus overcomes the staining variations in images from various institutions.The code is publicly available at https://github.com/m4ln/stainTransfer_CycleGAN_pytorch. The data set supporting the solutions is available at 10.11588/data/8LKEZF.

CAMGAN: Combining attention mechanism generative adversarial networks for cartoon face style transfer

2021 ◽  
pp. 1-9
Author(s):  
Tao Zhang ◽  
Long Yu ◽  
Shengwei Tian
Keyword(s):  
Real World ◽  
Attention Mechanism ◽  
Generative Adversarial Networks ◽  
Model Parameters ◽  
Data Sets ◽  
Generative Adversarial Network ◽  
Style Transfer ◽  
Adversarial Network ◽  
Adversarial Networks ◽  
Image Translation

In this paper, we presents an apporch for real-world human face close-up images cartoonization. We use generative adversarial network combined with an attention mechanism to convert real-world face pictures and cartoon-style images as unpaired data sets. At present, the image-to-image translation model has been able to successfully transfer style and content. However, some problems still exist in the task of cartoonizing human faces:Hunman face has many details, and the content of the image is easy to lose details after the image is translated. the quality of the image generated by the model is defective. The model in this paper uses the generative adversarial network combined with the attention mechanism, and proposes a new generative adversarial network combined with the attention mechanism to deal with these problems. The channel attention mechanism is embedded between the upper and lower sampling layers of the generator network, to avoid increasing the complexity of the model while conveying the complete details of the underlying information. After comparing the experimental results of FID, PSNR, MSE three indicators and the size of the model parameters, the new model network proposed in this paper avoids the complexity of the model while achieving a good balance in the conversion task of style and content.

scholarly journals Designing Feature-Controlled Humanoid Antibody Discovery Libraries Using Generative Adversarial Networks

2020 ◽  
Author(s):  
Tileli Amimeur ◽  
Jeremy M. Shaver ◽  
Randal R. Ketchem ◽  
J. Alex Taylor ◽  
Rutilio H. Clark ◽  
...  
Keyword(s):  
Mhc Class Ii ◽  
In Silico ◽  
De Novo ◽  
Variable Region ◽  
Generative Adversarial Networks ◽  
Human Antibody ◽  
Generative Adversarial Network ◽  
Effective Response

ABSTRACTWe demonstrate the use of a Generative Adversarial Network (GAN), trained from a set of over 400,000 light and heavy chain human antibody sequences, to learn the rules of human antibody formation. The resulting model surpasses common in silico techniques by capturing residue diversity throughout the variable region, and is capable of generating extremely large, diverse libraries of novel antibodies that mimic somatically hypermutated human repertoire response. This method permits us to rationally design de novo humanoid antibody libraries with explicit control over various properties of our discovery library. Through transfer learning, we are able to bias the GAN to generate molecules with key properties of interest such as improved stability and developability, lower predicted MHC Class II binding, and specific complementarity-determining region (CDR) characteristics. These approaches also provide a mechanism to better study the complex relationships between antibody sequence and molecular behavior, both in vitro and in vivo. We validate our method by successfully expressing a proof-of-concept library of nearly 100,000 GAN-generated antibodies via phage display. We present the sequences and homology-model structures of example generated antibodies expressed in stable CHO pools and evaluated across multiple biophysical properties. The creation of discovery libraries using our in silico approach allows for the control of pharmaceutical properties such that these therapeutic antibodies can provide a more rapid and cost-effective response to biological threats.

scholarly journals Normalization of HE-Stained Histological Images using Cycle Consistent Generative Adversarial Networks

2021 ◽  
Author(s):  
Marlen Runz ◽  
Daniel Rusche ◽  
Martin R Weihrauch ◽  
Jürgen Hesser ◽  
Cleo-Aron Weis
Keyword(s):  
Image Acquisition ◽  
Similarity Measures ◽  
Staining Intensity ◽  
Generative Adversarial Networks ◽  
Target Domain ◽  
Inverse Mapping ◽  
Generative Adversarial Network ◽  
Source Domain ◽  
Adversarial Network ◽  
Histological Images

Abstract Background: Histological images show huge variance (e.g. illumination, color, staining quality) due to differences in image acquisition, tissue processing, staining, etc. The variance can impede many image analyzes such as staining intensity evaluation or classification. Methods to reduce these variances are gathered under the term image normalization. Methods: We present the application of CylceGAN - a cycle consistent Generative Adversarial Network for color normalization in hematoxylin-eosin stained histological images using typical clinical data including variability of internal staining. The network consists of a generator network GB that learns to map an image X from a source domain A to a target domain B, i.e. GB : XA → XB. In addition, a discriminator network DB is trained to distinguish whether an image from domain B is an original or generated one. The same process is applied to another generator-discriminator pair (GA, DA), for the inverse mapping GA : XB → XA. Cycle consistency ensures that the generated image is close to the original image when being mapped backwards (GA(GB(XA)) ≈ XA and vice versa). We validate the CycleGAN approach on a breast cancer challenge and a follicular thyroid carcinoma dataset for various stain variations. We evaluate the quality of the generated images compared to the original images using similarity measures. Results: We present qualitative results of the images generated by our network compared to the original color distributions. Our evaluation shows that by mapping images from a source domain to a target domain, the similarity to original images from the target domain improve up to 96%. We also achieve a high cycle consistency for the inverse mapping by obtaining similarity indices bigger than 0.9. Conclusions: CycleGANs have proven to efficiently normalize HE-stained images. The approach enables to compensate for deviations resulting from image acquisition (e.g. different scanning devices) as well as from tissue staining (e.g. different staining protocols), and thus overcomes the staining variations in images from various institutions. The code is publicly available at https://github.com/m4ln/stainTransfer_CycleGAN_pytorch. The dataset supporting the solutions is available at https://heidata.uni-heidelberg. de/privateurl.xhtml?token=12493b50-1538-4bdf-aca5-03352a1399a8.

scholarly journals Expanding functional protein sequence space using generative adversarial networks

2019 ◽  
Author(s):  
Donatas Repecka ◽  
Vykintas Jauniskis ◽  
Laurynas Karpus ◽  
Elzbieta Rembeza ◽  
Jan Zrimec ◽  
...  
Keyword(s):  
Protein Design ◽  
Sequence Space ◽  
Protein Sequence ◽  
Protein Function ◽  
De Novo ◽  
Protein Sequences ◽  
Generative Adversarial Networks ◽  
Functional Protein ◽  
Generative Adversarial Network

ABSTRACTDe novo protein design for catalysis of any desired chemical reaction is a long standing goal in protein engineering, due to the broad spectrum of technological, scientific and medical applications. Currently, mapping protein sequence to protein function is, however, neither computationionally nor experimentally tangible 1,2. Here we developed ProteinGAN, a specialised variant of the generative adversarial network 3 that is able to ‘learn’ natural protein sequence diversity and enables the generation of functional protein sequences. ProteinGAN learns the evolutionary relationships of protein sequences directly from the complex multidimensional amino acid sequence space and creates new, highly diverse sequence variants with natural-like physical properties. Using malate dehydrogenase as a template enzyme, we show that 24% of the ProteinGAN-generated and experimentally tested sequences are soluble and display wild-type level catalytic activity in the tested conditions in vitro, even in highly mutated (>100 mutations) sequences. ProteinGAN therefore demonstrates the potential of artificial intelligence to rapidly generate highly diverse novel functional proteins within the allowed biological constraints of the sequence space.

ORGANIC (1).pdf

2017 ◽  
Author(s):  
Benjamin Sanchez-Lengeling ◽  
Carlos Outeiral ◽  
Gabriel L. Guimaraes ◽  
Alan Aspuru-Guzik
Keyword(s):  
Machine Learning ◽  
Learning Community ◽  
Chemical Species ◽  
Material Design ◽  
Organic Photovoltaic ◽  
Generative Adversarial Networks ◽  
Generative Adversarial Network ◽  
Adversarial Network ◽  
Adversarial Networks ◽  
Photovoltaic Material

Molecular discovery seeks to generate chemical species tailored to very specific needs. In this paper, we present ORGANIC, a framework based on Objective-Reinforced Generative Adversarial Networks (ORGAN), capable of producing a distribution over molecular space that matches with a certain set of desirable metrics. This methodology combines two successful techniques from the machine learning community: a Generative Adversarial Network (GAN), to create non-repetitive sensible molecular species, and Reinforcement Learning (RL), to bias this generative distribution towards certain attributes. We explore several applications, from optimization of random physicochemical properties to candidates for drug discovery and organic photovoltaic material design.

scholarly journals Restoring Raindrops Using Attentive Generative Adversarial Networks

2021 ◽  
Vol 11 (15) ◽  
pp. 7034
Author(s):  
Hee-Deok Yang
Keyword(s):  
Weather Conditions ◽  
Recurrent Network ◽  
Generative Adversarial Networks ◽  
Navigation Systems ◽  
Vision Systems ◽  
Generative Adversarial Network ◽  
Network Layers ◽  
Adversarial Network ◽  
Adversarial Networks ◽  
Outdoor Vision

Artificial intelligence technologies and vision systems are used in various devices, such as automotive navigation systems, object-tracking systems, and intelligent closed-circuit televisions. In particular, outdoor vision systems have been applied across numerous fields of analysis. Despite their widespread use, current systems work well under good weather conditions. They cannot account for inclement conditions, such as rain, fog, mist, and snow. Images captured under inclement conditions degrade the performance of vision systems. Vision systems need to detect, recognize, and remove noise because of rain, snow, and mist to boost the performance of the algorithms employed in image processing. Several studies have targeted the removal of noise resulting from inclement conditions. We focused on eliminating the effects of raindrops on images captured with outdoor vision systems in which the camera was exposed to rain. An attentive generative adversarial network (ATTGAN) was used to remove raindrops from the images. This network was composed of two parts: an attentive-recurrent network and a contextual autoencoder. The ATTGAN generated an attention map to detect rain droplets. A de-rained image was generated by increasing the number of attentive-recurrent network layers. We increased the number of visual attentive-recurrent network layers in order to prevent gradient sparsity so that the entire generation was more stable against the network without preventing the network from converging. The experimental results confirmed that the extended ATTGAN could effectively remove various types of raindrops from images.

scholarly journals Prediction and analysis of multiple protein lysine modified sites based on conditional wasserstein generative adversarial networks

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Yingxi Yang ◽  
Hui Wang ◽  
Wen Li ◽  
Xiaobo Wang ◽  
Shizhao Wei ◽  
...  
Keyword(s):  
Correlation Coefficient ◽  
Sequence Data ◽  
Rapid Development ◽  
Pearson Correlation ◽  
Structural Features ◽  
Generative Adversarial Networks ◽  
Post Translational Modification ◽  
Generative Adversarial Network ◽  
Data Imbalance ◽  
Adversarial Network

Abstract Background Protein post-translational modification (PTM) is a key issue to investigate the mechanism of protein’s function. With the rapid development of proteomics technology, a large amount of protein sequence data has been generated, which highlights the importance of the in-depth study and analysis of PTMs in proteins. Method We proposed a new multi-classification machine learning pipeline MultiLyGAN to identity seven types of lysine modified sites. Using eight different sequential and five structural construction methods, 1497 valid features were remained after the filtering by Pearson correlation coefficient. To solve the data imbalance problem, Conditional Generative Adversarial Network (CGAN) and Conditional Wasserstein Generative Adversarial Network (CWGAN), two influential deep generative methods were leveraged and compared to generate new samples for the types with fewer samples. Finally, random forest algorithm was utilized to predict seven categories. Results In the tenfold cross-validation, accuracy (Acc) and Matthews correlation coefficient (MCC) were 0.8589 and 0.8376, respectively. In the independent test, Acc and MCC were 0.8549 and 0.8330, respectively. The results indicated that CWGAN better solved the existing data imbalance and stabilized the training error. Alternatively, an accumulated feature importance analysis reported that CKSAAP, PWM and structural features were the three most important feature-encoding schemes. MultiLyGAN can be found at https://github.com/Lab-Xu/MultiLyGAN. Conclusions The CWGAN greatly improved the predictive performance in all experiments. Features derived from CKSAAP, PWM and structure schemes are the most informative and had the greatest contribution to the prediction of PTM.

scholarly journals Stochastic Restoration of Heavily Compressed Musical Audio Using Generative Adversarial Networks

Electronics ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 1349
Author(s):  
Stefan Lattner ◽  
Javier Nistal
Keyword(s):  
Data Storage ◽  
Audio Signal ◽  
Human Perception ◽  
Generative Adversarial Networks ◽  
Audio Signals ◽  
Generative Adversarial Network ◽  
Adversarial Network ◽  
Extensive Evaluation ◽  
Listening Tests ◽  
Musical Audio

Lossy audio codecs compress (and decompress) digital audio streams by removing information that tends to be inaudible in human perception. Under high compression rates, such codecs may introduce a variety of impairments in the audio signal. Many works have tackled the problem of audio enhancement and compression artifact removal using deep-learning techniques. However, only a few works tackle the restoration of heavily compressed audio signals in the musical domain. In such a scenario, there is no unique solution for the restoration of the original signal. Therefore, in this study, we test a stochastic generator of a Generative Adversarial Network (GAN) architecture for this task. Such a stochastic generator, conditioned on highly compressed musical audio signals, could one day generate outputs indistinguishable from high-quality releases. Therefore, the present study may yield insights into more efficient musical data storage and transmission. We train stochastic and deterministic generators on MP3-compressed audio signals with 16, 32, and 64 kbit/s. We perform an extensive evaluation of the different experiments utilizing objective metrics and listening tests. We find that the models can improve the quality of the audio signals over the MP3 versions for 16 and 32 kbit/s and that the stochastic generators are capable of generating outputs that are closer to the original signals than those of the deterministic generators.

scholarly journals Enhanced Magnetic Resonance Image Synthesis with Contrast-Aware Generative Adversarial Networks

2021 ◽  
Vol 7 (8) ◽  
pp. 133
Author(s):  
Jonas Denck ◽  
Jens Guehring ◽  
Andreas Maier ◽  
Eva Rothgang
Keyword(s):  
Magnetic Resonance ◽  
Image Synthesis ◽  
Generative Adversarial Networks ◽  
Data Generation ◽  
Mr Images ◽  
Generative Adversarial Network ◽  
Radiology Training ◽  
Repetition Time ◽  
Echo Time ◽  
Image Orientation

A magnetic resonance imaging (MRI) exam typically consists of the acquisition of multiple MR pulse sequences, which are required for a reliable diagnosis. With the rise of generative deep learning models, approaches for the synthesis of MR images are developed to either synthesize additional MR contrasts, generate synthetic data, or augment existing data for AI training. While current generative approaches allow only the synthesis of specific sets of MR contrasts, we developed a method to generate synthetic MR images with adjustable image contrast. Therefore, we trained a generative adversarial network (GAN) with a separate auxiliary classifier (AC) network to generate synthetic MR knee images conditioned on various acquisition parameters (repetition time, echo time, and image orientation). The AC determined the repetition time with a mean absolute error (MAE) of 239.6 ms, the echo time with an MAE of 1.6 ms, and the image orientation with an accuracy of 100%. Therefore, it can properly condition the generator network during training. Moreover, in a visual Turing test, two experts mislabeled 40.5% of real and synthetic MR images, demonstrating that the image quality of the generated synthetic and real MR images is comparable. This work can support radiologists and technologists during the parameterization of MR sequences by previewing the yielded MR contrast, can serve as a valuable tool for radiology training, and can be used for customized data generation to support AI training.

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