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Molecular testing of tumor samples for targetable biomarkers is restricted by a lack of standardization, turnaround-time, cost, and tissue availability across cancer types. Additionally, targetable alterations of low prevalence may not be tested in routine workflows. Algorithms that predict DNA alterations from routinely generated hematoxylin and eosin (H&E)-stained images could prioritize samples for confirmatory molecular testing. Costs and the necessity of a large number of samples containing mutations limit approaches that train individual algorithms for each alteration. In this work, models were trained for simultaneous prediction of multiple DNA alterations from H&E images using a multi-task approach. Compared to biomarker-specific models, this approach performed better on average, with pronounced gains for rare mutations. The models reasonably generalized to independent temporal-holdout, externally-stained, and multi-site TCGA test sets. Additionally, whole slide image embeddings derived using multi-task models demonstrated strong performance in downstream tasks that were not a part of training. Overall, this is a promising approach to develop clinically useful algorithms that provide multiple actionable predictions from a single slide.

Instance-level image classification tasks have traditionally relied on single-instance labels to train models, e.g., few-shot learning and transfer learning. However, set-level coarse-grained labels that capture relationships among instances can provide richer information in real-world scenarios. In this paper, we present a novel approach to enhance instance-level image classification by leveraging set-level labels. We provide a theoretical analysis of the proposed method, including recognition conditions for fast excess risk rate, shedding light on the theoretical foundations of our approach. We conducted experiments on two distinct categories of datasets: natural image datasets and histopathology image datasets. Our experimental results demonstrate the effectiveness of our approach, showcasing improved classification performance compared to traditional single-instance label-based methods. Notably, our algorithm achieves 13% improvement in classification accuracy compared to the strongest baseline on the histopathology image classification benchmarks. Importantly, our experimental findings align with the theoretical analysis, reinforcing the robustness and reliability of our proposed method. This work bridges the gap between instance-level and set-level image classification, offering a promising avenue for advancing the capabilities of image classification models with set-level coarse-grained labels.

Digging out the latent information from large-scale incomplete matrices is a key issue with challenges. The Latent Factor Analysis (LFA) model has been investigated in depth to an alyze the latent information. Recently, Swarm Intelligence-related LFA models have been proposed and adopted widely to improve the optimization process of LFA with high efficiency, i.e., the Particle Swarm Optimization (PSO)-LFA model. However, the hyper-parameters of the PSO-LFA model have to tune manually, which is inconvenient for widely adoption and limits the learning rate as a fixed value. To address this issue, we propose an Adam-enhanced Hierarchical PSO-LFA model, which refines the latent factors with a sequential Adam-adjusting hyper-parameters PSO algorithm. First, we design the Adam incremental vector for a particle and construct the Adam-enhanced evolution process for particles. Second, we refine all the latent factors of the target matrix sequentially with our proposed Adam-enhanced PSO's process. The experimental results on four real datasets demonstrate that our proposed model achieves higher prediction accuracy with its peers.

High-Dimensional and Incomplete matrices, which usually contain a large amount of valuable latent information, can be well represented by a Latent Factor Analysis model. The performance of an LFA model heavily rely on its optimization process. Thereby, some prior studies employ the Particle Swarm Optimization to enhance an LFA model's optimization process. However, the particles within the swarm follow the static evolution paths and only share the global best information, which limits the particles' searching area to cause sub-optimum issue. To address this issue, this paper proposes a Dynamic-neighbor-cooperated Hierarchical PSO-enhanced LFA model with two-fold main ideas. First is the neighbor-cooperated strategy, which enhances the randomly chosen neighbor's velocity for particles' evolution. Second is the dynamic hyper-parameter tunning. Extensive experiments on two benchmark datasets are conducted to evaluate the proposed DHPL model. The results substantiate that DHPL achieves a higher accuracy without hyper-parameters tunning than the existing PSO-incorporated LFA models in representing an HDI matrix.

Active learning has demonstrated data efficiency in many fields. Existing active learning algorithms, especially in the context of batch-mode deep Bayesian active models, rely heavily on the quality of uncertainty estimations of the model, and are often challenging to scale to large batches. In this paper, we propose Batch-BALanCe, a scalable batch-mode active learning algorithm, which combines insights from decision-theoretic active learning, combinatorial information measure, and diversity sampling. At its core, Batch-BALanCe relies on a novel decision-theoretic acquisition function that facilitates differentiation among different equivalence classes. Intuitively, each equivalence class consists of hypotheses (e.g., posterior samples of deep neural networks) with similar predictions, and Batch-BALanCe adaptively adjusts the size of the equivalence classes as learning progresses. To scale up the computation of queries to large batches, we further propose an efficient batch-mode acquisition procedure, which aims to maximize a novel information measure defined through the acquisition function. We show that our algorithm can effectively handle realistic multi-class classification tasks, and achieves compelling performance on several benchmark datasets for active learning under both low- and large-batch regimes. Reference code is released at https://github.com/zhangrenyuuchicago/BALanCe.

Recently exciting progress has been made on protein contact prediction, but the predicted contacts for proteins without many sequence homologs is still of low quality and not very useful for de novo structure prediction. This paper presents a new deep learning method that predicts contacts by integrating both evolutionary coupling (EC) and sequence conservation information through an ultra-deep neural network formed by two deep residual networks. This deep neural network allows us to model very complex sequence-contact relationship as well as long-range inter-contact correlation. Our method greatly outperforms existing contact prediction methods and leads to much more accurate contact-assisted protein folding. Tested on three datasets of 579 proteins, the average top L long-range prediction accuracy obtained our method, the representative EC method CCMpred and the CASP11 winner MetaPSICOV is 0.47, 0.21 and 0.30, respectively; the average top L/10 long-range accuracy of our method, CCMpred and MetaPSICOV is 0.77, 0.47 and 0.59, respectively. Ab initio folding using our predicted contacts as restraints can yield correct folds (i.e., TMscore>0.6) for 203 test proteins, while that using MetaPSICOV- and CCMpred-predicted contacts can do so for only 79 and 62 proteins, respectively. Further, our contact-assisted models have much better quality than template-based models. Using our predicted contacts as restraints, we can (ab initio) fold 208 of the 398 membrane proteins with TMscore>0.5. By contrast, when the training proteins of our method are used as templates, homology modeling can only do so for 10 of them. One interesting finding is that even if we do not train our prediction models with any membrane proteins, our method works very well on membrane protein prediction. Finally, in recent blind CAMEO benchmark our method successfully folded 5 test proteins with a novel fold.