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Prediction of genotoxicity of chemical compounds by statistical learning methods.

Various toxicological profiles, such as genotoxic potential, need to be studied in drug discovery processes and submitted to the drug regulatory authorities for drug safety evaluation. As part of the effort for developing low cost and efficient adverse drug reaction testing tools, several statistical learning methods have been used for developing genotoxicity prediction systems with an accuracy of up to 73.8% for genotoxic (GT+) and 92.8% for nongenotoxic (GT-) agents. These systems have been developed and tested by using less than 400 known GT+ and GT- agents, which is significantly less in number and diversity than the 860 GT+ and GT- agents known at present. There is a need to examine if a similar level of accuracy can be achieved for the more diverse set of molecules and to evaluate other statistical learning methods not yet applied to genotoxicity prediction. This work is intended for testing several statistical learning methods by using 860 GT+ and GT- agents, which include support vector machines (SVM), probabilistic neural network (PNN), k-nearest neighbor (k-NN), and C4.5 decision tree (DT). A feature selection method, recursive feature elimination, is used for selecting molecular descriptors relevant to genotoxicity study. The overall accuracies of SVM, k-NN, and PNN are comparable to and those of DT lower than the results from earlier studies, with SVM giving the highest accuracies of 77.8% for GT+ and 92.7% for GT- agents. Our study suggests that statistical learning methods, particularly SVM, k-NN, and PNN, are useful for facilitating the prediction of genotoxic potential of a diverse set of molecules.

Computational Biology↗

Identification of Immune Response-Related Proteomic Biomarkers in Moyamoya Disease Using Serum Olink Proteomics.

Moyamoya disease, a rare chronic cerebrovascular disorder, requires invasive digital subtraction angiography (DSA) for diagnosis. This study employed high-throughput proteomics to identify plasma biomarkers for Moyamoya disease diagnosis. We conducted immunopanel analysis using the Olink platform to evaluate 92 immune-related proteins in plasma samples from 88 Moyamoya disease patients and 88 healthy controls. Key proteins were identified through differential expression analysis, GO, and KEGG enrichment analysis. A diagnostic model was constructed using LASSO regression, Boruta algorithm, and machine learning models including random forest and XGBoost. Validation of these proteins was performed using GEO external data sets, followed by prediction of potential therapeutic drugs and molecular docking validation through pharmacogenomic databases. A total of 44 differentially expressed proteins were identified through the Olink immunopanel, with 12 downregulated and 32 upregulated. GO and KEGG analyses revealed significant enrichment of these proteins in innate immune responses and signaling pathways such as NF-kB and MAPK. Through LASSO, random forest, and protein under-area analysis, four potential biomarkers for Moyamoya disease (MGMT, SIT1, PRDX1, TRAF2) were identified. A diagnostic model using these proteins showed the highest AUC value with the XGBoost model. Additionally, TRAF2 and PRDX1 exhibited significant expression differences in Moyamoya disease patients within the GEO data set. Our study revealed the immune landscape of Moyamoya disease, identified four biomarkers, and established a variety of diagnostic models.

Humans↗

Diversity and complexity of HIV-1 drug resistance: a bioinformatics approach to predicting phenotype from genotype.

Drug resistance testing has been shown to be beneficial for clinical management of HIV type 1 infected patients. Whereas phenotypic assays directly measure drug resistance, the commonly used genotypic assays provide only indirect evidence of drug resistance, the major challenge being the interpretation of the sequence information. We analyzed the significance of sequence variations in the protease and reverse transcriptase genes for drug resistance and derived models that predict phenotypic resistance from genotypes. For 14 antiretroviral drugs, both genotypic and phenotypic resistance data from 471 clinical isolates were analyzed with a machine learning approach. Information profiles were obtained that quantify the statistical significance of each sequence position for drug resistance. For the different drugs, patterns of varying complexity were observed, including between one and nine sequence positions with substantial information content. Based on these information profiles, decision tree classifiers were generated to identify genotypic patterns characteristic of resistance or susceptibility to the different drugs. We obtained concise and easily interpretable models to predict drug resistance from sequence information. The prediction quality of the models was assessed in leave-one-out experiments in terms of the prediction error. We found prediction errors of 9.6-15.5% for all drugs except for zalcitabine, didanosine, and stavudine, with prediction errors between 25.4% and 32.0%. A prediction service is freely available at http://cartan.gmd.de/geno2pheno.html.

Computational Biology↗

Predicting the efficiency of UAG translational stop signal through studies of physicochemical properties of its composite mono- and dinucleotides.

In this study, we explored the problem of predicting the UAG stop-codon read-through efficiency. The reported nucleotide sequences were first converted into physicochemical property vectors before being presented to a machine learning algorithm. Two sets of physicochemical properties were applied: one for mononucleosides (in terms of steric bulk, hydrophobicity and electronics) and another for dinucleotides. To the best of our knowledge, this is the first report of how dinucleotides are converted into principle components derived from NMR chemical shift data. A few efficiency prediction models were then derived and a comparison between mononucleoside and dinucleotide-based models was shown. In the derived models, the coefficients of these property based predictors lend themselves to bio-physical interpretations, an advantage which is demonstrated in this study via a prediction model based on the steric bulk factor. Although it is quite simple, the steric bulk factor model explained well the effect of sequence variations surrounding the amber stop codon and the tRNA bearing UCCU anticodon. We further proposed new alternatives at position -1 and +4 of a UAG stop codon sequence to enhance the readthrough efficiency. This research may contribute to a better understanding of the readthrough mechanisms and may also help to study the normal translation termination process.

Codon, Terminator↗

Survival prediction for clear cell renal cell carcinoma based on deep multimodal synergistic survival network.

Objective.To propose a deep multimodal synergistic survival analysis framework (Deep Multimodal Synergistic Survival Network, DMSSN) to achieve accurate prognostic analysis for clear cell renal cell carcinoma (ccRCC).Methods.This study (DMSSN) utilized matched multimodal data from the Cancer Genome Atlas-KIRC database, including CT imaging data, whole slide images, copy number variation (CNV) features, and clinical data. Deep Canonical Correlation Analysis was employed to map heterogeneous modalities into a shared latent space. Contrastive learning was introduced to enhance semantic consistency across multimodal features, and a gating network was utilized for the adaptive fusion of multimodal information to achieve precise survival risk prediction for patients.Results.Experimental results demonstrated that DMSSN achieved a Concordance Index (C-index) of 0.8153 ± 0.0994, with a Log-rank testp-value of 1.6553×10-11. DMSSN exhibited significant performance advantages over traditional statistical methods like Log-rank-Cox (0.7055 ± 0.0670) and machine learning methods such as Random Survival Forest (RSF) (0.6836 ± 0.1048). Furthermore, in comparison with similar deep learning approaches, DMSSN outperformed late fusion strategies (0.7493 ± 0.1211) and discrete-time survival models such as DeepHit (0.7655 ± 0.1041) and Nnet-surv (0.7694 ± 0.0635). Notably, DMSSN still achieved the best predictive performance when compared to the classic deep survival model DeepSurv (0.7919 ± 0.0978) and advanced state-of-the-art multimodal fusion frameworks like Context-Aware Transformer (0.7735 ± 0.0818) and Multimodal Co-Attention Transformer (0.8102 ± 0.0972). Ablation studies showed that removing any single modality led to a decline in performance, with the largest numerical decrease occurring after removing CT imaging features (C-index decreased to 0.7327), validating the complementarity of multimodal data and the pivotal role of radiomic features in prognostic assessment. Module ablation experiments further confirmed the effectiveness of the core components.Conclusion:By effectively integrating imaging, pathology, genomic, and clinical features, the DMSSN framework demonstrates superior performance and robustness in the survival prediction of ccRCC.

Carcinoma, Renal Cell↗

Analysis of respiratory pressure-volume curves in intensive care medicine using inductive machine learning.

We present a case study of machine learning and data mining in intensive care medicine. In the study, we compared different methods of measuring pressure-volume curves in artificially ventilated patients suffering from the adult respiratory distress syndrome (ARDS). Our aim was to show that inductive machine learning can be used to gain insights into differences and similarities among these methods. We defined two tasks: the first one was to recognize the measurement method producing a given pressure-volume curve. This was defined as the task of classifying pressure-volume curves (the classes being the measurement methods). The second was to model the curves themselves, that is, to predict the volume given the pressure, the measurement method and the patient data. Clearly, this can be defined as a regression task. For these two tasks, we applied C5.0 and CUBIST, two inductive machine learning tools, respectively. Apart from medical findings regarding the characteristics of the measurement methods, we found some evidence showing the value of an abstract representation for classifying curves: normalization and high-level descriptors from curve fitting played a crucial role in obtaining reasonably accurate models. Another useful feature of algorithms for inductive machine learning is the possibility of incorporating background knowledge. In our study, the incorporation of patient data helped to improve regression results dramatically, which might open the door for the individual respiratory treatment of patients in the future.

Adult↗

A probabilistic Classifier System and its application in data mining.

The article is about a new Classifier System framework for classification tasks called BYP-CS (for BaYesian Predictive Classifier System). The proposed CS approach abandons the focus on high accuracy and addresses a well-posed Data Mining goal, namely, that of uncovering the low-uncertainty patterns of dependence that manifest often in the data. To attain this goal, BYP-CS uses a fair amount of probabilistic machinery, which brings its representation language closer to other related methods of interest in statistics and machine learning. On the practical side, the new algorithm is seen to yield stable learning of compact populations, and these still maintain a respectable amount of predictive power. Furthermore, the emerging rules self-organize in interesting ways, sometimes providing unexpected solutions to certain benchmark problems.

Algorithms↗

Multi-Omics Integration Identifies a Five-Gene Metabolic Signature With Experimental Validation in Clear Cell Renal Cell Carcinoma.

BACKGROUND: Clear cell renal cell carcinoma (ccRCC) is hallmarked by profound metabolic reprogramming; however, its intricate crosstalk with the tumor immune microenvironment (TIME) and its clinical ramifications remain inadequately elucidated. This study aims to systematically decipher the metabolic-immune interplay in ccRCC through multi-omics integration, with the goal of identifying robust prognostic biomarkers and actionable therapeutic vulnerabilities. AIMS: This study aims to systematically decipher the metabolic-immune interplay in clear cell renal cell carcinoma (ccRCC) through multi‑omics integration, and to identify robust prognostic biomarkers and actionable therapeutic vulnerabilities that can inform precision risk stratification and individualized treatment strategies. METHODS: We integrated bulk transcriptomic, genomic, and clinical data from multiple ccRCC cohorts. Differential expression and functional enrichment analyses were performed to characterize metabolic pathway alterations. Mendelian randomization (MR) was employed to infer causal relationships between metabolic disorders and ccRCC risk. A machine learning-based prognostic framework, incorporating SHAP (SHapley Additive exPlanations) for feature interpretability, was constructed and rigorously validated. TIME heterogeneity was dissected using deconvolution algorithms, while drug sensitivity, tumor mutation burden (TMB), and TIDE scores were utilized to assess therapeutic responses and immune evasion. Candidate gene function was evaluated through in vitro gain- and loss-of-function assays, with expression validated via TCGA, HPA, western blot, and qRT-PCR. RESULTS: Enrichment analysis identified coordinated dysregulation in lipid metabolism, energy homeostasis, and hypoxia response pathways. MR analysis confirmed lipid metabolism disorders as a causal risk factor for ccRCC. Our machine-learning model, centered on five core SHAP-identified features (SUCLA2, ACAT1, PC, SUCLG1, and HMGCS2), demonstrated superior predictive accuracy over conventional clinical staging. Immune profiling unveiled dichotomous TIME states: the low-risk group retained active immune surveillance, whereas the high-risk group was enriched with immunosuppressive subsets. Drug sensitivity screening pinpointed LY2109761 and carmustine as high-risk-specific candidate agents. Furthermore, TMB and TIDE analyses stratified high-risk patients displaying genomic instability and immune evasion phenotypes. Functionally, SUCLA2 knockdown significantly enhanced ccRCC cell proliferation and invasion, while its overexpression suppressed these malignant phenotypes, corroborating its tumor-suppressive role. Expression patterns of the hub genes were consistently validated across multi-level datasets and experimental assays. CONCLUSION: This study establishes a precision oncology framework for ccRCC by functionally linking metabolic biomarkers, immunophenotypes, and stratified therapeutic strategies. Importantly, we identify SUCLA2 as a potential functional tumor suppressor and a promising target for further mechanistic and translational investigation.

Humans↗

Machine learning for sub-population assessment: evaluating the C-section rate of different physician practices.

We apply machine learning to the problem of subpopulation assessment for Caesarian Section. In subpopulation assessment, we are interested in making predictions not for a single patient, but for groups of patients. Typically, in any large population, different subpopulations will have different "outcome" rates. In our example, the C-section rate of a population of 22,176 expectant mothers is 16.8%; yet, the 17 physician groups that serve this population have vastly different group C-section rates, ranging from 11% to 23%. The ultimate goal of subpopulation assessment is to determine if these variations in the observed rates can be attributed to (a) variations in intrinsic risk of the patient sub-populations (i.e. some groups contain more "high-risk C-section" patients), or (b) differences in physician practice (i.e. some groups do more C-sections). Our results indicate that although there is some variation in intrinsic risk, there is also much variation in physician practice.

Artificial Intelligence↗

Dynamics and context dependence of visual category learning.

Visual category learning by humans is observed within a paradigm of supervised learning. Mental representations for recognition are reconstructed from the observed data structures by fitting to them predicted classification data obtained from similarity-based models of recognition on the one hand and machine vision systems for image understanding on the other hand. These principles are illustrated with examples concerning the dynamics and the dependence on context of processes of category learning.

Computer Simulation↗

Machine learning approaches for cancer prognosis and diagnosis via non-coding RNA: a comprehensive review.

Non-coding RNAs (ncRNAs), once considered genomic dark matter, are now established as key regulators of gene expression with widespread roles in cellular homeostasis and disease. In cancer, ncRNA expression is frequently and systematically dysregulated, and many of these molecules circulate in stable, protected form within biofluids, offering a compelling basis for non-invasive or minimally invasive diagnostic strategies. However, their clinical translation remains substantially hindered to date due to biological complexity, technical noise, and high dimensionality inherent to ncRNA expression datasets. In this context, machine learning (ML) has emerged as a powerful analytical tool to address these challenges, enabling the identification of subtle, reproducible ncRNA signatures predictive of diverse malignancies. This review critically evaluates ML-driven frameworks for cancer diagnosis and prognosis across four ncRNA subclasses, namely miRNAs, lncRNAs, circRNAs, and piRNAs, while also acknowledging the biophysical and thermodynamic models that reinforce ncRNA bioinformatics. Despite substantial methodological progress in ML-based cancer diagnosis and prognosis, key challenges persist, including tumor biological heterogeneity, limited multicenter validation, and the lack of widely adopted standardized protocols for preprocessing, normalization, and reporting workflows. Furthermore, many current ML models lack interpretability in biological or clinical context, constraining their translational utility. By synthesizing recent advances and identifying unresolved barriers, this review charts a roadmap for developing a robust, clinically actionable ncRNA biomarker platform for cancer detection. With global cancer incidence projected to exceed 35 million annual cases by 2050, validated ncRNA-ML-driven frameworks hold potential to revolutionize early-stage detection and personalized therapeutic strategies, thereby reducing the escalating socio-economic burden of cancer worldwide.

Humans↗

CAKR: commutative algebra k-mer representations for genomics.

Despite the availability of various sequence analysis models, comparative genomic analysis remains a challenge in genomics, genetics, and phylogenetics. Commutative algebra, a fundamental tool in algebraic geometry and number theory, has rarely been used in data and biological sciences. In this study, we introduce commutative algebra k-mer representations as a nonlinear algebraic framework for analyzing genomic sequences. This representation bridges commutative algebra, algebraic topology, combinatorics, and machine learning to establish a mathematical framework for comparative genomic analysis. We evaluate its effectiveness on three tasks including genetic variant classification, phylogenetic tree reconstruction, and viral classification, typically requiring alignment-based, alignment-free, and machine-learning approaches, respectively. In this work, we show that commutative algebra k-mer representations outperform five state-of-the-art sequence analysis methods across twelve primary datasets, with two additional supplementary fragment-placement benchmarks, especially in viral classification, and maintain relatively stable predictive accuracy as dataset size increases, underscoring scalability and robustness.

Genomics↗

Computational prediction of the chromosome-damaging potential of chemicals.

We report on the generation of computer-based models for the prediction of the chromosome-damaging potential of chemicals as assessed in the in vitro chromosome aberration (CA) test. On the basis of publicly available CA-test results of more than 650 chemical substances, half of which are drug-like compounds, we generated two different computational models. The first model was realized using the (Q)SAR tool MCASE. Results obtained with this model indicate a limited performance (53%) for the assessment of a chromosome-damaging potential (sensitivity), whereas CA-test negative compounds were correctly predicted with a specificity of 75%. The low sensitivity of this model might be explained by the fact that the underlying 2D-structural descriptors only describe part of the molecular mechanism leading to the induction of chromosome aberrations, that is, direct drug-DNA interactions. The second model was constructed with a more sophisticated machine learning approach and generated a classification model based on 14 molecular descriptors, which were obtained after feature selection. The performance of this model was superior to the MCASE model, primarily because of an improved sensitivity, suggesting that the more complex molecular descriptors in combination with statistical learning approaches are better suited to model the complex nature of mechanisms leading to a positive effect in the CA-test. An analysis of misclassified pharmaceuticals by this model showed that a large part of the false-negative predicted compounds were uniquely positive in the CA-test but lacked a genotoxic potential in other mutagenicity tests of the regulatory testing battery, suggesting that biologically nonsignificant mechanisms could be responsible for the observed positive CA-test result. Since such mechanisms are not amenable to modeling approaches it is suggested that a positive prediction made by the model reflects a biologically significant genotoxic potential. An integration of the machine-learning model as a screening tool in early discovery phases of drug development is proposed.

Chromosomes↗

Screening of the key single nucleotide polymorphisms in type 2 diabetes mellitus complicated with lower extremity arterial disease by machine learning.

OBJECTIVES: Diabetic lower extremity arterial disease (LEAD) is a manifestation of diabetic lower extremity vascular complications. This study aimed to screen the key single nucleotide polymorphism (SNP) gene signature in patients with type 2 diabetes mellitus (T2DM) and LEAD. METHODS: A total of 147 patients with T2DM complicated by LEAD and 144 patients with T2DM without LEAD were enrolled for transcriptome sequencing. The Plink software was used to preprocess the data. Five machine learning methods were adopted to build the SNP diagnosis models. The receiver operating characteristic (ROC) curve was used to quantify the predicted probabilities of the model. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed using the cluster Profiler package. Finally, regression statistical analysis was used to correlate the key SNPs with clinical information and biochemical indicators. RESULTS: A total of 24 SNPs were retained and 10 SNPs were risk allele genes. Nine SNPs (rs7412, rs1800629, rs699947, rs3918242, rs668, rs1800470, rs1800449, rs1800469, and rs1024611) were identified as the key SNPs sites. GO and KEGG pathway analyses revealed that these genes are mainly enriched in fluid shear stress and atherosclerosis. Finally, rs1800449 was associated with low-density lipoprotein cholesterol (LDL-C). With high density lipoprotein cholesterol (HDL-C), related site was rs1024611. The sites associated with total cholesterol (CHOL) were rs1800449 and rs7412.The site associated with apolipoprotein B (APOB) and apolipoprotein A1 (APOA1) were rs1800470 and rs1800469. CONCLUSION: This study authenticated nine SNPs for the diagnosis of T2DM patients with LEAD, which will be of great significance in the development of diagnostic molecular biomarkers for T2DM patients.

Humans↗

Genomic Language Model for Predicting Enhancers and Their Allele-Specific Activity in the Human Genome.

Predicting and deciphering the regulatory logic of enhancers is a challenging problem, due to the intricate sequence features and lack of consistent genetic or epigenetic signatures that can accurately discriminate enhancers from other genomic regions. Recent machine-learning based methods have spotlighted the importance of extracting nucleotide composition of enhancers but failed to learn the sequence context and perform suboptimally. Motivated by advances in genomic language models, we developed DNABERT-Enhancer, a novel enhancer prediction method, by applying DNABERT pre-trained language model on the human genome. We trained two different models, using large collection of enhancers curated from the ENCODE registry of candidate cis-Regulatory Elements. The best fine-tuned model achieved 88.05% accuracy with Matthews correlation coefficient of 76% on independent set aside data. Further, we present the analysis of the predicted enhancers for all chromosomes of the human genome by comparing with the enhancer regions reported in publicly available databases. Finally, we applied DNABERT-Enhancer along with other DNABERT based regulatory genomic region prediction models to predict candidate SNPs with allele-specific enhancer and transcription factor binding activity. The genome-wide enhancer annotations and candidate loss-of-function genetic variants predicted by DNABERT-Enhancer provide valuable resources for genome interpretation in functional and clinical genomics studies.

Journal Article↗

Protein solubility: sequence based prediction and experimental verification.

MOTIVATION: Obtaining soluble proteins in sufficient concentrations is a recurring limiting factor in various experimental studies. Solubility is an individual trait of proteins which, under a given set of experimental conditions, is determined by their amino acid sequence. Accurate theoretical prediction of solubility from sequence is instrumental for setting priorities on targets in large-scale proteomics projects. RESULTS: We present a machine-learning approach called PROSO to assess the chance of a protein to be soluble upon heterologous expression in Escherichia coli based on its amino acid composition. The classification algorithm is organized as a two-layered structure in which the output of primary support vector machine (SVM) classifiers serves as input for a secondary Naive Bayes classifier. Experimental progress information from the TargetDB database as well as previously published datasets were used as the source of training data. In comparison with previously published methods our classification algorithm possesses improved discriminatory capacity characterized by the Matthews Correlation Coefficient (MCC) of 0.434 between predicted and known solubility states and the overall prediction accuracy of 72% (75 and 68% for positive and negative class, respectively). We also provide experimental verification of our predictions using solubility measurements for 31 mutational variants of two different proteins.

Amino Acid Sequence↗

A development environment for predictive modelling in foods.

Waikato Environment for Knowledge Analysis (WEKA) is a comprehensive suite of Java class libraries that implement many state-of-the-art machine learning/data mining algorithms. Non-programmers interact with the software via a user interface component called the Knowledge Explorer. Applications constructed from the WEKA class libraries can be run on any computer with a web-browsing capability, allowing users to apply machine learning techniques to their own data regardless of computer platform. This paper describes the user interface component of the WEKA system in reference to previous applications in the predictive modelling of foods.

Algorithms↗

Metabolism pathway-based subtyping in pancreatic adenocarcinoma: an integrated study by bulk RNA-sequence and machine learning algorithms.

BACKGROUND: Pancreatic adenocarcinoma (PAAD) is highly aggressive, and its tumor microenvironment has significant metabolic and immune microenvironment complexity and genomic instability. In this study, by integrating the metabolic pathway activity score and clinical data, we constructed a novel risk assessment model to reveal the unique biological behavior and clinical significance behind different PAAD subtypes. METHODS: In this study, the transcriptome and clinical data of TCGA and GSE57495 databases were integrated to explore the interaction between metabolic pathways. Based on unsupervised clustering analysis of pathway activity and survival prognosis, patients with PAAD were classified into metabolic subtypes with significant prognostic differences. Subsequently, we assessed the heterogeneity of these subtypes in terms of clinical outcomes, genomic characteristics, and immune microenvironment composition. Based on the differentially expressed genes (DEGs) among metabolic subtypes, a clinical prognostic risk model and nomogram were constructed, which were double-validated by GSE57495-independent cohort and GSE57495 + TCGA-PAAD combined cohort. Finally, the correlations between risk scores (RSs) and signaling pathway activity and tumor immune microenvironment characteristics were evaluated. RESULTS: Based on metabolic pathway correlation and prognostic information, 240 patients in the TCGA-PAAD and GSE57495 datasets were divided into three subgroups. There were significant differences between subgroups in gene expression, pathway activity, clinical prognosis, and immune infiltration characteristics among the subtypes. Using machine learning algorithms, an RS model was constructed from DEGs among the subgroups, with the random forest method showing the best performance. A nomogram integrating the RS and clinical indicators demonstrated excellent predictive accuracy for 1-, 3-, and 5-year survival rates, confirming the RS as an independent prognostic factor. High- and low-risk groups exhibited significant differences in immune infiltration, pathway activity, and gene mutations. Drug sensitivity analysis showed that the high-risk group was more sensitive to AZD6244, ABT737, and other drugs. CONCLUSION: This study stratified patients with PAAD into three subgroups based on metabolic pathways and prognostic information, revealing significant differences in clinical outcomes, immune characteristics, and genetic mutations. The robust RS model developed from these findings demonstrated strong predictive power for patient survival and identified promising therapeutic strategies, providing valuable insights for advancing precision medicine in PAAD.

immune microenvironment↗