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1.
Nat Commun ; 15(1): 4690, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824132

Accurate identification of genetic alterations in tumors, such as Fibroblast Growth Factor Receptor, is crucial for treating with targeted therapies; however, molecular testing can delay patient care due to the time and tissue required. Successful development, validation, and deployment of an AI-based, biomarker-detection algorithm could reduce screening cost and accelerate patient recruitment. Here, we develop a deep-learning algorithm using >3000 H&E-stained whole slide images from patients with advanced urothelial cancers, optimized for high sensitivity to avoid ruling out trial-eligible patients. The algorithm is validated on a dataset of 350 patients, achieving an area under the curve of 0.75, specificity of 31.8% at 88.7% sensitivity, and projected 28.7% reduction in molecular testing. We successfully deploy the system in a non-interventional study comprising 89 global study clinical sites and demonstrate its potential to prioritize/deprioritize molecular testing resources and provide substantial cost savings in the drug development and clinical settings.


Algorithms , Deep Learning , Humans , Biomarkers, Tumor/metabolism , Biomarkers, Tumor/genetics , Clinical Trials as Topic , Urinary Bladder Neoplasms/pathology , Urinary Bladder Neoplasms/genetics , Urinary Bladder Neoplasms/diagnosis , Male , Female , Patient Selection , Urologic Neoplasms/pathology , Urologic Neoplasms/diagnosis , Urologic Neoplasms/genetics
2.
Sci Rep ; 14(1): 12601, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824162

Data categorization is a top concern in medical data to predict and detect illnesses; thus, it is applied in modern healthcare informatics. In modern informatics, machine learning and deep learning models have enjoyed great attention for categorizing medical data and improving illness detection. However, the existing techniques, such as features with high dimensionality, computational complexity, and long-term execution duration, raise fundamental problems. This study presents a novel classification model employing metaheuristic methods to maximize efficient positives on Chronic Kidney Disease diagnosis. The medical data is initially massively pre-processed, where the data is purified with various mechanisms, including missing values resolution, data transformation, and the employment of normalization procedures. The focus of such processes is to leverage the handling of the missing values and prepare the data for deep analysis. We adopt the Binary Grey Wolf Optimization method, a reliable subset selection feature using metaheuristics. This operation is aimed at improving illness prediction accuracy. In the classification step, the model adopts the Extreme Learning Machine with hidden nodes through data optimization to predict the presence of CKD. The complete classifier evaluation employs established measures, including recall, specificity, kappa, F-score, and accuracy, in addition to the feature selection. Data related to the study show that the proposed approach records high levels of accuracy, which is better than the existing models.


Medical Informatics , Renal Insufficiency, Chronic , Humans , Renal Insufficiency, Chronic/diagnosis , Medical Informatics/methods , Machine Learning , Deep Learning , Algorithms , Male , Female , Middle Aged
3.
Sci Rep ; 14(1): 12630, 2024 Jun 02.
Article En | MEDLINE | ID: mdl-38824210

In this study, we present the development of a fine structural human phantom designed specifically for applications in dentistry. This research focused on assessing the viability of applying medical computer vision techniques to the task of segmenting individual teeth within a phantom. Using a virtual cone-beam computed tomography (CBCT) system, we generated over 170,000 training datasets. These datasets were produced by varying the elemental densities and tooth sizes within the human phantom, as well as varying the X-ray spectrum, noise intensity, and projection cutoff intensity in the virtual CBCT system. The deep-learning (DL) based tooth segmentation model was trained using the generated datasets. The results demonstrate an agreement with manual contouring when applied to clinical CBCT data. Specifically, the Dice similarity coefficient exceeded 0.87, indicating the robust performance of the developed segmentation model even when virtual imaging was used. The present results show the practical utility of virtual imaging techniques in dentistry and highlight the potential of medical computer vision for enhancing precision and efficiency in dental imaging processes.


Cone-Beam Computed Tomography , Phantoms, Imaging , Tooth , Humans , Tooth/diagnostic imaging , Tooth/anatomy & histology , Cone-Beam Computed Tomography/methods , Dentistry/methods , Image Processing, Computer-Assisted/methods , Deep Learning
4.
Sci Rep ; 14(1): 12623, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824208

Crowd flow prediction has been studied for a variety of purposes, ranging from the private sector such as location selection of stores according to the characteristics of commercial districts and customer-tailored marketing to the public sector for social infrastructure design such as transportation networks. Its importance is even greater in light of the spread of contagious diseases such as COVID-19. In many cases, crowd flow can be divided into subgroups by common characteristics such as gender, age, location type, etc. If we use such hierarchical structure of the data effectively, we can improve prediction accuracy of crowd flow for subgroups. But the existing prediction models do not consider such hierarchical structure of the data. In this study, we propose a deep learning model based on global-local structure of the crowd flow data, which utilizes the overall(global) and subdivided by the types of sites(local) crowd flow data simultaneously to predict the crowd flow of each subgroup. The experiment result shows that the proposed model improves the prediction accuracy of each sub-divided subgroup by 5.2% (Table 5 Cat #9)-45.95% (Table 11 Cat #5), depending on the data set. This result comes from the comparison with the related works under the same condition that use target category data to predict each subgroup. In addition, when we refine the global data composition by considering the correlation between subgroups and excluding low correlated subgroups, the prediction accuracy is further improved by 5.6-48.65%.


COVID-19 , Crowding , Deep Learning , Humans , COVID-19/epidemiology , SARS-CoV-2
5.
Sci Rep ; 14(1): 12615, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824217

Standard clinical practice to assess fetal well-being during labour utilises monitoring of the fetal heart rate (FHR) using cardiotocography. However, visual evaluation of FHR signals can result in subjective interpretations leading to inter and intra-observer disagreement. Therefore, recent studies have proposed deep-learning-based methods to interpret FHR signals and detect fetal compromise. These methods have typically focused on evaluating fixed-length FHR segments at the conclusion of labour, leaving little time for clinicians to intervene. In this study, we propose a novel FHR evaluation method using an input length invariant deep learning model (FHR-LINet) to progressively evaluate FHR as labour progresses and achieve rapid detection of fetal compromise. Using our FHR-LINet model, we obtained approximately 25% reduction in the time taken to detect fetal compromise compared to the state-of-the-art multimodal convolutional neural network while achieving 27.5%, 45.0%, 56.5% and 65.0% mean true positive rate at 5%, 10%, 15% and 20% false positive rate respectively. A diagnostic system based on our approach could potentially enable earlier intervention for fetal compromise and improve clinical outcomes.


Cardiotocography , Deep Learning , Heart Rate, Fetal , Heart Rate, Fetal/physiology , Humans , Pregnancy , Female , Cardiotocography/methods , Neural Networks, Computer , Fetal Monitoring/methods , Signal Processing, Computer-Assisted , Fetus
6.
Sci Rep ; 14(1): 12598, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824219

To tackle the difficulty of extracting features from one-dimensional spectral signals using traditional spectral analysis, a metabolomics analysis method is proposed to locate two-dimensional correlated spectral feature bands and combine it with deep learning classification for wine origin traceability. Metabolomics analysis was performed on 180 wine samples from 6 different wine regions using UPLC-Q-TOF-MS. Indole, Sulfacetamide, and caffeine were selected as the main differential components. By analyzing the molecular structure of these components and referring to the main functional groups on the infrared spectrum, characteristic band regions with wavelengths in the range of 1000-1400 nm and 1500-1800 nm were selected. Draw two-dimensional correlation spectra (2D-COS) separately, generate synchronous correlation spectra and asynchronous correlation spectra, establish convolutional neural network (CNN) classification models, and achieve the purpose of wine origin traceability. The experimental results demonstrate that combining two segments of two-dimensional characteristic spectra determined by metabolomics screening with convolutional neural networks yields optimal classification results. This validates the effectiveness of using metabolomics screening to determine spectral feature regions in tracing wine origin. This approach effectively removes irrelevant variables while retaining crucial chemical information, enhancing spectral resolution. This integrated approach strengthens the classification model's understanding of samples, significantly increasing accuracy.


Deep Learning , Metabolomics , Wine , Wine/analysis , Metabolomics/methods , Neural Networks, Computer , Chromatography, High Pressure Liquid/methods , Mass Spectrometry/methods
7.
J Orthop Surg Res ; 19(1): 324, 2024 May 31.
Article En | MEDLINE | ID: mdl-38822361

BACKGROUND: The patellar height index is important; however, the measurement procedures are time-consuming and prone to significant variability among and within observers. We developed a deep learning-based automatic measurement system for the patellar height and evaluated its performance and generalization ability to accurately measure the patellar height index. METHODS: We developed a dataset containing 3,923 lateral knee X-ray images. Notably, all X-ray images were from three tertiary level A hospitals, and 2,341 cases were included in the analysis after screening. By manually labeling key points, the model was trained using the residual network (ResNet) and high-resolution network (HRNet) for human pose estimation architectures to measure the patellar height index. Various data enhancement techniques were used to enhance the robustness of the model. The root mean square error (RMSE), object keypoint similarity (OKS), and percentage of correct keypoint (PCK) metrics were used to evaluate the training results. In addition, we used the intraclass correlation coefficient (ICC) to assess the consistency between manual and automatic measurements. RESULTS: The HRNet model performed excellently in keypoint detection tasks by comparing different deep learning models. Furthermore, the pose_hrnet_w48 model was particularly outstanding in the RMSE, OKS, and PCK metrics, and the Insall-Salvati index (ISI) automatically calculated by this model was also highly consistent with the manual measurements (intraclass correlation coefficient [ICC], 0.809-0.885). This evidence demonstrates the accuracy and generalizability of this deep learning system in practical applications. CONCLUSION: We successfully developed a deep learning-based automatic measurement system for the patellar height. The system demonstrated accuracy comparable to that of experienced radiologists and a strong generalizability across different datasets. It provides an essential tool for assessing and treating knee diseases early and monitoring and rehabilitation after knee surgery. Due to the potential bias in the selection of datasets in this study, different datasets should be examined in the future to optimize the model so that it can be reliably applied in clinical practice. TRIAL REGISTRATION: The study was registered at the Medical Research Registration and Filing Information System (medicalresearch.org.cn) MR-61-23-013065. Date of registration: May 04, 2023 (retrospectively registered).


Deep Learning , Patella , Humans , Patella/diagnostic imaging , Patella/anatomy & histology , Retrospective Studies , Male , Female , Automation , Radiography/methods , Middle Aged , Adult
8.
BMC Infect Dis ; 24(1): 551, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824500

BACKGROUND: Leishmaniasis, an illness caused by protozoa, accounts for a substantial number of human fatalities globally, thereby emerging as one of the most fatal parasitic diseases. The conventional methods employed for detecting the Leishmania parasite through microscopy are not only time-consuming but also susceptible to errors. Therefore, the main objective of this study is to develop a model based on deep learning, a subfield of artificial intelligence, that could facilitate automated diagnosis of leishmaniasis. METHODS: In this research, we introduce LeishFuNet, a deep learning framework designed for detecting Leishmania parasites in microscopic images. To enhance the performance of our model through same-domain transfer learning, we initially train four distinct models: VGG19, ResNet50, MobileNetV2, and DenseNet 169 on a dataset related to another infectious disease, COVID-19. These trained models are then utilized as new pre-trained models and fine-tuned on a set of 292 self-collected high-resolution microscopic images, consisting of 138 positive cases and 154 negative cases. The final prediction is generated through the fusion of information analyzed by these pre-trained models. Grad-CAM, an explainable artificial intelligence technique, is implemented to demonstrate the model's interpretability. RESULTS: The final results of utilizing our model for detecting amastigotes in microscopic images are as follows: accuracy of 98.95 1.4%, specificity of 98 2.67%, sensitivity of 100%, precision of 97.91 2.77%, F1-score of 98.92 1.43%, and Area Under Receiver Operating Characteristic Curve of 99 1.33. CONCLUSION: The newly devised system is precise, swift, user-friendly, and economical, thus indicating the potential of deep learning as a substitute for the prevailing leishmanial diagnostic techniques.


Deep Learning , Leishmania , Leishmaniasis , Microscopy , Telemedicine , Humans , Leishmaniasis/parasitology , Leishmaniasis/diagnosis , Leishmania/isolation & purification , Microscopy/methods , COVID-19 , SARS-CoV-2/isolation & purification
9.
Biomed Eng Online ; 23(1): 50, 2024 Jun 01.
Article En | MEDLINE | ID: mdl-38824547

BACKGROUND: Over 60% of epilepsy patients globally are children, whose early diagnosis and treatment are critical for their development and can substantially reduce the disease's burden on both families and society. Numerous algorithms for automated epilepsy detection from EEGs have been proposed. Yet, the occurrence of epileptic seizures during an EEG exam cannot always be guaranteed in clinical practice. Models that exclusively use seizure EEGs for detection risk artificially enhanced performance metrics. Therefore, there is a pressing need for a universally applicable model that can perform automatic epilepsy detection in a variety of complex real-world scenarios. METHOD: To address this problem, we have devised a novel technique employing a temporal convolutional neural network with self-attention (TCN-SA). Our model comprises two primary components: a TCN for extracting time-variant features from EEG signals, followed by a self-attention (SA) layer that assigns importance to these features. By focusing on key features, our model achieves heightened classification accuracy for epilepsy detection. RESULTS: The efficacy of our model was validated on a pediatric epilepsy dataset we collected and on the Bonn dataset, attaining accuracies of 95.50% on our dataset, and 97.37% (A v. E), and 93.50% (B vs E), respectively. When compared with other deep learning architectures (temporal convolutional neural network, self-attention network, and standardized convolutional neural network) using the same datasets, our TCN-SA model demonstrated superior performance in the automated detection of epilepsy. CONCLUSION: The proven effectiveness of the TCN-SA approach substantiates its potential as a valuable tool for the automated detection of epilepsy, offering significant benefits in diverse and complex real-world clinical settings.


Electroencephalography , Epilepsy , Neural Networks, Computer , Epilepsy/diagnosis , Humans , Signal Processing, Computer-Assisted , Automation , Child , Deep Learning , Diagnosis, Computer-Assisted/methods , Time Factors
10.
Technol Cancer Res Treat ; 23: 15330338241256594, 2024.
Article En | MEDLINE | ID: mdl-38808514

Purpose: Intensity-modulated radiotherapy (IMRT) is currently the most important treatment method for nasopharyngeal carcinoma (NPC). This study aimed to enhance prediction accuracy by incorporating dose information into a deep convolutional neural network (CNN) using a multichannel input method. Methods: A target conformal plan (TCP) was created based on the maximum planning target volume (PTV). Input data included TCP dose distribution, images, target structures, and organ-at-risk (OAR) information. The role of target conformal plan dose (TCPD) was assessed by comparing the TCPD-CNN (with dose information) and NonTCPD-CNN models (without dose information) using statistical analyses with the ranked Wilcoxon test (P < .05 considered significant). Results: The TCPD-CNN model showed no statistical differences in predicted target indices, except for PTV60, where differences in the D98% indicator were < 0.5%. For OARs, there were no significant differences in predicted results, except for some small-volume or closely located OARs. On comparing TCPD-CNN and NonTCPD-CNN models, TCPD-CNN's dose-volume histograms closely resembled clinical plans with higher similarity index. Mean dose differences for target structures (predicted TCPD-CNN and NonTCPD-CNN results) were within 3% of the maximum prescription dose for both models. TCPD-CNN and NonTCPD-CNN outcomes were 67.9% and 54.2%, respectively. 3D gamma pass rates of the target structures and the entire body were higher in TCPD-CNN than in the NonTCPD-CNN models (P < .05). Additional evaluation on previously unseen volumetric modulated arc therapy plans revealed that average 3D gamma pass rates of the target structures were larger than 90%. Conclusions: This study presents a novel framework for dose distribution prediction using deep learning and multichannel input, specifically incorporating TCPD information, enhancing prediction accuracy for IMRT in NPC treatment.


Deep Learning , Nasopharyngeal Carcinoma , Nasopharyngeal Neoplasms , Radiotherapy Dosage , Radiotherapy Planning, Computer-Assisted , Radiotherapy, Intensity-Modulated , Humans , Nasopharyngeal Carcinoma/radiotherapy , Radiotherapy Planning, Computer-Assisted/methods , Radiotherapy, Intensity-Modulated/methods , Nasopharyngeal Neoplasms/radiotherapy , Organs at Risk/radiation effects , Radiometry/methods , Neural Networks, Computer
11.
Sci Rep ; 14(1): 12122, 2024 05 27.
Article En | MEDLINE | ID: mdl-38802373

Recent research has focused extensively on employing Deep Learning (DL) techniques, particularly Convolutional Neural Networks (CNN), for Speech Emotion Recognition (SER). This study addresses the burgeoning interest in leveraging DL for SER, specifically focusing on Punjabi language speakers. The paper presents a novel approach to constructing and preprocessing a labeled speech corpus using diverse social media sources. By utilizing spectrograms as the primary feature representation, the proposed algorithm effectively learns discriminative patterns for emotion recognition. The method is evaluated on a custom dataset derived from various Punjabi media sources, including films and web series. Results demonstrate that the proposed approach achieves an accuracy of 69%, surpassing traditional methods like decision trees, Naïve Bayes, and random forests, which achieved accuracies of 49%, 52%, and 61% respectively. Thus, the proposed method improves accuracy in recognizing emotions from Punjabi speech signals.


Deep Learning , Emotions , Humans , Emotions/physiology , Algorithms , Neural Networks, Computer , Speech , Bayes Theorem , Social Media , Language
12.
Sci Rep ; 14(1): 12082, 2024 05 27.
Article En | MEDLINE | ID: mdl-38802422

Deep learning neural networks are often described as black boxes, as it is difficult to trace model outputs back to model inputs due to a lack of clarity over the internal mechanisms. This is even true for those neural networks designed to emulate mechanistic models, which simply learn a mapping between the inputs and outputs of mechanistic models, ignoring the underlying processes. Using a mechanistic model studying the pharmacological interaction between opioids and naloxone as a proof-of-concept example, we demonstrated that by reorganizing the neural networks' layers to mimic the structure of the mechanistic model, it is possible to achieve better training rates and prediction accuracy relative to the previously proposed black-box neural networks, while maintaining the interpretability of the mechanistic simulations. Our framework can be used to emulate mechanistic models in a large parameter space and offers an example on the utility of increasing the interpretability of deep learning networks.


Deep Learning , Naloxone , Neural Networks, Computer , Systems Biology , Systems Biology/methods , Naloxone/pharmacology , Humans , Pharmacology/methods , Analgesics, Opioid/pharmacology , Computer Simulation
13.
Sci Rep ; 14(1): 12468, 2024 05 30.
Article En | MEDLINE | ID: mdl-38816468

Post-traumatic stress disorder (PTSD) lacks clear biomarkers in clinical practice. Language as a potential diagnostic biomarker for PTSD is investigated in this study. We analyze an original cohort of 148 individuals exposed to the November 13, 2015, terrorist attacks in Paris. The interviews, conducted 5-11 months after the event, include individuals from similar socioeconomic backgrounds exposed to the same incident, responding to identical questions and using uniform PTSD measures. Using this dataset to collect nuanced insights that might be clinically relevant, we propose a three-step interdisciplinary methodology that integrates expertise from psychiatry, linguistics, and the Natural Language Processing (NLP) community to examine the relationship between language and PTSD. The first step assesses a clinical psychiatrist's ability to diagnose PTSD using interview transcription alone. The second step uses statistical analysis and machine learning models to create language features based on psycholinguistic hypotheses and evaluate their predictive strength. The third step is the application of a hypothesis-free deep learning approach to the classification of PTSD in our cohort. Results show that the clinical psychiatrist achieved a diagnosis of PTSD with an AUC of 0.72. This is comparable to a gold standard questionnaire (Area Under Curve (AUC) ≈ 0.80). The machine learning model achieved a diagnostic AUC of 0.69. The deep learning approach achieved an AUC of 0.64. An examination of model error informs our discussion. Importantly, the study controls for confounding factors, establishes associations between language and DSM-5 subsymptoms, and integrates automated methods with qualitative analysis. This study provides a direct and methodologically robust description of the relationship between PTSD and language. Our work lays the groundwork for advancing early and accurate diagnosis and using linguistic markers to assess the effectiveness of pharmacological treatments and psychotherapies.


Deep Learning , Language , Machine Learning , Stress Disorders, Post-Traumatic , Stress Disorders, Post-Traumatic/diagnosis , Humans , Male , Female , Adult , Natural Language Processing , Biomarkers , Middle Aged
14.
BMC Cancer ; 24(1): 651, 2024 May 28.
Article En | MEDLINE | ID: mdl-38807039

OBJECTIVES: This study aims to develop an innovative, deep model for thymoma risk stratification using preoperative CT images. Current algorithms predominantly focus on radiomic features or 2D deep features and require manual tumor segmentation by radiologists, limiting their practical applicability. METHODS: The deep model was trained and tested on a dataset comprising CT images from 147 patients (82 female; mean age, 54 years ± 10) who underwent surgical resection and received subsequent pathological confirmation. The eligible participants were divided into a training cohort (117 patients) and a testing cohort (30 patients) based on the CT scan time. The model consists of two stages: 3D tumor segmentation and risk stratification. The radiomic model and deep model (2D) were constructed for comparative analysis. Model performance was evaluated through dice coefficient, area under the curve (AUC), and accuracy. RESULTS: In both the training and testing cohorts, the deep model demonstrated better performance in differentiating thymoma risk, boasting AUCs of 0.998 and 0.893 respectively. This was compared to the radiomic model (AUCs of 0.773 and 0.769) and deep model (2D) (AUCs of 0.981 and 0.760). Notably, the deep model was capable of simultaneously identifying lesions, segmenting the region of interest (ROI), and differentiating the risk of thymoma on arterial phase CT images. Its diagnostic prowess outperformed that of the baseline model. CONCLUSIONS: The deep model has the potential to serve as an innovative decision-making tool, assisting on clinical prognosis evaluation and the discernment of suitable treatments for different thymoma pathological subtypes. KEY POINTS: • This study incorporated both tumor segmentation and risk stratification. • The deep model, using clinical and 3D deep features, effectively predicted thymoma risk. • The deep model improved AUCs by 16.1pt and 17.5pt compared to radiomic model and deep model (2D) respectively.


Deep Learning , Thymoma , Thymus Neoplasms , Tomography, X-Ray Computed , Humans , Female , Thymoma/diagnostic imaging , Thymoma/pathology , Middle Aged , Male , Tomography, X-Ray Computed/methods , Risk Assessment/methods , Thymus Neoplasms/pathology , Thymus Neoplasms/diagnostic imaging , Adult , Aged , Retrospective Studies
15.
PLoS Comput Biol ; 20(5): e1012075, 2024 May.
Article En | MEDLINE | ID: mdl-38768230

Tracking body parts in behaving animals, extracting fluorescence signals from cells embedded in deforming tissue, and analyzing cell migration patterns during development all require tracking objects with partially correlated motion. As dataset sizes increase, manual tracking of objects becomes prohibitively inefficient and slow, necessitating automated and semi-automated computational tools. Unfortunately, existing methods for multiple object tracking (MOT) are either developed for specific datasets and hence do not generalize well to other datasets, or require large amounts of training data that are not readily available. This is further exacerbated when tracking fluorescent sources in moving and deforming tissues, where the lack of unique features and sparsely populated images create a challenging environment, especially for modern deep learning techniques. By leveraging technology recently developed for spatial transformer networks, we propose ZephIR, an image registration framework for semi-supervised MOT in 2D and 3D videos. ZephIR can generalize to a wide range of biological systems by incorporating adjustable parameters that encode spatial (sparsity, texture, rigidity) and temporal priors of a given data class. We demonstrate the accuracy and versatility of our approach in a variety of applications, including tracking the body parts of a behaving mouse and neurons in the brain of a freely moving C. elegans. We provide an open-source package along with a web-based graphical user interface that allows users to provide small numbers of annotations to interactively improve tracking results.


Computational Biology , Animals , Mice , Computational Biology/methods , Caenorhabditis elegans/physiology , Imaging, Three-Dimensional/methods , Image Processing, Computer-Assisted/methods , Algorithms , Deep Learning
16.
PLoS Comput Biol ; 20(5): e1012100, 2024 May.
Article En | MEDLINE | ID: mdl-38768223

The activities of most enzymes and drugs depend on interactions between proteins and small molecules. Accurate prediction of these interactions could greatly accelerate pharmaceutical and biotechnological research. Current machine learning models designed for this task have a limited ability to generalize beyond the proteins used for training. This limitation is likely due to a lack of information exchange between the protein and the small molecule during the generation of the required numerical representations. Here, we introduce ProSmith, a machine learning framework that employs a multimodal Transformer Network to simultaneously process protein amino acid sequences and small molecule strings in the same input. This approach facilitates the exchange of all relevant information between the two molecule types during the computation of their numerical representations, allowing the model to account for their structural and functional interactions. Our final model combines gradient boosting predictions based on the resulting multimodal Transformer Network with independent predictions based on separate deep learning representations of the proteins and small molecules. The resulting predictions outperform recently published state-of-the-art models for predicting protein-small molecule interactions across three diverse tasks: predicting kinase inhibitions; inferring potential substrates for enzymes; and predicting Michaelis constants KM. The Python code provided can be used to easily implement and improve machine learning predictions involving arbitrary protein-small molecule interactions.


Computational Biology , Machine Learning , Protein Kinase Inhibitors/pharmacology , Protein Kinase Inhibitors/chemistry , Substrate Specificity , Small Molecule Libraries/chemistry , Small Molecule Libraries/pharmacology , Proteins/metabolism , Proteins/chemistry , Amino Acid Sequence , Deep Learning , Protein Binding , Protein Kinases/metabolism , Protein Kinases/chemistry , Humans
17.
Nat Commun ; 15(1): 4271, 2024 May 20.
Article En | MEDLINE | ID: mdl-38769289

T Cell Receptor (TCR) antigen binding underlies a key mechanism of the adaptive immune response yet the vast diversity of TCRs and the complexity of protein interactions limits our ability to build useful low dimensional representations of TCRs. To address the current limitations in TCR analysis we develop a capacity-controlled disentangling variational autoencoder trained using a dataset of approximately 100 million TCR sequences, that we name TCR-VALID. We design TCR-VALID such that the model representations are low-dimensional, continuous, disentangled, and sufficiently informative to provide high-quality TCR sequence de novo generation. We thoroughly quantify these properties of the representations, providing a framework for future protein representation learning in low dimensions. The continuity of TCR-VALID representations allows fast and accurate TCR clustering and is benchmarked against other state-of-the-art TCR clustering tools and pre-trained language models.


Receptors, Antigen, T-Cell , Receptors, Antigen, T-Cell/immunology , Receptors, Antigen, T-Cell/metabolism , Receptors, Antigen, T-Cell/genetics , Humans , Deep Learning , Algorithms , Cluster Analysis , Computational Biology/methods , Amino Acid Sequence
18.
Bioinformatics ; 40(5)2024 May 02.
Article En | MEDLINE | ID: mdl-38775410

MOTIVATION: Accurate segmentation and recognition of C.elegans cells are critical for various biological studies, including gene expression, cell lineages, and cell fates analysis at single-cell level. However, the highly dense distribution, similar shapes, and inhomogeneous intensity profiles of whole-body cells in 3D fluorescence microscopy images make automatic cell segmentation and recognition a challenging task. Existing methods either rely on additional fiducial markers or only handle a subset of cells. Given the difficulty or expense associated with generating fiducial features in many experimental settings, a marker-free approach capable of reliably segmenting and recognizing C.elegans whole-body cells is highly desirable. RESULTS: We report a new pipeline, called automated segmentation and recognition (ASR) of cells, and applied it to 3D fluorescent microscopy images of L1-stage C.elegans with 558 whole-body cells. A novel displacement vector field based deep learning model is proposed to address the problem of reliable segmentation of highly crowded cells with blurred boundary. We then realize the cell recognition by encoding and exploiting statistical priors on cell positions and structural similarities of neighboring cells. To the best of our knowledge, this is the first method successfully applied to the segmentation and recognition of C.elegans whole-body cells. The ASR-segmentation module achieves an F1-score of 0.8956 on a dataset of 116 C.elegans image stacks with 64 728 cells (accuracy 0.9880, AJI 0.7813). Based on the segmentation results, the ASR recognition module achieved an average accuracy of 0.8879. We also show ASR's applicability to other cell types, e.g. platynereis and rat kidney cells. AVAILABILITY AND IMPLEMENTATION: The code is available at https://github.com/reaneyli/ASR.


Caenorhabditis elegans , Caenorhabditis elegans/cytology , Animals , Microscopy, Fluorescence/methods , Imaging, Three-Dimensional/methods , Image Processing, Computer-Assisted/methods , Algorithms , Deep Learning
19.
Biomed Phys Eng Express ; 10(4)2024 May 31.
Article En | MEDLINE | ID: mdl-38781934

Congenital heart defects (CHD) are one of the serious problems that arise during pregnancy. Early CHD detection reduces death rates and morbidity but is hampered by the relatively low detection rates (i.e., 60%) of current screening technology. The detection rate could be increased by supplementing ultrasound imaging with fetal ultrasound image evaluation (FUSI) using deep learning techniques. As a result, the non-invasive foetal ultrasound image has clear potential in the diagnosis of CHD and should be considered in addition to foetal echocardiography. This review paper highlights cutting-edge technologies for detecting CHD using ultrasound images, which involve pre-processing, localization, segmentation, and classification. Existing technique of preprocessing includes spatial domain filter, non-linear mean filter, transform domain filter, and denoising methods based on Convolutional Neural Network (CNN); segmentation includes thresholding-based techniques, region growing-based techniques, edge detection techniques, Artificial Neural Network (ANN) based segmentation methods, non-deep learning approaches and deep learning approaches. The paper also suggests future research directions for improving current methodologies.


Deep Learning , Heart Defects, Congenital , Neural Networks, Computer , Ultrasonography, Prenatal , Humans , Heart Defects, Congenital/diagnostic imaging , Ultrasonography, Prenatal/methods , Pregnancy , Female , Image Processing, Computer-Assisted/methods , Echocardiography/methods , Algorithms , Fetal Heart/diagnostic imaging , Fetus/diagnostic imaging
20.
Mult Scler ; 30(7): 812-819, 2024 Jun.
Article En | MEDLINE | ID: mdl-38751230

BACKGROUND: Alterations of the superficial retinal vasculature are commonly observed in multiple sclerosis (MS) and can be visualized through optical coherence tomography angiography (OCTA). OBJECTIVES: This study aimed to examine changes in the retinal vasculature during MS and to integrate findings into current concepts of the underlying pathology. METHODS: In this cross-sectional study, including 259 relapsing-remitting MS patients and 78 healthy controls, we analyzed OCTAs using deep-learning-based segmentation algorithm tools. RESULTS: We identified a loss of small-sized vessels (diameter < 10 µm) in the superficial vascular complex in all MS eyes, irrespective of their optic neuritis (ON) history. This alteration was associated with MS disease burden and appears independent of retinal ganglion cell loss. In contrast, an observed reduction of medium-sized vessels (diameter 10-20 µm) was specific to eyes with a history of ON and was closely linked to ganglion cell atrophy. CONCLUSION: These findings suggest distinct atrophy patterns in retinal vessels in patients with MS. Further studies are necessary to investigate retinal vessel alterations and their underlying pathology in MS.


Multiple Sclerosis, Relapsing-Remitting , Optic Neuritis , Retinal Vessels , Tomography, Optical Coherence , Humans , Female , Cross-Sectional Studies , Male , Adult , Retinal Vessels/pathology , Retinal Vessels/diagnostic imaging , Multiple Sclerosis, Relapsing-Remitting/pathology , Multiple Sclerosis, Relapsing-Remitting/diagnostic imaging , Middle Aged , Optic Neuritis/pathology , Optic Neuritis/diagnostic imaging , Retinal Ganglion Cells/pathology , Deep Learning , Atrophy/pathology , Cost of Illness
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