Cancer. 2024 May 1;130(9):1546-1547. doi: 10.1002/cncr.35294.

NO ABSTRACT

PMID:38604987 | DOI:10.1002/cncr.35294

ISA Trans. 2024 Mar 30:S0019-0578(24)00141-1. doi: 10.1016/j.isatra.2024.03.033. Online ahead of print.

ABSTRACT

Motor bearing fault diagnosis is essential to guarantee production efficiency and avoid catastrophic accidents. Deep learning-based methods have been developed and widely used for fault diagnosis, and these methods have proven to be very effective in accurately diagnosing bearing faults. In this paper, study the application of generative adversarial networks (GANs) in motor bearing fault diagnosis to address the practical issue of insufficient fault data in industrial testing. Focus on the auxiliary classifier generative adversarial network (ACGAN), and the data expansion is carried out for small datasets. This paper present a novel transformer network and auxiliary classifier generative adversarial network (TRA-ACGAN) for motor bearing fault diagnosis, where the TRA-ACGAN combines an ACGAN with a transformer network to avoid the traditional iterative and convolutional structures. The attention mechanism is fully utilized to extract more effective features, and the dual-task coupling problem encountered in classical ACGANs is avoided. Experimental results with the CWRU dataset and the PU dataset in the field of motor bearing fault diagnosis demonstrate the suitability and superiority of the TRA-ACGAN.

PMID:38604873 | DOI:10.1016/j.isatra.2024.03.033

Br J Pharmacol. 2024 Apr 11. doi: 10.1111/bph.16377. Online ahead of print.

ABSTRACT

BACKGROUND AND PURPOSE: At present, the inhibition of staphyloxanthin biosynthesis has emerged as a prominent strategy in combating methicillin-resistant Staphylococcus aureus (MRSA) infection. Nonetheless, there remains a limited understanding regarding the bio-structural characteristics of staphyloxanthin biosynthetic enzymes, as well as the molecular mechanisms underlying the interaction between inhibitors and proteins. Furthermore, the functional scope of these inhibitors is relatively narrow.

EXPERIMENTAL APPROACH: In this study, we address these limitations by harnessing the power of deep learning techniques to construct the 3D structure of diapophytoene desaturase (CrtN). We perform efficient virtual screening and unveil alnustone as a potent inhibitor of CrtN. Further investigations employing molecular modelling, site-directed mutagenesis and biolayer interferometry (BLI) confirmed that alnustone binds to the catalytic active site of CrtN. Transcriptomic analysis reveals that alnustone significantly down-regulates genes associated with staphyloxanthin, histidine and peptidoglycan biosynthesis.

KEY RESULTS: Under the effects of alnustone, MRSA strains exhibit enhanced sensitivity to various antibiotics and the host immune system, accompanied by increased cell membrane permeability. In a mouse model of systemic MRSA infection, the combination of alnustone and antibiotics exhibited a significant therapeutic effect, leading to reduced bacterial colony counts and attenuated pathological damage.

CONCLUSION AND IMPLICATIONS: Alnustone, as a natural inhibitor targeting CrtN, exhibits outstanding antibacterial properties that are single-targeted yet multifunctional. This finding provides a novel strategy and theoretical basis for the development of drugs targeting staphyloxanthin producing bacteria.

PMID:38604611 | DOI:10.1111/bph.16377

Magn Reson Imaging. 2024 Apr 9:S0730-725X(24)00124-3. doi: 10.1016/j.mri.2024.04.010. Online ahead of print.

ABSTRACT

PURPOSE: To assess whether diffusion-weighted imaging (DWI) with Compressed SENSE (CS) and deep learning (DL-CS-DWI) can improve image quality and lesion detection in patients at risk for hepatocellular carcinoma (HCC).

METHODS: This single-center prospective study enrolled consecutive at-risk participants who underwent 3.0 T gadoxetate disodium-enhanced MRI. Conventional DWI was acquired using parallel imaging (PI) with SENSE (PI-DWI). In CS-DWI and DL-CS-DWI, CS but not PI with SENSE was used to accelerate the scan with 2.5 as the acceleration factor. Qualitative and quantitative image quality were independently assessed by two masked reviewers, and were compared using the Wilcoxon signed-rank test. The detection rates of clinically-relevant (LR-4/5/M based on the Liver Imaging Reporting and Data System v2018) liver lesions for each DWI sequence were independently evaluated by another two masked reviewers against their consensus assessments based on all available non-DWI sequences, and were compared by the McNemar test.

RESULTS: 67 participants (median age, 58.0 years; 56 males) with 197 clinically-relevant liver lesions were enrolled. Among the three DWI sequences, DL-CS-DWI showed the best qualitative and quantitative image qualities (p range, <0.001-0.039). For clinically-relevant liver lesions, the detection rates (91.4%-93.4%) of DL-CS-DWI showed no difference with CS-DWI (87.3%-89.8%, p = 0.230-0.231) but were superior to PI-DWI (82.7%-85.8%, p = 0.015-0.025). For lesions located in the hepatic dome, DL-CS-DWI demonstrated the highest detection rates (94.8%-97.4% vs 76.9%-79.5% vs 64.1%-69.2%, p = 0.002-0.045) among the three DWI sequences.

CONCLUSION: In patients at high-risk for HCC, DL-CS-DWI improved image quality and detection for clinically-relevant liver lesions, especially for the hepatic dome.

PMID:38604347 | DOI:10.1016/j.mri.2024.04.010

Methods Inf Med. 2024 Apr 11. doi: 10.1055/a-2305-2115. Online ahead of print.

ABSTRACT

OBJECTIVE: In this study, we propose a novel framework that utilizes deep learning and attention mechanisms to predict the radiographic progression of patellofemoral osteoarthritis (PFOA) over a period of seven years.

DESIGN: This study included subjects (1832 subjects, 3276 knees) from the baseline of the Multicenter Osteoarthritis Study (MOST). Patellofemoral joint regions-of interest were identified using an automated landmark detection tool (BoneFinder) on lateral knee X-rays. An end-to-end deep learning method was developed for predicting PFOA progression based on imaging data in a 5-fold cross-validation setting. To evaluate the performance of the models, a set of baselines based on known risk factors were developed and analyzed using gradient boosting machine (GBM). Risk factors included age, sex, BMI and WOMAC score, and the radiographic osteoarthritis stage of the tibiofemoral joint (KL score). Finally, to increase predictive power, we trained an ensemble model using both imaging and clinical data.

RESULTS: Among the individual models, the performance of our deep convolutional neural network attention model achieved the best performance with an AUC of 0.856 and AP of 0.431; slightly outperforming the deep learning approach without attention (AUC=0.832, AP= 0.4) and the best performing reference GBM model (AUC=0.767, AP= 0.334). The inclusion of imaging data and clinical variables in an ensemble model allowed statistically more powerful prediction of PFOA progression (AUC = 0.865, AP=0.447), although the clinical significance of this minor performance gain remains unknown. The spatial attention module improved the predictive performance of the backbone model, and the visual interpretation of attention maps focused on the joint space and the regions where osteophytes typically occur.

CONCLUSION: This study demonstrated the potential of machine learning models to predict the progression of PFOA using imaging and clinical variables. These models could be used to identify patients who are at high risk of progression and prioritize them for new treatments. However, even though the accuracy of the models were excellent in this study using the MOST dataset, they should be still validated using external patient cohorts in the future.

PMID:38604249 | DOI:10.1055/a-2305-2115

Phys Med Biol. 2024 Apr 11. doi: 10.1088/1361-6560/ad3dba. Online ahead of print.

ABSTRACT

Objective&#xD;Deep learning reconstruction (DLR) algorithms exhibit object-dependent resolution and noise performance. Thus, traditional geometric CT phantoms cannot fully capture the clinical imaging performance of DLR. This study uses a patient-derived 3D-printed PixelPrint lung phantom to evaluate a commercial DLR algorithm across a wide range of radiation dose levels.&#xD;&#xD;Method&#xD;The lung phantom used in this study is based on a patient chest CT scan containing ground glass opacities and was fabricated using PixelPrint 3D-printing technology. The phantom was placed inside two different size extension rings to mimic a small- and medium-sized patient and was scanned on a conventional CT scanner at exposures between 0.5 and 20 mGy. Each scan was reconstructed using filtered back projection (FBP), iterative reconstruction, and DLR at five levels of denoising. Image noise, contrast to noise ratio (CNR), root mean squared error (RMSE), structural similarity index (SSIM), and multi-scale SSIM (MS SSIM) were calculated for each image.&#xD;&#xD;Results&#xD;DLR demonstrated superior performance compared to FBP and iterative reconstruction for all measured metrics in both phantom sizes, with better performance for more aggressive denoising levels. DLR was estimated to reduce dose by 25-83% in the small phantom and by 50-83% in the medium phantom without decreasing image quality for any of the metrics measured in this study. These dose reduction estimates are more conservative compared to the estimates obtained when only considering noise and CNR. &#xD;&#xD;Conclusion&#xD;DLR has the capability of producing diagnostic image quality at up to 83% lower radiation dose, which can improve the clinical utility and viability of lower dose CT scans. Furthermore, the PixelPrint phantom used in this study offers an improved testing environment with more realistic tissue structures compared to traditional CT phantoms, allowing for structure-based image quality evaluation beyond noise and contrast-based assessments.

PMID:38604190 | DOI:10.1088/1361-6560/ad3dba

Phys Med Biol. 2024 Apr 11. doi: 10.1088/1361-6560/ad3dbc. Online ahead of print.

ABSTRACT

OBJECTIVE: Recently, deep learning models have been used to reconstruct parallel magnetic resonance (MR) images from undersampled k-space data. However, most existing approaches depend on large databases of fully sampled MR data for training, which can be challenging or sometimes infeasible to acquire in certain scenarios. The goal is to develop an effective alternative for improved reconstruction quality that does not rely on external training datasets.

APPROACH: We introduce a novel zero-shot dual-domain fusion unsupervised neural network (DFUSNN) for parallel MR imaging reconstruction without any external training datasets. We employ the Noise2Noise (N2N) network for the reconstruction in the k-space domain, integrates phase and coil sensitivity smoothness priors into the k-space N2N network, and uses an early stopping criterion to prevent overfitting. Additionally, we propose a dual-domain fusion method based on Bayesian optimization to enhance reconstruction quality efficiently.

RESULTS: Simulation experiments conducted on three datasets with different undersampling patterns showed that the DFUSNN outperforms all other competing unsupervised methods and the one-shot Hankel-k-space generative model (HKGM). The DFUSNN also achieves comparable results to the supervised Deep-SLR method.

SIGNIFICANCE: The novel DFUSNN model offers a viable solution for reconstructing high quality MR images without the need for external training datasets, thereby overcoming a major hurdle in scenarios where acquiring fully sampled MR data is difficult.

PMID:38604186 | DOI:10.1088/1361-6560/ad3dbc

Phys Med Biol. 2024 Apr 11. doi: 10.1088/1361-6560/ad3dbd. Online ahead of print.

ABSTRACT

Monte Carlo (MC) simulations are the benchmark for accurate radiotherapy dose calculations, notably in patient-specific high dose rate brachytherapy (HDR BT), in cases where considering tissue heterogeneities is critical. However, the lengthy computational time limits the practical application of MC simulations. Prior research used Deep Learning (DL) for dose prediction as an alternative to MC simulations. While accurate dose predictions akin to MC were attained, GPU limitations constrained these predictions to large voxels of 3mm × 3mm × 3mm. This study aimed to enable dose predictions as accurate as MC simulations in 1mm × 1mm × 1mm voxels within a clinically acceptable timeframe.&#xD;Approach: Computed tomography scans of 98 breast cancer patients treated with Iridium-192-based HDR BT were used: 70 for training, 14 for validation, and 14 for testing. A new cropping strategy based on the distance to the seed was devised to reduce the volume size, enabling efficient training of 3D DL models using 1 mm × 1 mm × 1 mm dose grids. Additionally, novel DL architecture with layer-level fusion were proposed to predict MC simulated dose to medium-in-medium (Dm,m). These architectures fuse information from TG-43 dose to water-in-water (Dw,w) with patient tissue composition at the layer-level. Different inputs describing patient body composition were investigated.&#xD;Main results: The proposed approach demonstrated state-of-the-art performance, on par with the MC Dm,m maps, but 300 times faster. The mean absolute percent error for dosimetric indices between the MC and DL-predicted complete treatment plans was 0.17%±0.15% for the planning target volume V100, 0.30%±0.32% for the skin D2cc, 0.82%±0.79% for the lung D2cc, 0.34%±0.29% for the chest wall D2cc and 1.08%±0.98% for the heart D2cc.&#xD;Significance: Unlike the time-consuming MC simulations, the proposed novel strategy efficiently converts TG-43 Dw,w maps into precise Dm,m maps at high resolution, enabling clinical integration.

PMID:38604185 | DOI:10.1088/1361-6560/ad3dbd

Physiol Meas. 2024 Apr 11. doi: 10.1088/1361-6579/ad3dbf. Online ahead of print.

ABSTRACT

Monitoring changes in human HRV (Heart Rate Variability) holds significant importance for protecting life and health.. Studies have shown that Imaging Photoplethysmography (IPPG) based on ordinary color cameras can detect the color change of the skin pixel caused by cardiopulmonary system. Most researchers employed deep learning IPPG algorithms to extract the Blood Volume Pulse (BVP) signal, analyzing it predominantly through the Heart Rate (HR). However, this approach often overlooks the inherent intricate time-frequency domain characteristics in the BVP signal, which cannot be comprehensively deduced solely from HR. The analysis of HRV metrics through the BVP signal is imperative.

APPROACH: In this paper, the transformation invariant loss function with distance equilibrium (TIDLE) loss function is applied to IPPG for the first time, and the details of BVP signal can be recovered better. In detail, TIDLE is tested in four commonly used IPPG deep learning models, which are DeepPhys, EfficientPhys, Physnet and TS_CAN, and compared with other three loss functions, which are MAE, MSE, NPCC.

MAIN RESULTS: The experiments demonstrate that MAE and MSE exhibit suboptimal performance in predicting LF/HF across the four models, achieving the Statistic of Mean Absolute Error (MAES) of 25.94% and 34.05%, respectively. In contrast, NPCC and TIDLE yielded more favorable results at 13.51% and 11.35%, respectively. Taking into consideration the morphological characteristics of the BVP signal, on the two optimal models for predicting HRV metrics, namely DeepPhys and TS_CAN, the Pearson coefficients for the BVP signals predicted by TIDLE in comparison to the gold-standard BVP signals achieved values of 0.627 and 0.605, respectively. In contrast, the results based on NPCC were notably lower, at only 0.545 and 0.533, respectively.

SIGNIFICANCE: This paper contributes significantly to the effective restoration of the morphology and frequency domain characteristics of the BVP signal.

PMID:38604181 | DOI:10.1088/1361-6579/ad3dbf

Phys Med Biol. 2024 Apr 11. doi: 10.1088/1361-6560/ad3db9. Online ahead of print.

ABSTRACT

Cardiac computed tomography is widely used for diagnosis of cardiovascular disease, the leading cause of morbidity and mortality in the world. Diagnostic performance depends strongly on the temporal resolution of the CT images. To image the beating heart, one can reduce the scanning time by acquiring limited-angle projections. However, this leads to increased image noise and limited-angle-related artifacts. The ability to reconstruct high quality images from limited-angle projections is highly desirable and remains a major challenge. With the development of deep learning networks, such as U-Net and transformer networks, progresses have been reached on image reconstruction and processing. Here we propose a hybrid model based on the U-Net and Swin-transformer (U-Swin) networks. The U-Net has the potential to restore structural information due to missing projection data and related artifacts, then the Swin-transformer can gather a detailed global feature distribution. Using synthetic XCAT and clinical cardiac COCA datasets, we demonstrate that our proposed method outperforms the state-of-the-art deep learning-based methods.

PMID:38604178 | DOI:10.1088/1361-6560/ad3db9

Leg Med (Tokyo). 2024 Apr 7;69:102444. doi: 10.1016/j.legalmed.2024.102444. Online ahead of print.

ABSTRACT

PURPOSE: The accurate age estimation of cadavers is essential for their identification. However, conventional methods fail to yield adequate age estimation especially in elderly cadavers. We developed a deep learning algorithm for age estimation on CT images of the vertebral column and checked its accuracy.

METHOD: For the development of our deep learning algorithm, we included 1,120 CT data of the vertebral column of 140 patients for each of 8 age decades. The deep learning model of regression analysis based on Visual Geometry Group-16 (VGG16) was improved in its estimation accuracy by bagging. To verify its accuracy, we applied our deep learning algorithm to estimate the age of 219 cadavers who had undergone postmortem CT (PMCT). The mean difference and the mean absolute error (MAE), the standard error of the estimate (SEE) between the known- and the estimated age, were calculated. Correlation analysis using the intraclass correlation coefficient (ICC) and Bland-Altman analysis were performed to assess differences between the known- and the estimated age.

RESULTS: For the 219 cadavers, the mean difference between the known- and the estimated age was 0.30 years; it was 4.36 years for the MAE, and 5.48 years for the SEE. The ICC (2,1) was 0.96 (95 % confidence interval: 0.95-0.97, p < 0.001). Bland-Altman analysis showed that there were no proportional or fixed errors (p = 0.08 and 0.41).

CONCLUSIONS: Our deep learning algorithm for estimating the age of 219 cadavers on CT images of the vertebral column was more accurate than conventional methods and highly useful.

PMID:38604090 | DOI:10.1016/j.legalmed.2024.102444

Mar Pollut Bull. 2024 Apr 10;202:116356. doi: 10.1016/j.marpolbul.2024.116356. Online ahead of print.

ABSTRACT

In this study, we focus on the development and validation of a deep learning (long short-term memory, LSTM)-based algorithm to predict the accidental spreading of LSFO (low sulfur fuel oil) on the water surface. The data for the training was obtained by numerical simulations of artificial geometries with different configurations of islands and shorelines and wind speeds (2.0-8.0 m/s). For simulating the spread of oils in O(102) km scales, the volume of fluid and discrete phase models were adopted, and the kinematic variables of particle location, particle velocity, and water velocity were collected as input features for LSTM model. The predicted spreading pattern of LSFO matched well with the simulation (less than 10 % in terms of the mean absolute error for the untrained data). Finally, we applied the model to the Wakashio LSFO spill accident, considering actual geometry and weather information, which confirmed the practical feasibility of the present model.

PMID:38604079 | DOI:10.1016/j.marpolbul.2024.116356

PLoS One. 2024 Apr 11;19(4):e0300622. doi: 10.1371/journal.pone.0300622. eCollection 2024.

ABSTRACT

Breast cancer is one of the most often diagnosed cancers in women, and identifying breast cancer histological images is an essential challenge in automated pathology analysis. According to research, the global BrC is around 12% of all cancer cases. Furthermore, around 25% of women suffer from BrC. Consequently, the prediction of BrC depends critically on the quick and precise processing of imaging data. The primary reason deep learning models are used in breast cancer detection is that they can produce findings more quickly and accurately than current machine learning-based techniques. Using a BreakHis dataset, we demonstrated in this work the viability of automatically identifying and classifying BrC. The first stage is pre-processing, which employs an Adaptive Switching Modified Decision Based Unsymmetrical Trimmed Median Filter (ASMDBUTMF) to remove high-density noise. After the image has been pre-processed, it is segmented using the Thresholding Level set approach. Next, we propose a hybrid chaotic sand cat optimization technique, together with the Remora Optimization Algorithm (ROA) for feature selection. The suggested strategy facilitates the acquisition of precise functionality attributes, hence simplifying the detection procedure. Additionally, it aids in resolving problems pertaining to global optimization. Following the selection, the best characteristics proceed to the categorization procedure. A DL classifier called the Conditional Variation Autoencoder is used to discriminate between cancerous and benign tumors while categorizing them. Consequently, a classification accuracy of 99.4%, Precision of 99.2%, Recall of 99.1%, F- score of 99%, Specificity of 99.14%, FDR of 0.54, FNR of 0.001, FPR of 0.002, MCC of 0.98 and NPV of 0.99 were obtained using the proposed approach. Furthermore, compared to other research using the current BreakHis dataset, the results of our research are more desirable.

PMID:38603682 | DOI:10.1371/journal.pone.0300622

PLoS One. 2024 Apr 11;19(4):e0302024. doi: 10.1371/journal.pone.0302024. eCollection 2024.

ABSTRACT

Cardiovascular diseases remain the leading global cause of mortality. Age is an important covariate whose effect is most easily investigated in a healthy cohort to properly distinguish the former from disease-related changes. Traditionally, most of such insights have been drawn from the analysis of electrocardiogram (ECG) feature changes in individuals as they age. However, these features, while informative, may potentially obscure underlying data relationships. In this paper we present the following contributions: (1) We employ a deep-learning model and a tree-based model to analyze ECG data from a robust dataset of healthy individuals across varying ages in both raw signals and ECG feature format. (2) We use explainable AI methods to identify the most discriminative ECG features across age groups.(3) Our analysis with tree-based classifiers reveals age-related declines in inferred breathing rates and identifies notably high SDANN values as indicative of elderly individuals, distinguishing them from younger adults. (4) Furthermore, the deep-learning model underscores the pivotal role of the P-wave in age predictions across all age groups, suggesting potential changes in the distribution of different P-wave types with age. These findings shed new light on age-related ECG changes, offering insights that transcend traditional feature-based approaches.

PMID:38603660 | DOI:10.1371/journal.pone.0302024

Diabetes Obes Metab. 2024 Apr 11. doi: 10.1111/dom.15578. Online ahead of print.

ABSTRACT

AIM: To develop and employ machine learning (ML) algorithms to analyse electrocardiograms (ECGs) for the diagnosis of cardiac autonomic neuropathy (CAN).

MATERIALS AND METHODS: We used motif and discord extraction techniques, alongside long short-term memory networks, to analyse 12-lead, 10-s ECG tracings to detect CAN in patients with diabetes. The performance of these methods with the support vector machine classification model was evaluated using 10-fold cross validation with the following metrics: accuracy, precision, recall, F1 score, and area under the receiver-operating characteristic curve (AUC).

RESULTS: Among 205 patients (mean age 54 ± 17 years, 54% female), 100 were diagnosed with CAN, including 38 with definite or severe CAN (dsCAN) and 62 with early CAN (eCAN). The best model performance for dsCAN classification was achieved using both motifs and discords, with an accuracy of 0.92, an F1 score of 0.92, a recall at 0.94, a precision of 0.91, and an excellent AUC of 0.93 (95% confidence interval [CI] 0.91-0.94). For the detection of any stage of CAN, the approach combining motifs and discords yielded the best results, with an accuracy of 0.65, F1 score of 0.68, a recall of 0.75, a precision of 0.68, and an AUC of 0.68 (95% CI 0.54-0.81).

CONCLUSION: Our study highlights the potential of using ML techniques, particularly motifs and discords, to effectively detect dsCAN in patients with diabetes. This approach could be applied in large-scale screening of CAN, particularly to identify definite/severe CAN where cardiovascular risk factor modification may be initiated.

PMID:38603589 | DOI:10.1111/dom.15578

Int J High Perform Comput Appl. 2022 Nov;36(5-6):587-602. doi: 10.1177/10943420221121804.

ABSTRACT

The COVID-19 pandemic highlights the need for computational tools to automate and accelerate drug design for novel protein targets. We leverage deep learning language models to generate and score drug candidates based on predicted protein binding affinity. We pre-trained a deep learning language model (BERT) on ∼9.6 billion molecules and achieved peak performance of 603 petaflops in mixed precision. Our work reduces pre-training time from days to hours, compared to previous efforts with this architecture, while also increasing the dataset size by nearly an order of magnitude. For scoring, we fine-tuned the language model using an assembled set of thousands of protein targets with binding affinity data and searched for inhibitors of specific protein targets, SARS-CoV-2 Mpro and PLpro. We utilized a genetic algorithm approach for finding optimal candidates using the generation and scoring capabilities of the language model. Our generalizable models accelerate the identification of inhibitors for emerging therapeutic targets.

PMID:38603308 | PMC:PMC9548488 | DOI:10.1177/10943420221121804

Int J High Perform Comput Appl. 2021 Sep;35(5):432-451. doi: 10.1177/10943420211006452.

ABSTRACT

We develop a generalizable AI-driven workflow that leverages heterogeneous HPC resources to explore the time-dependent dynamics of molecular systems. We use this workflow to investigate the mechanisms of infectivity of the SARS-CoV-2 spike protein, the main viral infection machinery. Our workflow enables more efficient investigation of spike dynamics in a variety of complex environments, including within a complete SARS-CoV-2 viral envelope simulation, which contains 305 million atoms and shows strong scaling on ORNL Summit using NAMD. We present several novel scientific discoveries, including the elucidation of the spike's full glycan shield, the role of spike glycans in modulating the infectivity of the virus, and the characterization of the flexible interactions between the spike and the human ACE2 receptor. We also demonstrate how AI can accelerate conformational sampling across different systems and pave the way for the future application of such methods to additional studies in SARS-CoV-2 and other molecular systems.

PMID:38603008 | PMC:PMC8064023 | DOI:10.1177/10943420211006452

J Chem Inf Model. 2024 Apr 11. doi: 10.1021/acs.jcim.4c00212. Online ahead of print.

ABSTRACT

Many biological functions are mediated by large complexes formed by multiple proteins and other cellular macromolecules. Recent progress in experimental structure determination, as well as in integrative modeling and protein structure prediction using deep learning approaches, has resulted in a rapid increase in the number of solved multiprotein assemblies. However, the assembly process of large complexes from their components is much less well-studied. We introduce a rapid computational structure-based (SB) model, GoCa, that allows to follow the assembly process of large multiprotein complexes based on a known native structure. Beyond existing SB Go̅-type models, it distinguishes between intra- and intersubunit interactions, allowing us to include coupled folding and binding. It accounts automatically for the permutation of identical subunits in a complex and allows the definition of multiple minima (native) structures in the case of proteins that undergo global transitions during assembly. The model is successfully tested on several multiprotein complexes. The source code of the GoCa program including a tutorial is publicly available on Github: https://github.com/ZachariasLab/GoCa. We also provide a web source that allows users to quickly generate the necessary input files for a GoCa simulation: https://goca.t38webservices.nat.tum.de.

PMID:38602938 | DOI:10.1021/acs.jcim.4c00212

PLoS Negl Trop Dis. 2024 Apr 11;18(4):e0012041. doi: 10.1371/journal.pntd.0012041. eCollection 2024 Apr.

ABSTRACT

BACKGROUND: Infections caused by soil-transmitted helminths (STHs) are the most prevalent neglected tropical diseases and result in a major disease burden in low- and middle-income countries, especially in school-aged children. Improved diagnostic methods, especially for light intensity infections, are needed for efficient, control and elimination of STHs as a public health problem, as well as STH management. Image-based artificial intelligence (AI) has shown promise for STH detection in digitized stool samples. However, the diagnostic accuracy of AI-based analysis of entire microscope slides, so called whole-slide images (WSI), has previously not been evaluated on a sample-level in primary healthcare settings in STH endemic countries.

METHODOLOGY/PRINCIPAL FINDINGS: Stool samples (n = 1,335) were collected during 2020 from children attending primary schools in Kwale County, Kenya, prepared according to the Kato-Katz method at a local primary healthcare laboratory and digitized with a portable whole-slide microscopy scanner and uploaded via mobile networks to a cloud environment. The digital samples of adequate quality (n = 1,180) were split into a training (n = 388) and test set (n = 792) and a deep-learning system (DLS) developed for detection of STHs. The DLS findings were compared with expert manual microscopy and additional visual assessment of the digital samples in slides with discordant results between the methods. Manual microscopy detected 15 (1.9%) Ascaris lumbricoides, 172 (21.7%) Tricuris trichiura and 140 (17.7%) hookworm (Ancylostoma duodenale or Necator americanus) infections in the test set. Importantly, more than 90% of all STH positive cases represented light intensity infections. With manual microscopy as the reference standard, the sensitivity of the DLS as the index test for detection of A. lumbricoides, T. trichiura and hookworm was 80%, 92% and 76%, respectively. The corresponding specificity was 98%, 90% and 95%. Notably, in 79 samples (10%) classified as negative by manual microscopy for a specific species, STH eggs were detected by the DLS and confirmed correct by visual inspection of the digital samples.

CONCLUSIONS/SIGNIFICANCE: Analysis of digitally scanned stool samples with the DLS provided high diagnostic accuracy for detection of STHs. Importantly, a substantial number of light intensity infections were missed by manual microscopy but detected by the DLS. Thus, analysis of WSIs with image-based AI may provide a future tool for improved detection of STHs in a primary healthcare setting, which in turn could facilitate monitoring and evaluation of control programs.

PMID:38602896 | DOI:10.1371/journal.pntd.0012041

IEEE Trans Pattern Anal Mach Intell. 2024 Apr 11;PP. doi: 10.1109/TPAMI.2024.3387399. Online ahead of print.

ABSTRACT

In this paper, we propose a general deep learning training framework XGrad which introduces weight prediction into the popular gradient-based optimizers to boost their convergence and generalization when training the deep neural network (DNN) models. In particular, ahead of each mini-batch training, the future weights are predicted according to the update rule of the used optimizer and are then applied to both the forward pass and backward propagation. In this way, during the whole training period, the optimizer always utilizes the gradients w.r.t. the future weights to update the DNN parameters, making the gradient-based optimizer achieve better convergence and generalization compared to the original optimizer without weight prediction. XGrad is rather straightforward to implement yet pretty effective in boosting the convergence of gradient-based optimizers and the accuracy of DNN models. Empirical results concerning five popular optimizers including SGD with momentum, Adam, AdamW, AdaBelief, and AdaM3 demonstrate the effectiveness of our proposal. The experimental results validate that XGrad can attain higher model accuracy than the baseline optimizers when training the DNN models. The code of XGrad will be available at: https://github.com/guanleics/XGrad.

PMID:38602857 | DOI:10.1109/TPAMI.2024.3387399