Language models pre-trained on scientific literature corpora have substantially advanced scientific discovery by offering high-quality feature representations for downstream applications. However, these features are often not interpretable, and thus can reveal limited insights to domain experts. Instead of obtaining features from language models, we propose BLIAM, a literature-based data synthesis approach to directly generate training data points that are interpretable and model-agnostic to downstream applications. The key idea of BLIAM is to create prompts using existing training data and then use these prompts to synthesize new data points. BLIAM performs these two steps iteratively as new data points will define more informative prompts and new prompts will in turn synthesize more accurate data points. Notably, literature-based data augmentation might introduce data leakage since labels of test data points in downstream applications might have already been mentioned in the language model corpus. To prevent such leakage, we introduce GDSC-combo, a large-scale drug combination discovery dataset that was published after the biomedical language model was trained. We found that BLIAM substantially outperforms a non-augmented approach and manual prompting in this rigorous data split setting. BLIAM can be further used to synthesize data points for novel drugs and cell lines that were not even measured in biomedical experiments. In addition to the promising prediction performance, the data points synthesized by BLIAM are interpretable and model-agnostic, enabling in silico augmentation for in vitro experiments.
Large language models (LLMs) have recently demonstrated their potential in clinical applications, providing valuable medical knowledge and advice. For example, a large dialog LLM like ChatGPT has successfully passed part of the US medical licensing exam. However, LLMs currently have difficulty processing images, making it challenging to interpret information from medical images, which are rich in information that supports clinical decisions. On the other hand, computer-aided diagnosis (CAD) networks for medical images have seen significant success in the medical field by using advanced deep-learning algorithms to support clinical decision-making. This paper presents a method for integrating LLMs into medical-image CAD networks. The proposed framework uses LLMs to enhance the output of multiple CAD networks, such as diagnosis networks, lesion segmentation networks, and report generation networks, by summarizing and reorganizing the information presented in natural language text format. The goal is to merge the strengths of LLMs' medical domain knowledge and logical reasoning with the vision understanding capability of existing medical-image CAD models to create a more user-friendly and understandable system for patients compared to conventional CAD systems. In the future, LLM's medical knowledge can be also used to improve the performance of vision-based medical-image CAD models.
Medical image segmentation methods are generally designed as fully-supervised to guarantee model performance, which require a significant amount of expert annotated samples that are high-cost and laborious. Semi-supervised image segmentation can alleviate the problem by utilizing a large number of unlabeled images along with limited labeled images. However, learning a robust representation from numerous unlabeled images remains challenging due to potential noise in pseudo labels and insufficient class separability in feature space, which undermines the performance of current semi-supervised segmentation approaches. To address the issues above, we propose a novel semi-supervised segmentation method named as Rectified Contrastive Pseudo Supervision (RCPS), which combines a rectified pseudo supervision and voxel-level contrastive learning to improve the effectiveness of semi-supervised segmentation. Particularly, we design a novel rectification strategy for the pseudo supervision method based on uncertainty estimation and consistency regularization to reduce the noise influence in pseudo labels. Furthermore, we introduce a bidirectional voxel contrastive loss to the network to ensure intra-class consistency and inter-class contrast in feature space, which increases class separability in the segmentation. The proposed RCPS segmentation method has been validated on two public datasets and an in-house clinical dataset. Experimental results reveal that the proposed method yields better segmentation performance compared with the state-of-the-art methods in semi-supervised medical image segmentation. The source code is available at https://github.com/hsiangyuzhao/RCPS.
One-shot segmentation of brain tissues is typically a dual-model iterative learning: a registration model (reg-model) warps a carefully-labeled atlas onto unlabeled images to initialize their pseudo masks for training a segmentation model (seg-model); the seg-model revises the pseudo masks to enhance the reg-model for a better warping in the next iteration. However, there is a key weakness in such dual-model iteration that the spatial misalignment inevitably caused by the reg-model could misguide the seg-model, which makes it converge on an inferior segmentation performance eventually. In this paper, we propose a novel image-aligned style transformation to reinforce the dual-model iterative learning for robust one-shot segmentation of brain tissues. Specifically, we first utilize the reg-model to warp the atlas onto an unlabeled image, and then employ the Fourier-based amplitude exchange with perturbation to transplant the style of the unlabeled image into the aligned atlas. This allows the subsequent seg-model to learn on the aligned and style-transferred copies of the atlas instead of unlabeled images, which naturally guarantees the correct spatial correspondence of an image-mask training pair, without sacrificing the diversity of intensity patterns carried by the unlabeled images. Furthermore, we introduce a feature-aware content consistency in addition to the image-level similarity to constrain the reg-model for a promising initialization, which avoids the collapse of image-aligned style transformation in the first iteration. Experimental results on two public datasets demonstrate 1) a competitive segmentation performance of our method compared to the fully-supervised method, and 2) a superior performance over other state-of-the-art with an increase of average Dice by up to 4.67%. The source code is available at: https://github.com/JinxLv/One-shot-segmentation-via-IST.
Recent lay language generation systems have used Transformer models trained on a parallel corpus to increase health information accessibility. However, the applicability of these models is constrained by the limited size and topical breadth of available corpora. We introduce CELLS, the largest (63k pairs) and broadest-ranging (12 journals) parallel corpus for lay language generation. The abstract and the corresponding lay language summary are written by domain experts, assuring the quality of our dataset. Furthermore, qualitative evaluation of expert-authored plain language summaries has revealed background explanation as a key strategy to increase accessibility. Such explanation is challenging for neural models to generate because it goes beyond simplification by adding content absent from the source. We derive two specialized paired corpora from CELLS to address key challenges in lay language generation: generating background explanations and simplifying the original abstract. We adopt retrieval-augmented models as an intuitive fit for the task of background explanation generation, and show improvements in summary quality and simplicity while maintaining factual correctness. Taken together, this work presents the first comprehensive study of background explanation for lay language generation, paving the path for disseminating scientific knowledge to a broader audience. CELLS is publicly available at: https://github.com/LinguisticAnomalies/pls_retrieval.
Heterogeneous Information Network (HIN) is essential to study complicated networks containing multiple edge types and node types. Meta-path, a sequence of node types and edge types, is the core technique to embed HINs. Since manually curating meta-paths is time-consuming, there is a pressing need to develop automated meta-path generation approaches. Existing meta-path generation approaches cannot fully exploit the rich textual information in HINs, such as node names and edge type names. To address this problem, we propose MetaFill, a text-infilling-based approach for meta-path generation. The key idea of MetaFill is to formulate meta-path identification problem as a word sequence infilling problem, which can be advanced by Pretrained Language Models (PLMs). We observed the superior performance of MetaFill against existing meta-path generation methods and graph embedding methods that do not leverage meta-paths in both link prediction and node classification on two real-world HIN datasets. We further demonstrated how MetaFill can accurately classify edges in the zero-shot setting, where existing approaches cannot generate any meta-paths. MetaFill exploits PLMs to generate meta-paths for graph embedding, opening up new avenues for language model applications in graph analysis.
Objective For the UK Biobank standardized phenotype codes are associated with patients who have been hospitalized but are missing for many patients who have been treated exclusively in an outpatient setting. We describe a method for phenotype recognition that imputes phenotype codes for all UK Biobank participants. Materials and Methods POPDx (Population-based Objective Phenotyping by Deep Extrapolation) is a bilinear machine learning framework for simultaneously estimating the probabilities of 1,538 phenotype codes. We extracted phenotypic and health-related information of 392,246 individuals from the UK Biobank for POPDx development and evaluation. A total of 12,803 ICD-10 diagnosis codes of the patients were converted to 1,538 Phecodes as gold standard labels. The POPDx framework was evaluated and compared to other available methods on automated multi-phenotype recognition. Results POPDx can predict phenotypes that are rare or even unobserved in training. We demonstrate substantial improvement of automated multi-phenotype recognition across 22 disease categories, and its application in identifying key epidemiological features associated with each phenotype. Conclusions POPDx helps provide well-defined cohorts for downstream studies. It is a general purpose method that can be applied to other biobanks with diverse but incomplete data.
Brain network analysis for traumatic brain injury (TBI) patients is critical for its consciousness level assessment and prognosis evaluation, which requires the segmentation of certain consciousness-related brain regions. However, it is difficult to construct a TBI segmentation model as manually annotated MR scans of TBI patients are hard to collect. Data augmentation techniques can be applied to alleviate the issue of data scarcity. However, conventional data augmentation strategies such as spatial and intensity transformation are unable to mimic the deformation and lesions in traumatic brains, which limits the performance of the subsequent segmentation task. To address these issues, we propose a novel medical image inpainting model named TBI-GAN to synthesize TBI MR scans with paired brain label maps. The main strength of our TBI-GAN method is that it can generate TBI images and corresponding label maps simultaneously, which has not been achieved in the previous inpainting methods for medical images. We first generate the inpainted image under the guidance of edge information following a coarse-to-fine manner, and then the synthesized intensity image is used as the prior for label inpainting. Furthermore, we introduce a registration-based template augmentation pipeline to increase the diversity of the synthesized image pairs and enhance the capacity of data augmentation. Experimental results show that the proposed TBI-GAN method can produce sufficient synthesized TBI images with high quality and valid label maps, which can greatly improve the 2D and 3D traumatic brain segmentation performance compared with the alternatives.
We propose a novel framework for Alzheimer's disease (AD) detection using brain MRIs. The framework starts with a data augmentation method called Brain-Aware Replacements (BAR), which leverages a standard brain parcellation to replace medically-relevant 3D brain regions in an anchor MRI from a randomly picked MRI to create synthetic samples. Ground truth "hard" labels are also linearly mixed depending on the replacement ratio in order to create "soft" labels. BAR produces a great variety of realistic-looking synthetic MRIs with higher local variability compared to other mix-based methods, such as CutMix. On top of BAR, we propose using a soft-label-capable supervised contrastive loss, aiming to learn the relative similarity of representations that reflect how mixed are the synthetic MRIs using our soft labels. This way, we do not fully exhaust the entropic capacity of our hard labels, since we only use them to create soft labels and synthetic MRIs through BAR. We show that a model pre-trained using our framework can be further fine-tuned with a cross-entropy loss using the hard labels that were used to create the synthetic samples. We validated the performance of our framework in a binary AD detection task against both from-scratch supervised training and state-of-the-art self-supervised training plus fine-tuning approaches. Then we evaluated BAR's individual performance compared to another mix-based method CutMix by integrating it within our framework. We show that our framework yields superior results in both precision and recall for the AD detection task.
RNA structure determination and prediction can promote RNA-targeted drug development and engineerable synthetic elements design. But due to the intrinsic structural flexibility of RNAs, all the three mainstream structure determination methods (X-ray crystallography, NMR, and Cryo-EM) encounter challenges when resolving the RNA structures, which leads to the scarcity of the resolved RNA structures. Computational prediction approaches emerge as complementary to the experimental techniques. However, none of the \textit{de novo} approaches is based on deep learning since too few structures are available. Instead, most of them apply the time-consuming sampling-based strategies, and their performance seems to hit the plateau. In this work, we develop the first end-to-end deep learning approach, E2Efold-3D, to accurately perform the \textit{de novo} RNA structure prediction. Several novel components are proposed to overcome the data scarcity, such as a fully-differentiable end-to-end pipeline, secondary structure-assisted self-distillation, and parameter-efficient backbone formulation. Such designs are validated on the independent, non-overlapping RNA puzzle testing dataset and reach an average sub-4 \AA{} root-mean-square deviation, demonstrating its superior performance compared to state-of-the-art approaches. Interestingly, it also achieves promising results when predicting RNA complex structures, a feat that none of the previous systems could accomplish. When E2Efold-3D is coupled with the experimental techniques, the RNA structure prediction field can be greatly advanced.