Deep learning models have made significant advances in histological prediction tasks in recent years. However, for adaptation in clinical practice, their lack of robustness to varying conditions such as staining, scanner, hospital, and demographics is still a limiting factor: if trained on overrepresented subpopulations, models regularly struggle with less frequent patterns, leading to shortcut learning and biased predictions. Large-scale foundation models have not fully eliminated this issue. Therefore, we propose a novel approach explicitly modeling such metadata into a Metadata-guided generative Diffusion model framework (MeDi). MeDi allows for a targeted augmentation of underrepresented subpopulations with synthetic data, which balances limited training data and mitigates biases in downstream models. We experimentally show that MeDi generates high-quality histopathology images for unseen subpopulations in TCGA, boosts the overall fidelity of the generated images, and enables improvements in performance for downstream classifiers on datasets with subpopulation shifts. Our work is a proof-of-concept towards better mitigating data biases with generative models.

Spread through air spaces (STAS) represents a newly identified aggressive pattern in lung cancer, which is known to be associated with adverse prognostic factors and complex pathological features. Pathologists currently rely on time consuming manual assessments, which are highly subjective and prone to variation. This highlights the urgent need for automated and precise diag nostic solutions. 2,970 lung cancer tissue slides are comprised from multiple centers, re-diagnosed them, and constructed and publicly released three lung cancer STAS datasets: STAS CSU (hospital), STAS TCGA, and STAS CPTAC. All STAS datasets provide corresponding pathological feature diagnoses and related clinical data. To address the bias, sparse and heterogeneous nature of STAS, we propose an scale-aware multiple instance learning(SMILE) method for STAS diagnosis of lung cancer. By introducing a scale-adaptive attention mechanism, the SMILE can adaptively adjust high attention instances, reducing over-reliance on local regions and promoting consistent detection of STAS lesions. Extensive experiments show that SMILE achieved competitive diagnostic results on STAS CSU, diagnosing 251 and 319 STAS samples in CPTAC andTCGA,respectively, surpassing clinical average AUC. The 11 open baseline results are the first to be established for STAS research, laying the foundation for the future expansion, interpretability, and clinical integration of computational pathology technologies. The datasets and code are available at https://anonymous.4open.science/r/IJCAI25-1DA1.

The irregular and challenging characteristics of lung adenocarcinoma nodules in computed tomography (CT) images complicate staging diagnosis, making accurate segmentation critical for clinicians to extract detailed lesion information. In this study, we propose a segmentation model, S3TU-Net, which integrates multi-dimensional spatial connectors and a superpixel-based visual transformer. S3TU-Net is built on a multi-view CNN-Transformer hybrid architecture, incorporating superpixel algorithms, structured weighting, and spatial shifting techniques to achieve superior segmentation performance. The model leverages structured convolution blocks (DWF-Conv/D2BR-Conv) to extract multi-scale local features while mitigating overfitting. To enhance multi-scale feature fusion, we introduce the S2-MLP Link, integrating spatial shifting and attention mechanisms at the skip connections. Additionally, the residual-based superpixel visual transformer (RM-SViT) effectively merges global and local features by employing sparse correlation learning and multi-branch attention to capture long-range dependencies, with residual connections enhancing stability and computational efficiency. Experimental results on the LIDC-IDRI dataset demonstrate that S3TU-Net achieves a DSC, precision, and IoU of 89.04%, 90.73%, and 90.70%, respectively. Compared to recent methods, S3TU-Net improves DSC by 4.52% and sensitivity by 3.16%, with other metrics showing an approximate 2% increase. In addition to comparison and ablation studies, we validated the generalization ability of our model on the EPDB private dataset, achieving a DSC of 86.40%.

Deep learning has shown tremendous progress in a wide range of digital pathology and medical image classification tasks. Its integration into safe clinical decision-making support requires robust and reliable models. However, real-world data comes with diversities that often lie outside the intended source distribution. Moreover, when test samples are dramatically different, clinical decision-making is greatly affected. Quantifying predictive uncertainty in models is crucial for well-calibrated predictions and determining when (or not) to trust a model. Unfortunately, many works have overlooked the importance of predictive uncertainty estimation. This paper evaluates whether predictive uncertainty estimation adds robustness to deep learning-based diagnostic decision-making systems. We investigate the effect of various carcinoma distribution shift scenarios on predictive performance and calibration. We first systematically investigate three popular methods for improving predictive uncertainty: Monte Carlo dropout, deep ensemble, and few-shot learning on lung adenocarcinoma classification as a primary disease in whole slide images. Secondly, we compare the effectiveness of the methods in terms of performance and calibration under clinically relevant distribution shifts such as in-distribution shifts comprising primary disease sub-types and other characterization analysis data; out-of-distribution shifts comprising well-differentiated cases, different organ origin, and imaging modality shifts. While studies on uncertainty estimation exist, to our best knowledge, no rigorous large-scale benchmark compares predictive uncertainty estimation including these dataset shifts for lung carcinoma classification.

With the advent of Information technology, the Bioinformatics research field is becoming increasingly attractive to researchers and academicians. The recent development of various Bioinformatics toolkits has facilitated the rapid processing and analysis of vast quantities of biological data for human perception. Most studies focus on locating two connected diseases and making some observations to construct diverse gene regulatory interaction networks, a forerunner to general drug design for curing illness. For instance, Hypopharyngeal cancer is a disease that is associated with EGFR-mutated lung adenocarcinoma. In this study, we select EGFR-mutated lung adenocarcinoma and Hypopharyngeal cancer by finding the Lung metastases in hypopharyngeal cancer. To conduct this study, we collect Mircorarray datasets from GEO (Gene Expression Omnibus), an online database controlled by NCBI. Differentially expressed genes, common genes, and hub genes between the selected two diseases are detected for the succeeding move. Our research findings have suggested common therapeutic molecules for the selected diseases based on 10 hub genes with the highest interactions according to the degree topology method and the maximum clique centrality (MCC). Our suggested therapeutic molecules will be fruitful for patients with those two diseases simultaneously.

Lung cancer is the primary cause of cancer-related mortality, claiming approximately 1.79 million lives globally in 2020, with an estimated 2.21 million new cases diagnosed within the same period. Among these, Non-Small Cell Lung Cancer (NSCLC) is the predominant subtype, characterized by a notably bleak prognosis and low overall survival rate of approximately 25% over five years across all disease stages. However, survival outcomes vary considerably based on the stage at diagnosis and the therapeutic interventions administered. Recent advancements in artificial intelligence (AI) have revolutionized the landscape of lung cancer prognosis. AI-driven methodologies, including machine learning and deep learning algorithms, have shown promise in enhancing survival prediction accuracy by efficiently analyzing complex multi-omics data and integrating diverse clinical variables. By leveraging AI techniques, clinicians can harness comprehensive prognostic insights to tailor personalized treatment strategies, ultimately improving patient outcomes in NSCLC. Overviewing AI-driven data processing can significantly help bolster the understanding and provide better directions for using such systems.

Lung adenocarcinoma is a morphologically heterogeneous disease, characterized by five primary histologic growth patterns. The quantity of these patterns can be related to tumor behavior and has a significant impact on patient prognosis. In this work, we propose a novel machine learning pipeline capable of classifying tissue tiles into one of the five patterns or as non-tumor, with an Area Under the Receiver Operating Characteristic Curve (AUCROC) score of 0.97. Our model's strength lies in its comprehensive consideration of cellular spatial patterns, where it first generates cell maps from Hematoxylin and Eosin (H&E) whole slide images (WSIs), which are then fed into a convolutional neural network classification model. Exploiting these cell maps provides the model with robust generalizability to new data, achieving approximately 30% higher accuracy on unseen test-sets compared to current state of the art approaches. The insights derived from our model can be used to predict prognosis, enhancing patient outcomes.

Definitive cancer diagnosis and management depend upon the extraction of information from microscopy images by pathologists. These images contain complex information requiring time-consuming expert human interpretation that is prone to human bias. Supervised deep learning approaches have proven powerful for classification tasks, but they are inherently limited by the cost and quality of annotations used for training these models. To address this limitation of supervised methods, we developed Histomorphological Phenotype Learning (HPL), a fully blue{self-}supervised methodology that requires no expert labels or annotations and operates via the automatic discovery of discriminatory image features in small image tiles. Tiles are grouped into morphologically similar clusters which constitute a library of histomorphological phenotypes, revealing trajectories from benign to malignant tissue via inflammatory and reactive phenotypes. These clusters have distinct features which can be identified using orthogonal methods, linking histologic, molecular and clinical phenotypes. Applied to lung cancer tissues, we show that they align closely with patient survival, with histopathologically recognised tumor types and growth patterns, and with transcriptomic measures of immunophenotype. We then demonstrate that these properties are maintained in a multi-cancer study. These results show the clusters represent recurrent host responses and modes of tumor growth emerging under natural selection. Code, pre-trained models, learned embeddings, and documentation are available to the community at https://github.com/AdalbertoCq/Histomorphological-Phenotype-Learning

The accelerated adoption of digital pathology and advances in deep learning have enabled the development of powerful models for various pathology tasks across a diverse array of diseases and patient cohorts. However, model training is often difficult due to label scarcity in the medical domain and the model's usage is limited by the specific task and disease for which it is trained. Additionally, most models in histopathology leverage only image data, a stark contrast to how humans teach each other and reason about histopathologic entities. We introduce CONtrastive learning from Captions for Histopathology (CONCH), a visual-language foundation model developed using diverse sources of histopathology images, biomedical text, and notably over 1.17 million image-caption pairs via task-agnostic pretraining. Evaluated on a suite of 13 diverse benchmarks, CONCH can be transferred to a wide range of downstream tasks involving either or both histopathology images and text, achieving state-of-the-art performance on histology image classification, segmentation, captioning, text-to-image and image-to-text retrieval. CONCH represents a substantial leap over concurrent visual-language pretrained systems for histopathology, with the potential to directly facilitate a wide array of machine learning-based workflows requiring minimal or no further supervised fine-tuning.

Activating mutations in KRAS occur in 32% of lung adenocarcinomas (LUAD). Despite leading to aggressive disease and resistance to therapy in preclinical studies, the KRAS mutation does not predict patient outcome or response to treatment, presumably due to additional events modulating RAS pathways. To obtain a broader measure of RAS pathway activation, we developed RAS84, a transcriptional signature optimised to capture RAS oncogenic activity in LUAD. We report evidence of RAS pathway oncogenic activation in 84% of LUAD, including 65% KRAS wild-type tumours, falling into four groups characterised by coincident alteration of STK11/LKB1, TP53 or CDKN2A, suggesting that the classifications developed when considering only KRAS mutant tumours have significance in a broader cohort of patients. Critically, high RAS activity patient groups show adverse clinical outcome and reduced response to chemotherapy. Patient stratification using oncogenic RAS transcriptional activity instead of genetic alterations could ultimately assist in clinical decision-making. Mutations in RAS oncogenes and related pathways are frequent in lung cancers. Here, the authors derive a RAS gene expression signature and a machine learning classifier to predict drug response and clinical outcomes in lung adenocarcinoma and other solid tumours, with improved performance over KRAS mutations alone.