Predictive biomarkers of treatment response are lacking for metastatic clear cell renal cell carcinoma (ccRCC), a tumor type that is treated with angiogenesis inhibitors, immune checkpoint inhibitors, mTOR inhibitors and a HIF2 inhibitor. The Angioscore, an RNA-based quantification of angiogenesis, is arguably the best candidate to predict anti-angiogenic (AA) response. However, the clinical adoption of transcriptomic assays faces several challenges including standardization, time delay, and high cost. Further, ccRCC tumors are highly heterogenous, and sampling multiple areas for sequencing is impractical. Here we present a novel deep learning (DL) approach to predict the Angioscore from ubiquitous histopathology slides. To overcome the lack of interpretability, one of the biggest limitations of typical DL models, our model produces a visual vascular network which is the basis of the model's prediction. To test its reliability, we applied this model to multiple cohorts including a clinical trial dataset. Our model accurately predicts the RNA-based Angioscore on multiple independent cohorts (spearman correlations of 0.77 and 0.73). Further, the predictions help unravel meaningful biology such as association of angiogenesis with grade, stage, and driver mutation status. Finally, we find our model can predict response to AA therapy, in both a real-world cohort and the IMmotion150 clinical trial. The predictive power of our model vastly exceeds that of CD31, a marker of vasculature, and nearly rivals the performance (c-index 0.66 vs 0.67) of the ground truth RNA-based Angioscore at a fraction of the cost. By providing a robust yet interpretable prediction of the Angioscore from histopathology slides alone, our approach offers insights into angiogenesis biology and AA treatment response.
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ACM/IEEE第23屆模型驅動工程語言和系統國際會議，是模型驅動軟件和系統工程的首要會議系列，由ACM-SIGSOFT和IEEE-TCSE支持組織。自1998年以來，模型涵蓋了建模的各個方面，從語言和方法到工具和應用程序。模特的參加者來自不同的背景，包括研究人員、學者、工程師和工業專業人士。MODELS 2019是一個論壇，參與者可以圍繞建模和模型驅動的軟件和系統交流前沿研究成果和創新實踐經驗。今年的版本將為建模社區提供進一步推進建模基礎的機會，并在網絡物理系統、嵌入式系統、社會技術系統、云計算、大數據、機器學習、安全、開源等新興領域提出建模的創新應用以及可持續性。
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This research explores neural network-based numerical approximation of two-dimensional convection- dominated singularly perturbed problems on square, circular, and elliptic domains. Singularly perturbed boundary value problems pose significant challenges due to sharp boundary layers in their solutions. Additionally, the characteristic points of these domains give rise to degenerate boundary layer problems. The stiffness of these problems, caused by sharp singular layers, can lead to substantial computational errors if not properly addressed. Conventional neural network-based approaches often fail to capture these sharp transitions accurately, highlighting a critical flaw in machine learning methods. To address these issues, we conduct a thorough boundary layer analysis to enhance our understanding of sharp transitions within the boundary layers, guiding the application of numerical methods. Specifically, we employ physics-informed neural networks (PINNs) to better handle these boundary layer problems. However, PINNs may struggle with rapidly varying singularly perturbed solutions in small domain regions, leading to inaccurate or unstable results. To overcome this limitation, we introduce a semi-analytic method that augments PINNs with singular layers or corrector functions. Our numerical experiments demonstrate significant improvements in both accuracy and stability, showcasing the effectiveness of our proposed approach.
Multi-modal medical images provide complementary soft-tissue characteristics that aid in the screening and diagnosis of diseases. However, limited scanning time, image corruption and various imaging protocols often result in incomplete multi-modal images, thus limiting the usage of multi-modal data for clinical purposes. To address this issue, in this paper, we propose a novel unified multi-modal image synthesis method for missing modality imputation. Our method overall takes a generative adversarial architecture, which aims to synthesize missing modalities from any combination of available ones with a single model. To this end, we specifically design a Commonality- and Discrepancy-Sensitive Encoder for the generator to exploit both modality-invariant and specific information contained in input modalities. The incorporation of both types of information facilitates the generation of images with consistent anatomy and realistic details of the desired distribution. Besides, we propose a Dynamic Feature Unification Module to integrate information from a varying number of available modalities, which enables the network to be robust to random missing modalities. The module performs both hard integration and soft integration, ensuring the effectiveness of feature combination while avoiding information loss. Verified on two public multi-modal magnetic resonance datasets, the proposed method is effective in handling various synthesis tasks and shows superior performance compared to previous methods.
Important applications of advancements in machine learning, are in the area of healthcare, more so for neurological disorder detection. A crucial step towards understanding the neurological status, is to estimate the brain age using structural MRI volumes, in order to measure its deviation from chronological age. Factors that contribute to brain age are best captured using a data-driven approach, such as deep learning. However, it places a huge demand on the availability of diverse datasets. In this work, we propose a robust brain age estimation paradigm that utilizes a 3D CNN model, by-passing the need for model-retraining across datasets. The proposed model consists of seven 3D CNN layers, with a shared spatial attention layer incorporated at each CNN layer followed by five dense layers. The novelty of the proposed method lies in the idea of spatial attention module, with shared weights across the CNN layers. This weight sharing ensures directed attention to specific brain regions, for localizing age-related features within the data, lending robustness. The proposed model, trained on ADNI dataset comprising 516 T1 weighted MRI volumes of healthy subjects, resulted in Mean Absolute Error (MAE) of 1.662 years, which is an improvement of 1.688 years over the state-of-the-art (SOTA) model, based on disjoint test samples from the same repository. To illustrate generalizability, the same pipeline was utilized on volumes from a publicly available source called OASIS3. From OASIS3, MRI volumes 890 healthy subjects were utilized resulting in MAE of 2.265 years. Due to diversity in acquisitions across multiple sites, races and genetic factors, traditional CNN models are not guaranteed to prioritize brain regions crucial for age estimation. In contrast, the proposed weight-shared spatial attention module, directs attention on specific regions, required for the estimation.
The discrete nature of transmitted symbols poses challenges for achieving optimal detection in multiple-input multiple-output (MIMO) systems associated with a large number of antennas. Recently, the combination of two powerful machine learning methods, Markov chain Monte Carlo (MCMC) sampling and gradient descent, has emerged as a highly efficient solution to address this issue. However, existing gradient-based MCMC detectors are heuristically designed and thus are theoretically untenable. To bridge this gap, we introduce a novel sampling algorithm tailored for discrete spaces. This algorithm leverages gradients from the underlying continuous spaces for acceleration while maintaining the validity of probabilistic sampling. We prove the convergence of this method and also analyze its convergence rate using both MCMC theory and empirical diagnostics. On this basis, we develop a MIMO detector that precisely samples from the target discrete distribution and generates posterior Bayesian estimates using these samples, whose performance is thereby theoretically guaranteed. Furthermore, our proposed detector is highly parallelizable and scalable to large MIMO dimensions, positioning it as a compelling candidate for next-generation wireless networks. Simulation results show that our detector achieves near-optimal performance, significantly outperforms state-of-the-art baselines, and showcases resilience to various system setups.
Human body parsing remains a challenging problem in natural scenes due to multi-instance and inter-part semantic confusions as well as occlusions. This paper proposes a novel approach to decomposing multiple human bodies into semantic part regions in unconstrained environments. Specifically we propose a convolutional neural network (CNN) architecture which comprises of novel semantic and contour attention mechanisms across feature hierarchy to resolve the semantic ambiguities and boundary localization issues related to semantic body parsing. We further propose to encode estimated pose as higher-level contextual information which is combined with local semantic cues in a novel graphical model in a principled manner. In this proposed model, the lower-level semantic cues can be recursively updated by propagating higher-level contextual information from estimated pose and vice versa across the graph, so as to alleviate erroneous pose information and pixel level predictions. We further propose an optimization technique to efficiently derive the solutions. Our proposed method achieves the state-of-art results on the challenging Pascal Person-Part dataset.
Blood vessel networks, represented as 3D graphs, help predict disease biomarkers, simulate blood flow, and aid in synthetic image generation, relevant in both clinical and pre-clinical settings. However, generating realistic vessel graphs that correspond to an anatomy of interest is challenging. Previous methods aimed at generating vessel trees mostly in an autoregressive style and could not be applied to vessel graphs with cycles such as capillaries or specific anatomical structures such as the Circle of Willis. Addressing this gap, we introduce the first application of \textit{denoising diffusion models} in 3D vessel graph generation. Our contributions include a novel, two-stage generation method that sequentially denoises node coordinates and edges. We experiment with two real-world vessel datasets, consisting of microscopic capillaries and major cerebral vessels, and demonstrate the generalizability of our method for producing diverse, novel, and anatomically plausible vessel graphs.
The investigation of tumor invasion and metastasis dynamics is crucial for advancements in cancer biology and treatment. Many mathematical models have been developed to study the invasion of host tissue by tumor cells. In this paper, we develop a novel stochastic interacting particle-field (SIPF) algorithm that accurately simulates the cancer cell invasion process within the haptotaxis advection-diffusion (HAD) system. Our approach approximates solutions using empirical measures of particle interactions, combined with a smoother field variable - the extracellular matrix concentration (ECM) - computed by the spectral method. We derive a one-step time recursion for both the positions of stochastic particles and the field variable using the implicit Euler discretization, which is based on the explicit Green's function of an elliptic operator characterized by the Laplacian minus a positive constant. Our numerical experiments demonstrate the superior performance of the proposed algorithm, especially in computing cancer cell growth with thin free boundaries in three-dimensional (3D) space. Numerical results show that the SIPF algorithm is mesh-free, self-adaptive, and low-cost. Moreover, it is more accurate and efficient than traditional numerical techniques such as the finite difference method (FDM) and spectral methods.
Complex biological networks, comprising metabolic reactions, gene interactions, and protein interactions, often exhibit scale-free characteristics with power-law degree distributions. However, empirical studies have revealed discrepancies between observed biological network data and ideal power-law fits, highlighting the need for improved modeling approaches. To address this challenge, we propose a novel family of distributions, building upon the baseline Burr distribution. Specifically, we introduce the compounded Burr (CBurr) distribution, derived from a continuous probability distribution family, enabling flexible and efficient modeling of node degree distributions in biological networks. This study comprehensively investigates the general properties of the CBurr distribution, focusing on parameter estimation using the maximum likelihood method. Subsequently, we apply the CBurr distribution model to large-scale biological network data, aiming to evaluate its efficacy in fitting the entire range of node degree distributions, surpassing conventional power-law distributions and other benchmarks. Through extensive data analysis and graphical illustrations, we demonstrate that the CBurr distribution exhibits superior modeling capabilities compared to traditional power-law distributions. This novel distribution model holds great promise for accurately capturing the complex nature of biological networks and advancing our understanding of their underlying mechanisms.
This study examines the effect of prompt engineering on the performance of Large Language Models (LLMs) in clinical note generation. We introduce an Automatic Prompt Optimization (APO) framework to refine initial prompts and compare the outputs of medical experts, non-medical experts, and APO-enhanced GPT3.5 and GPT4. Results highlight GPT4 APO's superior performance in standardizing prompt quality across clinical note sections. A human-in-the-loop approach shows that experts maintain content quality post-APO, with a preference for their own modifications, suggesting the value of expert customization. We recommend a two-phase optimization process, leveraging APO-GPT4 for consistency and expert input for personalization.
Sensing is anticipated to have wider extensions in communication systems with the boom of non-terrestrial networks (NTNs) during the past years. In this paper, we study a bistatic sensing system by maximizing the signal-to-interference-plus-noise ration (SINR) from the target aircraft in the space-air-ground integrated network (SAGIN). We formulate a joint optimization problem for the transmit beamforming of low-earth orbit (LEO) satellite and the receive filtering of ground base station. To tackle this problem, we decompose the original problem into two sub-problems and use the alternating optimization to solve them iteratively. Using techniques of fractional programming and generalized Rayleigh quotient, the closed-form solution for each sub-problem is returned. Simulation results show that the proposed algorithm has good convergence performance.Moreover, the optimization of receive filtering dominates the optimality, especially when the satellite altitude becomes higher, which provides valuable network design insights.
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