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Machine learning-guided risk stratification in elderly AML based on genomic, immunophenotypic and therapeutic profiles.

BACKGROUND: Elderly patients with acute myeloid leukemia (AML) exhibit considerable biological and clinical heterogeneity, hindering precise prognosis. Existing prognostic systems inadequately capture the complexity of elderly AML due to their reliance on data from younger cohorts and omission of key factors like immunophenotypic markers and therapeutic profiles. This study aimed to develop and internally validate a machine learning-based prognostic model specifically tailored to elderly AML patients. METHODS: A total of 156 patients were analyzed using a two-stage modeling strategy. Clinical and genomic variables were modeled first, followed by independent analysis of immunophenotypic features. Feature selection was performed using multilayer perceptron (MLP) and random forest (RF), while multivariate Cox regression was used for final model construction. Internal validation was conducted using 1000 bootstrap iterations to assess model stability and performance. RESULTS: The model demonstrated strong predictive performance, with a concordance index (C-index) of 0.702. Time-dependent area under the curve (AUC) and calibration plots confirmed accurate prediction of 1-, 3-, and 5-year overall survival. Decision curve analysis indicated favorable net benefit across a range of threshold probabilities. Key independent prognostic factors identified included TP53 mutations, high CD13 expression, and IDH2 mutations. CONCLUSION: This model provides a robust and interpretable tool for individualized risk stratification in elderly AML. By integrating genomic, immunophenotypic, and therapeutic variables, it may help optimize treatment decisions and improve outcomes for this vulnerable population. Future efforts should focus on external validation and integration of dynamic biomarkers.

Humans

Artificial Intelligence-Driven Multi-Omics Analysis Reveals Hydroxytyrosol Targeting of the TXNIP-NLRP3 Inflammasome Axis in Traumatic Brain Injury.

Traumatic brain injury (TBI) induces secondary neuroinflammation driven by oxidative stress, inflammasome activation, and immune remodeling, yet specific mechanism-guided pharmacological interventions remain limited. This study established an artificial intelligence (AI)-integrated network pharmacology and multi-omics framework to evaluate whether hydroxytyrosol (HT), an olive-derived natural polyphenol, may regulate TBI-related neuroinflammatory targets centered on the TXNIP/NLRP3 inflammasome axis. Starting from the SMILES structure of HT, potential targets were predicted using PharmMapper, SwissTargetPrediction, and the Similarity Ensemble Approach and were standardized to UniProt identifiers. TBI-associated genes were integrated from GeneCards, DisGeNET, OMIM, and the Therapeutic Target Database. The overlapping target set was analyzed using STRING-based protein-protein interaction (PPI) networks, MCODE, CytoHubba, Gene Ontology (GO), and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment. Public GEO transcriptomic datasets (GSE123831 and GSE104687) were used for cross-platform expression validation, differential expression analysis, and exploratory CIBERSORT-based immune infiltration estimation. Random forest (RF), multilayer perceptron (MLP), graph convolutional network (GCN), graph attention network (GAT), SHAP/LIME explainability analysis, LASSO inflammatory-risk scoring, and two-sample Mendelian randomization (MR) were further applied for target prioritization, immune phenotype mapping, and genetic association analysis. Seventy-three overlapping HT-TBI targets were identified. PPI and topology analyses prioritized TXNIP, NLRP3, CASP1, MAPK1, and TP53 as key hubs enriched in inflammasome activation, oxidative stress, apoptosis, and NOD-like receptor signaling. TXNIP, NLRP3, and CASP1 were consistently upregulated in both TBI transcriptomic datasets. LM22-based immune deconvolution suggested increased pro-inflammatory immune signatures and a positive TXNIP-M1 macrophage association (r&#x202f;=&#x202f;0.63, p < 0.001), which should be interpreted as a transcriptome-derived hypothesis rather than validated murine immune-cell proportions. AI-based models consistently ranked TXNIP/NLRP3 as high-contribution features under internal validation, and removal of these targets reduced model performance. A five-gene inflammatory score achieved an internally evaluated AUC of 0.87, while two-sample MR supported positive genetic associations involving TXNIP expression, TBI risk, NLRP3 and IL-1&#x3b2; expression. Collectively, these findings prioritize the TXNIP/NLRP3/CASP1 module as a computationally supported candidate mechanism through which HT may influence oxidative stress-inflammasome-immune coupling in TBI. This study provides an interpretable drug-target-pathway-phenotype framework and identifies TXNIP, NLRP3, and CASP1 as priority nodes for future experimental validation.

Artificial Intelligence

HallmarkGraph: a cancer hallmark informed graph neural network for classifying hierarchical tumor subtypes.

MOTIVATION: Accurate tumor subtype diagnosis is crucial for precision oncology, yet current methodologies face significant challenges. These include balancing model accuracy with interpretability and the high costs of generating multi-omics data in clinical settings. Moreover, there is a lack of validated models capable of classifying hierarchical tumor subtypes across a comprehensive pan-cancer cohort. RESULTS: We present a graph neural network, HallmarkGraph, the first biologically informed model developed to classify hierarchical tumor subtypes in human cancer. Inspired by cancer hallmarks, the model's architecture integrates transcriptome profiles and gene regulatory interactions to perform multi-label classification. We evaluate the model on a comprehensive pan-cancer cohort comprising 11&#xa0;476 samples from 26 primary cancers with 405 subtypes up to eight levels. The model demonstrates exceptional performance, achieving 5-fold cross-validation accuracy between 85% and 99% for tumor subtypes labeled with increasing details of genomic information. It also shows good generalizability on a validation dataset of 887 samples, assessed using three metrics that consider tumor subtypes at individual, combined, and sample levels. Benchmarking and ablation experiments show that hallmark-based embeddings slightly influence model performance, while the integrated multilayer perceptron plays a significant role in determining classifier accuracy. Additionally, we use the SHAP method to link cancer hallmarks with genes, identifying key features that influence model decisions. Our findings present a biologically informed machine learning framework capable of tracking tumor transcriptomic trajectories and distinguishing inter- and intra-tumor heterogeneity in pan-cancer. This approach holds promise for enhancing cancer diagnostics. AVAILABILITY AND IMPLEMENTATION: HallmarkGraph is accessible at https://github.com/laixn/HallmarkGraph.

Humans

Development and evaluation of a machine learning model for osteoporosis risk prediction in Korean women.

BACKGROUND: The aim of this study was to develop a machine learning (ML) model for classifying osteoporosis in Korean women based on a large-scale population cohort study. This study also aimed to assess ML model performance compared with traditional osteoporosis screening tools. Furthermore, this study aimed to examine the factors influencing the risk of osteoporosis through variable importance. METHODS: Data was collected from 4199 women aged 40-69 years in the baseline survey of the Ansan and Ansung cohort of the Korean Genome and Epidemiology Study. Osteoporosis was set as the dependent variable to develop ML classification models. Independent variables included 122 factors related to osteoporosis risk, such as socio-demographic characteristics, anthropometric parameters, lifestyle factors, reproductive factors, nutrient intakes, diet quality indices, medical history, medication history, family history, biochemical parameters, and genetic factors. The six classification models were developed using ML techniques, including decision tree, random forest, multilayer perceptron, support vector machine, light gradient boosting machine, and extreme gradient boosting (XGBoost). The six ML classification models were compared with two traditional osteoporosis screening tools, including the osteoporosis risk assessment instrument (ORAI) and the osteoporosis self-assessment tool (OST). The ML model performances were evaluated and compared using the confusion matrix and area under the curve (AUC) metrics. Variable importance was assessed using the XGBoost technique to investigate osteoporosis risk factors. RESULTS: The XGBoost model showed the highest performance out of the six ML classification models, with an accuracy of 0.705, precision of 0.664, recall of 0.830, and F1 score of 0.738. Moreover, the XGBoost model showed a higher performance on AUC than ORAI and OST. Variable importance scores were identified for 69 out of the 122 variables associated with osteoporosis risk factors. Age at menopause ranked first in variable importance. Variables of arthritis, physical activities, hypertension, education level, income level; alcohol intake, potassium intake, homeostatic model assessment for insulin resistance; energy intake, vitamin C intake, gout; and dietary inflammatory index ranked in the top 20 out of the 69 variables, using the XGBoost technique. CONCLUSIONS: This study found that an XGBoost model can be utilized to classify osteoporosis in Korean women. Age at menopause is a significant factor in osteoporosis risk, followed by arthritis, physical activities, hypertension, and education level.

Humans

Anticancer drug response prediction integrating multi-omics pathway-based difference features and multiple deep learning techniques.

Individualized prediction of cancer drug sensitivity is of vital importance in precision medicine. While numerous predictive methodologies for cancer drug response have been proposed, the precise prediction of an individual patient's response to drug and a thorough understanding of differences in drug responses among individuals continue to pose significant challenges. This study introduced a deep learning model PASO, which integrated transformer encoder, multi-scale convolutional networks and attention mechanisms to predict the sensitivity of cell lines to anticancer drugs, based on the omics data of cell lines and the SMILES representations of drug molecules. First, we use statistical methods to compute the differences in gene expression, gene mutation, and gene copy number variations between within and outside biological pathways, and utilized these pathway difference values as cell line features, combined with the drugs' SMILES chemical structure information as inputs to the model. Then the model integrates various deep learning technologies multi-scale convolutional networks and transformer encoder to extract the properties of drug molecules from different perspectives, while an attention network is devoted to learning complex interactions between the omics features of cell lines and the aforementioned properties of drug molecules. Finally, a multilayer perceptron (MLP) outputs the final predictions of drug response. Our model exhibits higher accuracy in predicting the sensitivity to anticancer drugs comparing with other methods proposed recently. It is found that PARP inhibitors, and Topoisomerase I inhibitors were particularly sensitive to SCLC when analyzing the drug response predictions for lung cancer cell lines. Additionally, the model is capable of highlighting biological pathways related to cancer and accurately capturing critical parts of the drug's chemical structure. We also validated the model's clinical utility using clinical data from The Cancer Genome Atlas. In summary, the PASO model suggests potential as a robust support in individualized cancer treatment. Our methods are implemented in Python and are freely available from GitHub (https://github.com/queryang/PASO).

Deep Learning

Sleep classification in infants based on artificial neural networks.

The study reports on the possibility of classifying sleep stages in infants using an artificial neural network. The polygraphic data from 4 babies aged 6 weeks, 6 months and 1 year recorded over 8 hours were available for classification. From each baby 22 signals were recorded, digitized and stored on an optical disc. Subsets of these signals and additional calculated parameters were used to obtain data vectors, each of which represents an interval of 30 sec. For classification, two types of neural networks were used, a Multilayer Perceptron and a Learning Vector Quantizer. The teaching input for both networks was provided by a human expert. For the 6 sleep classes in babies aged 6 months, a 65% to 80% rate of correct classification (4 babies) was obtained for the testing data not previously seen.

Cerebral Cortex

A processing strategy for automated Papanicolaou smear screening.

A multilayer processing strategy was developed for the automatic screening of conventionally prepared Papanicolaou smears. The processing stages include image segmentation, feature extraction, object classification and slide classification. Mathematical morphology functions were implemented in hardware with custom-built gate array processors for image segmentation. There were 68 features used for classifier training. In object classification we combined the evidential supports of a binary decision tree classifier and a multilayer perceptron classifier to achieve an integrated decision. In this feasibility study, 449 conventionally prepared cervical Papanicolaou smears were tested in a prototype research system between January and May 1991. The 95% confidence interval for the slide false-negative rate was 1-9%, and the 95% confidence interval for the slide sort rate was 45-55%. The estimated sort rate for clearly normal slides is within the range required for a cost-efficient screening system, and the estimated false-negative rate for premalignant and malignant smears is an improvement over published false-negative rates for human performance. Several performance improvement efforts are still under way. We expect that they will result in a vastly reduced slide false-negative rate.

Automation

Learning processes in multilayer threshold nets.

An algorithm of learning in multilayer threshold nets without feedbacks is proposed. The net is built of threshold elements with binary inputs. During a learning process each input vector chi is accompanied by a teacher's decision omega (omega epsilon(1,...,M)). The pairs (chi[n], omega[n]) appear in successive steps independently according to some unknown stationary distribution p(chi, omega). The problem of learning of a threshold net has been decomposed to a series of problems of learning of the threshold elements. The proposed learning algorithm of the threshold elements has a perceptron-like form. It was proven that a decision rule of the threshold net stabilizes after a finite number of steps. For definite classes (p(chi,omega))K of distributions p(chi, omega), an optimal decision rule stabilizes after a finite number of steps. These classes (p(chi, omega))K also contain distributions describing learning processes with perturbations.

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