Despite advances in deep learning (DL) and computer vision, breast cancer (BC) detection via ultrasound remains challenging. Existing methods often focus on single tasks using complex pipelines and publicly available datasets, limiting clinical applicability. To address this, we propose BreastUS-Net-a novel architecture for hierarchical BC classification using diverse datasets. Our approach uses a dual-branch MobileNet architecture with fine-tuned and frozen layers to capture both task-specific and general features, eliminating manual feature extraction. These features are then fused to create a comprehensive representation, which is subsequently aggregated and refined. The aggregation step merges the outputs from both branches, while the refinement module reduces complexity, highlights relevant patterns, and mitigates overfitting to improve generalization. Additionally, we integrate a multihead self-attention (MHSA) block to highlight diagnostically significant regions in ultrasound images, enhancing both accuracy and robustness. Finally, the orthogonal softmax layer (OSL) boosts discriminative power by enforcing orthogonality among weight vectors, reducing parameter co-adaptation and enabling more effective optimization. We used six diverse datasets from multiple centers, including: a large Zhejiang Cancer Hospital set (2,171 images), public BUSI dataset (780 images), external test sets from Yunnan Cancer Hospital (351 images) and Sir Run Run Shaw Hospitals (365 images), fibroadenoma (FA) vs. phyllodes tumor (PT) classification, and a PT grading dataset. We use explainable AI (XAI) techniques-Grad-CAM, SHAP, and saliency maps-to enhance trust in breast ultrasound predictions. Our model achieves state-of-the-art performance, with accuracies of 94.48% on a clinical dataset and 94.23% on the BUSI dataset, highlighting its potential to improve BC diagnosis and personalized treatment.

MOTIVATION: Over the past decades, a variety of in silico methods have been developed to predict protein subcellular localization within cells. However, a common and major challenge in the design and development of such methods is how to effectively utilize the heterogeneous feature sets extracted from bioimages. In this regards, limited efforts have been undertaken. RESULTS: We propose a new two-level stacked autoencoder network (termed 2L-SAE-SM) to improve its performance by integrating the heterogeneous feature sets. In particular, in the first level of 2L-SAE-SM, each optimal heterogeneous feature set is fed to train our designed stacked autoencoder network (SAE-SM). All the trained SAE-SMs in the first level can output the decision sets based on their respective optimal heterogeneous feature sets, known as 'intermediate decision' sets. Such intermediate decision sets are then ensembled using the mean ensemble method to generate the 'intermediate feature' set for the second-level SAE-SM. Using the proposed framework, we further develop a novel predictor, referred to as PScL-2LSAESM, to characterize image-based protein subcellular localization. Extensive benchmarking experiments on the latest benchmark training and independent test datasets collected from the human protein atlas databank demonstrate the effectiveness of the proposed 2L-SAE-SM framework for the integration of heterogeneous feature sets. Moreover, performance comparison of the proposed PScL-2LSAESM with current state-of-the-art methods further illustrates that PScL-2LSAESM clearly outperforms the existing state-of-the-art methods for the task of protein subcellular localization. AVAILABILITY AND IMPLEMENTATION: https://github.com/csbio-njust-edu/PScL-2LSAESM. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

MOTIVATION: Characterization of protein subcellular localization has become an important and long-standing task in bioinformatics and computational biology, which provides valuable information for elucidating various cellular functions of proteins and guiding drug design. RESULTS: Here, we develop a novel bioimage-based computational approach, termed PScL-DDCFPred, to accurately predict protein subcellular localizations in human tissues. PScL-DDCFPred first extracts multiview image features, including global and local features, as base or pure features; next, it applies a new integrative feature selection method based on stepwise discriminant analysis and generalized discriminant analysis to identify the optimal feature sets from the extracted pure features; Finally, a classifier based on deep neural network (DNN) and deep-cascade forest (DCF) is established. Stringent 10-fold cross-validation tests on the new protein subcellular localization training dataset, constructed from the human protein atlas databank, illustrates that PScL-DDCFPred achieves a better performance than several existing state-of-the-art methods. Moreover, the independent test set further illustrates the generalization capability and superiority of PScL-DDCFPred over existing predictors. In-depth analysis shows that the excellent performance of PScL-DDCFPred can be attributed to three critical factors, namely the effective combination of the DNN and DCF models, complementarity of global and local features, and use of the optimal feature sets selected by the integrative feature selection algorithm. AVAILABILITY AND IMPLEMENTATION: https://github.com/csbio-njust-edu/PScL-DDCFPred. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

Protein subcellular localization plays a crucial role in characterizing the function of proteins and understanding various cellular processes. Therefore, accurate identification of protein subcellular location is an important yet challenging task. Numerous computational methods have been proposed to predict the subcellular location of proteins. However, most existing methods have limited capability in terms of the overall accuracy, time consumption and generalization power. To address these problems, in this study, we developed a novel computational approach based on human protein atlas (HPA) data, referred to as PScL-HDeep, for accurate and efficient image-based prediction of protein subcellular location in human tissues. We extracted different handcrafted and deep learned (by employing pretrained deep learning model) features from different viewpoints of the image. The step-wise discriminant analysis (SDA) algorithm was applied to generate the optimal feature set from each original raw feature set. To further obtain a more informative feature subset, support vector machine-based recursive feature elimination with correlation bias reduction (SVM-RFE + CBR) feature selection algorithm was applied to the integrated feature set. Finally, the classification models, namely support vector machine with radial basis function (SVM-RBF) and support vector machine with linear kernel (SVM-LNR), were learned on the final selected feature set. To evaluate the performance of the proposed method, a new gold standard benchmark training dataset was constructed from the HPA databank. PScL-HDeep achieved the maximum performance on 10-fold cross validation test on this dataset and showed a better efficacy over existing predictors. Furthermore, we also illustrated the generalization ability of the proposed method by conducting a stringent independent validation test.