Meta-DHGNN: method for CRS-related cytokines analysis in CAR-T therapy based on meta-learning directed heterogeneous graph neural network.

Chimeric antigen receptor T-cell (CAR-T) immunotherapy, a novel approach for treating blood cancer, is associated with the production of cytokine release syndrome (CRS), which poses significant safety concerns for patients. Currently, there is limited knowledge regarding CRS-related cytokines and the intricate relationship between cytokines and cells. Therefore, it is imperative to explore a reliable and efficient computational method to identify cytokines associated with CRS. In this study, we propose Meta-DHGNN, a directed and heterogeneous graph neural network analysis method based on meta-learning. The proposed method integrates both directed and heterogeneous algorithms, while the meta-learning module effectively addresses the issue of limited data availability. This approach enables comprehensive analysis of the cytokine network and accurate prediction of CRS-related cytokines. Firstly, to tackle the challenge posed by small datasets, a pre-training phase is conducted using the meta-learning module. Consequently, the directed algorithm constructs an adjacency matrix that accurately captures potential relationships in a more realistic manner. Ultimately, the heterogeneous algorithm employs meta-photographs and multi-head attention mechanisms to enhance the realism and accuracy of predicting cytokine information associated with positive labels. Our experimental verification on the dataset demonstrates that Meta-DHGNN achieves favorable outcomes. Furthermore, based on the predicted results, we have explored the multifaceted formation mechanism of CRS in CAR-T therapy from various perspectives and identified several cytokines, such as IFNG (IFN-γ), IFNA1, IFNB1, IFNA13, IFNA2, IFNAR1, IFNAR2, IFNGR1 and IFNGR2 that have been relatively overlooked in previous studies but potentially play pivotal roles. The significance of Meta-DHGNN lies in its ability to analyze directed and heterogeneous networks in biology effectively while also facilitating CRS risk prediction in CAR-T therapy.

TMBstable: a variant caller controls performance variation across heterogeneous sequencing samples.

In cancer genomics, variant calling has advanced, but traditional mean accuracy evaluations are inadequate for biomarkers like tumor mutation burden, which vary significantly across samples, affecting immunotherapy patient selection and threshold settings. In this study, we introduce TMBstable, an innovative method that dynamically selects optimal variant calling strategies for specific genomic regions using a meta-learning framework, distinguishing it from traditional callers with uniform sample-wide strategies. The process begins with segmenting the sample into windows and extracting meta-features for clustering, followed by using a pre-trained meta-model to select suitable algorithms for each cluster, thereby addressing strategy-sample mismatches, reducing performance fluctuations and ensuring consistent performance across various samples. We evaluated TMBstable using both simulated and real non-small cell lung cancer and nasopharyngeal carcinoma samples, comparing it with advanced callers. The assessment, focusing on stability measures, such as the variance and coefficient of variation in false positive rate, false negative rate, precision and recall, involved 300 simulated and 106 real tumor samples. Benchmark results showed TMBstable's superior stability with the lowest variance and coefficient of variation across performance metrics, highlighting its effectiveness in analyzing the counting-based biomarker. The TMBstable algorithm can be accessed at https://github.com/hello-json/TMBstable for academic usage only.

In-context operator learning with data prompts for differential equation problems.

This paper introduces the paradigm of "in-context operator learning" and the corresponding model "In-Context Operator Networks" to simultaneously learn operators from the prompted data and apply it to new questions during the inference stage, without any weight update. Existing methods are limited to using a neural network to approximate a specific equation solution or a specific operator, requiring retraining when switching to a new problem with different equations. By training a single neural network as an operator learner, rather than a solution/operator approximator, we can not only get rid of retraining (even fine-tuning) the neural network for new problems but also leverage the commonalities shared across operators so that only a few examples in the prompt are needed when learning a new operator. Our numerical results show the capability of a single neural network as a few-shot operator learner for a diversified type of differential equation problems, including forward and inverse problems of ordinary differential equations, partial differential equations, and mean-field control problems, and also show that it can generalize its learning capability to operators beyond the training distribution.

KinomeMETA: meta-learning enhanced kinome-wide polypharmacology profiling.

Kinase inhibitors are crucial in cancer treatment, but drug resistance and side effects hinder the development of effective drugs. To address these challenges, it is essential to analyze the polypharmacology of kinase inhibitor and identify compound with high selectivity profile. This study presents KinomeMETA, a framework for profiling the activity of small molecule kinase inhibitors across a panel of 661 kinases. By training a meta-learner based on a graph neural network and fine-tuning it to create kinase-specific learners, KinomeMETA outperforms benchmark multi-task models and other kinase profiling models. It provides higher accuracy for understudied kinases with limited known data and broader coverage of kinase types, including important mutant kinases. Case studies on the discovery of new scaffold inhibitors for membrane-associated tyrosine- and threonine-specific cdc2-inhibitory kinase and selective inhibitors for fibroblast growth factor receptors demonstrate the role of KinomeMETA in virtual screening and kinome-wide activity profiling. Overall, KinomeMETA has the potential to accelerate kinase drug discovery by more effectively exploring the kinase polypharmacology landscape.

MetaHMEI: meta-learning for prediction of few-shot histone modifying enzyme inhibitors.

MOTIVATION: Histones are the chief protein components of chromatin, and the chemical modifications on histones crucially influence the transcriptional state of related genes. Histone modifying enzyme (HME), responsible for adding or removing the chemical labels, has emerged as a very important class of drug target, with a few HME inhibitors launched as anti-cancerous drugs and tens of molecules under clinical trials. To accelerate the drug discovery process of HME inhibitors, machine learning-based predictive models have been developed to enrich the active molecules from vast chemical space. However, the number of compounds with known activity distributed largely unbalanced among different HMEs, particularly with many targets of less than a hundred active samples. In this case, it is difficult to build effective virtual screening models directly based on machine learning. RESULTS: To this end, we propose a new Meta-learning-based Histone Modifying Enzymes Inhibitor prediction method (MetaHMEI). Our proposed MetaHMEI first uses a self-supervised pre-training approach to obtain high-quality molecular substructure embeddings from a large unlabeled chemical dataset. Then, MetaHMEI exploits a Transformer-based encoder and meta-learning framework to build a prediction model. MetaHMEI allows the effective transfer of the prior knowledge learned from HMEs with sufficient samples to HMEs with a small number of samples, so the proposed model can produce accurate predictions for HMEs with limited data. Extensive experimental results on our collected and curated HMEs datasets show that MetaHMEI is better than other methods in the case of few-shot learning. Furthermore, we applied MetaHMEI in the virtual screening process of histone JMJD3 inhibitors and successfully obtained three small molecule inhibitors, further supporting the validity of our model.

Advancing the accuracy of SARS-CoV-2 phosphorylation site detection via meta-learning approach.

The worldwide appearance of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has generated significant concern and posed a considerable challenge to global health. Phosphorylation is a common post-translational modification that affects many vital cellular functions and is closely associated with SARS-CoV-2 infection. Precise identification of phosphorylation sites could provide more in-depth insight into the processes underlying SARS-CoV-2 infection and help alleviate the continuing COVID-19 crisis. Currently, available computational tools for predicting these sites lack accuracy and effectiveness. In this study, we designed an innovative meta-learning model, Meta-Learning for Serine/Threonine Phosphorylation (MeL-STPhos), to precisely identify protein phosphorylation sites. We initially performed a comprehensive assessment of 29 unique sequence-derived features, establishing prediction models for each using 14 renowned machine learning methods, ranging from traditional classifiers to advanced deep learning algorithms. We then selected the most effective model for each feature by integrating the predicted values. Rigorous feature selection strategies were employed to identify the optimal base models and classifier(s) for each cell-specific dataset. To the best of our knowledge, this is the first study to report two cell-specific models and a generic model for phosphorylation site prediction by utilizing an extensive range of sequence-derived features and machine learning algorithms. Extensive cross-validation and independent testing revealed that MeL-STPhos surpasses existing state-of-the-art tools for phosphorylation site prediction. We also developed a publicly accessible platform at https://balalab-skku.org/MeL-STPhos. We believe that MeL-STPhos will serve as a valuable tool for accelerating the discovery of serine/threonine phosphorylation sites and elucidating their role in post-translational regulation.

CoraL: interpretable contrastive meta-learning for the prediction of cancer-associated ncRNA-encoded small peptides.

NcRNA-encoded small peptides (ncPEPs) have recently emerged as promising targets and biomarkers for cancer immunotherapy. Therefore, identifying cancer-associated ncPEPs is crucial for cancer research. In this work, we propose CoraL, a novel supervised contrastive meta-learning framework for predicting cancer-associated ncPEPs. Specifically, the proposed meta-learning strategy enables our model to learn meta-knowledge from different types of peptides and train a promising predictive model even with few labeled samples. The results show that our model is capable of making high-confidence predictions on unseen cancer biomarkers with only five samples, potentially accelerating the discovery of novel cancer biomarkers for immunotherapy. Moreover, our approach remarkably outperforms existing deep learning models on 15 cancer-associated ncPEPs datasets, demonstrating its effectiveness and robustness. Interestingly, our model exhibits outstanding performance when extended for the identification of short open reading frames derived from ncPEPs, demonstrating the strong prediction ability of CoraL at the transcriptome level. Importantly, our feature interpretation analysis discovers unique sequential patterns as the fingerprint for each cancer-associated ncPEPs, revealing the relationship among certain cancer biomarkers that are validated by relevant literature and motif comparison. Overall, we expect CoraL to be a useful tool to decipher the pathogenesis of cancer and provide valuable information for cancer research. The dataset and source code of our proposed method can be found at https://github.com/Johnsunnn/CoraL.

Meta-learning shows great potential in plant disease recognition under few available samples.

Plant diseases worsen the threat of food shortage with the growing global population, and disease recognition is the basis for the effective prevention and control of plant diseases. Deep learning has made significant breakthroughs in the field of plant disease recognition. Compared with traditional deep learning, meta-learning can still maintain more than 90% accuracy in disease recognition with small samples. However, there is no comprehensive review on the application of meta-learning in plant disease recognition. Here, we mainly summarize the functions, advantages, and limitations of meta-learning research methods and their applications for plant disease recognition with a few data scenarios. Finally, we outline several research avenues for utilizing current and future meta-learning in plant science. This review may help plant science researchers obtain faster, more accurate, and more credible solutions through deep learning with fewer labeled samples.

Regulation of reinforcement learning parameters captures long-term changes in rat behaviour.

In uncertain environments in which resources fluctuate continuously, animals must permanently decide whether to stabilise learning and exploit what they currently believe to be their best option, or instead explore potential alternatives and learn fast from new observations. While such a trade-off has been extensively studied in pretrained animals facing non-stationary decision-making tasks, it is yet unknown how they progressively tune it while learning the task structure during pretraining. Here, we compared the ability of different computational models to account for long-term changes in the behaviour of 24 rats while they learned to choose a rewarded lever in a three-armed bandit task across 24 days of pretraining. We found that the day-by-day evolution of rat performance and win-shift tendency revealed a progressive stabilisation of the way they regulated reinforcement learning parameters. We successfully captured these behavioural adaptations using a meta-learning model in which either the learning rate or the inverse temperature was controlled by the average reward rate.

Accelerating bioactive peptide discovery via mutual information-based meta-learning.

Recently, machine learning methods have been developed to identify various peptide bio-activities. However, due to the lack of experimentally validated peptides, machine learning methods cannot provide a sufficiently trained model, easily resulting in poor generalizability. Furthermore, there is no generic computational framework to predict the bioactivities of different peptides. Thus, a natural question is whether we can use limited samples to build an effective predictive model for different kinds of peptides. To address this question, we propose Mutual Information Maximization Meta-Learning (MIMML), a novel meta-learning-based predictive model for bioactive peptide discovery. Using few samples from various functional peptides, MIMML can sufficiently learn the discriminative information amongst various functions and characterize functional differences. Experimental results show excellent performance of MIMML though using far fewer training samples as compared to the state-of-the-art methods. We also decipher the latent relationships among different kinds of functions to understand what meta-model learned to improve a specific task. In summary, this study is a pioneering work in the field of functional peptide mining and provides the first-of-its-kind solution for few-sample learning problems in biological sequence analysis, accelerating the new functional peptide discovery. The source codes and datasets are available on https://github.com/TearsWaiting/MIMML.

MLNAS: Meta-learning based neural architecture search for automated generation of deep neural networks for plant disease detection tasks.

Plant diseases pose a significant threat to agricultural productivity worldwide. Convolutional neural networks (CNNs) have achieved state-of-the-art performances on several plant disease detection tasks. However, the manual development of CNN models using an exhaustive approach is a resource-intensive task. Neural Architecture Search (NAS) has emerged as an innovative paradigm that seeks to automate model generation procedures without human intervention. However, the application of NAS in plant disease detection has received limited attention. In this work, we propose a two-stage meta-learning-based neural architecture search system (ML NAS) to automate the generation of CNN models for unseen plant disease detection tasks. The first stage recommends the most suitable benchmark models for unseen plant disease detection tasks based on the prior evaluations of benchmark models on existing plant disease datasets. In the second stage, the proposed NAS operators are employed to optimize the recommended model for the target task. The experimental results showed that the MLNAS system's model outperformed state-of-the-art models on the fruit disease dataset, achieving an accuracy of 99.61%. Furthermore, the MLNAS-generated model outperformed the Progressive NAS model on the 8-class plant disease dataset, achieving an accuracy of 99.8%. Hence, the proposed MLNAS system facilitates faster model development with reduced computational costs.

Using meta-learning to recommend an appropriate time-series forecasting model.

BACKGROUND: There are various forecasting algorithms available for univariate time series, ranging from simple to sophisticated and computational. In practice, selecting the most appropriate algorithm can be difficult, because there are too many algorithms. Although expert knowledge is required to make an informed decision, sometimes it is not feasible due to the lack of such resources as time, money, and manpower. METHODS: In this study, we used coronavirus disease 2019 (COVID-19) data, including the absolute numbers of confirmed, death and recovered cases per day in 187 countries from February 20, 2020, to May 25, 2021. Two popular forecasting models, including Auto-Regressive Integrated Moving Average (ARIMA) and exponential smoothing state-space model with Trigonometric seasonality, Box-Cox transformation, ARMA errors, Trend, and Seasonal components (TBATS) were used to forecast the data. Moreover, the data were evaluated by the root mean squared error (RMSE), mean absolute error (MAE), mean absolute percentage error (MAPE), and symmetric mean absolute percentage error (SMAPE) criteria to label time series. The various characteristics of each time series based on the univariate time series structure were extracted as meta-features. After that, three machine-learning classification algorithms, including support vector machine (SVM), decision tree (DT), random forest (RF), and artificial neural network (ANN) were used as meta-learners to recommend an appropriate forecasting model. RESULTS: The finding of the study showed that the DT model had a better performance in the classification of time series. The accuracy of DT in the training and testing phases was 87.50% and 82.50%, respectively. The sensitivity of the DT algorithm in the training phase was 86.58% and its specificity was 88.46%. Moreover, the sensitivity and specificity of the DT algorithm in the testing phase were 73.33% and 88%, respectively. CONCLUSION: In general, the meta-learning approach was able to predict the appropriate forecasting model (ARIMA and TBATS) based on some time series features. Considering some characteristics of the desired COVID-19 time series, the ARIMA or TBATS forecasting model might be recommended to forecast the death, confirmed, and recovered trend cases of COVID-19 by the DT model.

Developing a novel causal inference algorithm for personalized biomedical causal graph learning using meta machine learning.

BACKGROUND: Modeling causality through graphs, referred to as causal graph learning, offers an appropriate description of the dynamics of causality. The majority of current machine learning models in clinical decision support systems only predict associations between variables, whereas causal graph learning models causality dynamics through graphs. However, building personalized causal graphs for each individual is challenging due to the limited amount of data available for each patient. METHOD: In this study, we present a new algorithmic framework using meta-learning for learning personalized causal graphs in biomedicine. Our framework extracts common patterns from multiple patient graphs and applies this information to develop individualized graphs. In multi-task causal graph learning, the proposed optimized initial guess of shared commonality enables the rapid adoption of knowledge to new tasks for efficient causal graph learning. RESULTS: Experiments on one real-world biomedical causal graph learning benchmark data and four synthetic benchmarks show that our algorithm outperformed the baseline methods. Our algorithm can better understand the underlying patterns in the data, leading to more accurate predictions of the causal graph. Specifically, we reduce the structural hamming distance by 50-75%, indicating an improvement in graph prediction accuracy. Additionally, the false discovery rate is decreased by 20-30%, demonstrating that our algorithm made fewer incorrect predictions compared to the baseline algorithms. CONCLUSION: To the best of our knowledge, this is the first study to demonstrate the effectiveness of meta-learning in personalized causal graph learning and cause inference modeling for biomedicine. In addition, the proposed algorithm can also be generalized to transnational research areas where integrated analysis is necessary for various distributions of datasets, including different clinical institutions.

Power outage prediction using data streams: An adaptive ensemble learning approach with a feature- and performance-based weighting mechanism.

A wide variety of weather conditions, from windstorms to prolonged heat events, can substantially impact power systems, posing many risks and inconveniences due to power outages. Accurately estimating the probability distribution of the number of customers without power using data about the power utility system and environmental and weather conditions can help utilities restore power more quickly and efficiently. However, the critical shortcoming of current models lies in the difficulties of handling (i) data streams and (ii) model uncertainty due to combining data from various weather events. Accordingly, this article proposes an adaptive ensemble learning algorithm for data streams, which deploys a feature- and performance-based weighting mechanism to adaptively combine outputs from multiple competitive base learners. As a proof of concept, we use a large, real data set of daily customer interruptions to develop the first adaptive all-weather outage prediction model using data streams. We benchmark several approaches to demonstrate the advantage of our approach in offering more accurate probabilistic predictions. The results show that the proposed algorithm reduces the probabilistic predictions' error of the base learners between 4% and 22% with an average of 8%, which also result in substantially more accurate point predictions. The improvement made by our algorithm is enhanced as we exchange base learners with simpler models.

Research on a Cross-Domain Few-Shot Adaptive Classification Algorithm Based on Knowledge Distillation Technology.

With the development of deep learning and sensors and sensor collection methods, computer vision inspection technology has developed rapidly. The deep-learning-based classification algorithm requires the acquisition of a model with superior generalization capabilities through the utilization of a substantial quantity of training samples. However, due to issues such as privacy, annotation costs, and sensor-captured images, how to make full use of limited samples has become a major challenge for practical training and deployment. Furthermore, when simulating models and transferring them to actual image scenarios, discrepancies often arise between the common training sets and the target domain (domain offset). Currently, meta-learning offers a promising solution for few-shot learning problems. However, the quantity of supporting set data on the target domain remains limited, leading to limited cross-domain learning effectiveness. To address this challenge, we have developed a self-distillation and mixing (SDM) method utilizing a Teacher-Student framework. This method effectively transfers knowledge from the source domain to the target domain by applying self-distillation techniques and mixed data augmentation, learning better image representations from relatively abundant datasets, and achieving fine-tuning in the target domain. In comparison with nine classical models, the experimental results demonstrate that the SDM method excels in terms of training time and accuracy. Furthermore, SDM effectively transfers knowledge from the source domain to the target domain, even with a limited number of target domain samples.

Towards Stabilized Few-Shot Object Detection with Less Forgetting via Sample Normalization.

Few-shot object detection is a challenging task aimed at recognizing novel classes and localizing with limited labeled data. Although substantial achievements have been obtained, existing methods mostly struggle with forgetting and lack stability across various few-shot training samples. In this paper, we reveal two gaps affecting meta-knowledge transfer, leading to unstable performance and forgetting in meta-learning-based frameworks. To this end, we propose sample normalization, a simple yet effective method that enhances performance stability and decreases forgetting. Additionally, we apply Z-score normalization to mitigate the hubness problem in high-dimensional feature space. Experimental results on the PASCAL VOC data set demonstrate that our approach outperforms existing methods in both accuracy and stability, achieving up to +4.4 mAP@0.5 and +5.3 mAR in a single run, with +4.8 mAP@0.5 and +5.1 mAR over 10 random experiments on average. Furthermore, our method alleviates the drop in performance of base classes. The code will be released to facilitate future research.

Enhancing the Internet of Medical Things (IoMT) Security with Meta-Learning: A Performance-Driven Approach for Ensemble Intrusion Detection Systems.

This paper investigates the application of ensemble learning techniques, specifically meta-learning, in intrusion detection systems (IDS) for the Internet of Medical Things (IoMT). It underscores the existing challenges posed by the heterogeneous and dynamic nature of IoMT environments, which necessitate adaptive, robust security solutions. By harnessing meta-learning alongside various ensemble strategies such as stacking and bagging, the paper aims to refine IDS mechanisms to effectively counter evolving cyber threats. The study proposes a performance-driven weighted meta-learning technique for dynamic assignment of voting weights to classifiers based on accuracy, loss, and confidence levels. This approach significantly enhances the intrusion detection capabilities for the IoMT by dynamically optimizing ensemble IDS models. Extensive experiments demonstrate the proposed model's superior performance in terms of accuracy, detection rate, F1 score, and false positive rate compared to existing models, particularly when analyzing various sizes of input features. The findings highlight the potential of integrating meta-learning in ensemble-based IDS to enhance the security and integrity of IoMT networks, suggesting avenues for future research to further advance IDS performance in protecting sensitive medical data and IoT infrastructures.

Few-Shot Object Detection in Remote Sensing Images via Data Clearing and Stationary Meta-Learning.

Nowadays, the focus on few-shot object detection (FSOD) is fueled by limited remote sensing data availability. In view of various challenges posed by remote sensing images (RSIs) and FSOD, we propose a meta-learning-based Balanced Few-Shot Object Detector (B-FSDet), built upon YOLOv9 (GELAN-C version). Firstly, addressing the problem of incompletely annotated objects that potentially breaks the balance of the few-shot principle, we propose a straightforward yet efficient data clearing strategy, which ensures balanced input of each category. Additionally, considering the significant variance fluctuations in output feature vectors from the support set that lead to reduced effectiveness in accurately representing object information for each class, we propose a stationary feature extraction module and corresponding stationary and fast prediction method, forming a stationary meta-learning mode. In the end, in consideration of the issue of minimal inter-class differences in RSIs, we propose inter-class discrimination support loss based on the stationary meta-learning mode to ensure the information provided for each class from the support set is balanced and easier to distinguish. Our proposed detector's performance is evaluated on the DIOR and NWPU VHR-10.v2 datasets, and comparative analysis with state-of-the-art detectors reveals promising performance.

A Novel Fault Diagnosis Method of High-Speed Train Based on Few-Shot Learning.

Ensuring the safe and stable operation of high-speed trains necessitates real-time monitoring and diagnostics of their suspension systems. While machine learning technology is widely employed for industrial equipment fault diagnosis, its effective application relies on the availability of a large dataset with annotated fault data for model training. However, in practice, the availability of informational data samples is often insufficient, with most of them being unlabeled. The challenge arises when traditional machine learning methods encounter a scarcity of training data, leading to overfitting due to limited information. To address this issue, this paper proposes a novel few-shot learning method for high-speed train fault diagnosis, incorporating sensor-perturbation injection and meta-confidence learning to improve detection accuracy. Experimental results demonstrate the superior performance of the proposed method, which introduces perturbations, compared to existing methods. The impact of perturbation effects and class numbers on fault detection is analyzed, confirming the effectiveness of our learning strategy.

Ensemble Transductive Propagation Network for Semi-Supervised Few-Shot Learning.

Few-shot learning aims to solve the difficulty in obtaining training samples, leading to high variance, high bias, and over-fitting. Recently, graph-based transductive few-shot learning approaches supplement the deficiency of label information via unlabeled data to make a joint prediction, which has become a new research hotspot. Therefore, in this paper, we propose a novel ensemble semi-supervised few-shot learning strategy via transductive network and Dempster-Shafer (D-S) evidence fusion, named ensemble transductive propagation networks (ETPN). First, we present homogeneity and heterogeneity ensemble transductive propagation networks to better use the unlabeled data, which introduce a preset weight coefficient and provide the process of iterative inferences during transductive propagation learning. Then, we combine the information entropy to improve the D-S evidence fusion method, which improves the stability of multi-model results fusion from the pre-processing of the evidence source. Third, we combine the L2 norm to improve an ensemble pruning approach to select individual learners with higher accuracy to participate in the integration of the few-shot model results. Moreover, interference sets are introduced to semi-supervised training to improve the anti-disturbance ability of the mode. Eventually, experiments indicate that the proposed approaches outperform the state-of-the-art few-shot model. The best accuracy of ETPN increases by 0.3% and 0.28% in the 5-way 5-shot, and by 3.43% and 7.6% in the 5-way 1-shot on miniImagNet and tieredImageNet, respectively.