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This paper proposes a novel propensity score weighting analysis. We define two sufficient and necessary conditions for a function of the covariates to be the propensity score. The first is "local balance", which ensures the conditional independence of covariates and treatment assignment across a dense grid of propensity score values. The second condition, "local calibration", guarantees that a balancing score is a propensity score. Using three-layer feed-forward neural networks, we develop a nonparametric propensity score model that satisfies these conditions, effectively circumventing the issue of model misspecification and optimizing covariate balance to minimize bias and stabilize the inverse probability weights. Our proposed method performed substantially better than existing methods in extensive numerical studies of both real and simulated benchmark datasets., Comment: Corresponding author: Chong Wu (Email: CWu18@mdanderson.org) and Liang Li (Email: LLi15@mdanderson.org)

Mediation analysis is a powerful tool for studying causal pathways between exposure, mediator, and outcome variables of interest. While classical mediation analysis using observational data often requires strong and sometimes unrealistic assumptions, such as unconfoundedness, Mendelian Randomization (MR) avoids unmeasured confounding bias by employing genetic variations as instrumental variables. We develop a novel MR framework for mediation analysis with genome-wide associate study (GWAS) summary data, and provide solid statistical guarantees. Our framework employs carefully crafted estimating equations, allowing for different sets of genetic variations to instrument the exposure and the mediator, to efficiently integrate information stored in three independent GWAS. As part of this endeavor, we demonstrate that in mediation analysis, the challenge raised by instrument selection goes beyond the well-known winner's curse issue, and therefore, addressing it requires special treatment. We then develop bias correction techniques to address the instrument selection issue and commonly encountered measurement error bias issue. Collectively, through our theoretical investigations, we show that our framework provides valid statistical inference for both direct and mediation effects with enhanced statistical efficiency compared to existing methods. We further illustrate the finite-sample performance of our approach through simulation experiments and a case study.

Background: Missing data is a common challenge in mass spectrometry-based metabolomics, which can lead to biased and incomplete analyses. The integration of whole-genome sequencing (WGS) data with metabolomics data has emerged as a promising approach to enhance the accuracy of data imputation in metabolomics studies. Method: In this study, we propose a novel method that leverages the information from WGS data and reference metabolites to impute unknown metabolites. Our approach utilizes a multi-view variational autoencoder to jointly model the burden score, polygenetic risk score (PGS), and linkage disequilibrium (LD) pruned single nucleotide polymorphisms (SNPs) for feature extraction and missing metabolomics data imputation. By learning the latent representations of both omics data, our method can effectively impute missing metabolomics values based on genomic information. Results: We evaluate the performance of our method on empirical metabolomics datasets with missing values and demonstrate its superiority compared to conventional imputation techniques. Using 35 template metabolites derived burden scores, PGS and LD-pruned SNPs, the proposed methods achieved R^2-scores > 0.01 for 71.55% of metabolites. Conclusion: The integration of WGS data in metabolomics imputation not only improves data completeness but also enhances downstream analyses, paving the way for more comprehensive and accurate investigations of metabolic pathways and disease associations. Our findings offer valuable insights into the potential benefits of utilizing WGS data for metabolomics data imputation and underscore the importance of leveraging multi-modal data integration in precision medicine research., Comment: 19 pages, 3 figures

There has been a recent emphasis on integrating physical models and deep neural networks (DNNs) for SAR target recognition, to improve performance and achieve a higher level of physical interpretability. The attributed scattering center (ASC) parameters garnered the most interest, being considered as additional input data or features for fusion in most methods. However, the performance greatly depends on the ASC optimization result, and the fusion strategy is not adaptable to different types of physical information. Meanwhile, the current evaluation scheme is inadequate to assess the model's robustness and generalizability. Thus, we propose a physics inspired hybrid attention (PIHA) mechanism and the once-for-all (OFA) evaluation protocol to address the above issues. PIHA leverages the high-level semantics of physical information to activate and guide the feature group aware of local semantics of target, so as to re-weight the feature importance based on knowledge prior. It is flexible and generally applicable to various physical models, and can be integrated into arbitrary DNNs without modifying the original architecture. The experiments involve a rigorous assessment using the proposed OFA, which entails training and validating a model on either sufficient or limited data and evaluating on multiple test sets with different data distributions. Our method outperforms other state-of-the-art approaches in 12 test scenarios with same ASC parameters. Moreover, we analyze the working mechanism of PIHA and evaluate various PIHA enabled DNNs. The experiments also show PIHA is effective for different physical information. The source code together with the adopted physical information is available at https://github.com/XAI4SAR.

In the past decade, the increased availability of genome-wide association studies summary data has popularized Mendelian Randomization (MR) for conducting causal inference. MR analyses, incorporating genetic variants as instrumental variables, are known for their robustness against reverse causation bias and unmeasured confounders. Nevertheless, classical MR analyses utilizing summary data may still produce biased causal effect estimates due to the winner's curse and pleiotropic issues. To address these two issues and establish valid causal conclusions, we propose a unified robust Mendelian Randomization framework with summary data, which systematically removes the winner's curse and screens out invalid genetic instruments with pleiotropic effects. Different from existing robust MR literature, our framework delivers valid statistical inference on the causal effect neither requiring the genetic pleiotropy effects to follow any parametric distribution nor relying on perfect instrument screening property. Under appropriate conditions, we show that our proposed estimator converges to a normal distribution and its variance can be well estimated. We demonstrate the performance of our proposed estimator through Monte Carlo simulations and two case studies. The codes implementing the procedures are available at https://github.com/ChongWuLab/CARE/.

Developments in genome-wide association studies and the increasing availability of summary genetic association data have made the application of two-sample Mendelian Randomization (MR) with summary data increasingly popular. Conventional two-sample MR methods often employ the same sample for selecting relevant genetic variants and for constructing final causal estimates. Such a practice often leads to biased causal effect estimates due to the well known "winner's curse" phenomenon. To address this fundamental challenge, we first examine its consequence on causal effect estimation both theoretically and empirically. We then propose a novel framework that systematically breaks the winner's curse, leading to unbiased association effect estimates for the selected genetic variants. Building upon the proposed framework, we introduce a novel rerandomized inverse variance weighted estimator that is consistent when selection and parameter estimation are conducted on the same sample. Under appropriate conditions, we show that the proposed RIVW estimator for the causal effect converges to a normal distribution asymptotically and its variance can be well estimated. We illustrate the finite-sample performance of our approach through Monte Carlo experiments and two empirical examples.

In biomedical science, analyzing treatment effect heterogeneity plays an essential role in assisting personalized medicine. The main goals of analyzing treatment effect heterogeneity include estimating treatment effects in clinically relevant subgroups and predicting whether a patient subpopulation might benefit from a particular treatment. Conventional approaches often evaluate the subgroup treatment effects via parametric modeling and can thus be susceptible to model mis-specifications. In this manuscript, we take a model-free semiparametric perspective and aim to efficiently evaluate the heterogeneous treatment effects of multiple subgroups simultaneously under the one-step targeted maximum-likelihood estimation (TMLE) framework. When the number of subgroups is large, we further expand this path of research by looking at a variation of the one-step TMLE that is robust to the presence of small estimated propensity scores in finite samples. From our simulations, our method demonstrates substantial finite sample improvements compared to conventional methods. In a case study, our method unveils the potential treatment effect heterogeneity of rs12916-T allele (a proxy for statin usage) in decreasing Alzheimer's disease risk., Comment: Accepted by Biometrics 2022

Sign Language (SL), as the mother tongue of the deaf community, is a special visual language that most hearing people cannot understand. In recent years, neural Sign Language Translation (SLT), as a possible way for bridging communication gap between the deaf and the hearing people, has attracted widespread academic attention. We found that the current mainstream end-to-end neural SLT models, which tries to learning language knowledge in a weakly supervised manner, could not mine enough semantic information under the condition of low data resources. Therefore, we propose to introduce additional word-level semantic knowledge of sign language linguistics to assist in improving current end-to-end neural SLT models. Concretely, we propose a novel neural SLT model with multi-modal feature fusion based on the dynamic graph, in which the cross-modal information, i.e. text and video, is first assembled as a dynamic graph according to their correlation, and then the graph is processed by a multi-modal graph encoder to generate the multi-modal embeddings for further usage in the subsequent neural translation models. To the best of our knowledge, we are the first to introduce graph neural networks, for fusing multi-modal information, into neural sign language translation models. Moreover, we conducted experiments on a publicly available popular SLT dataset RWTH-PHOENIX-Weather-2014T. and the quantitative experiments show that our method can improve the model.

Convolutional neural networks (CNNs) are usually used as a backbone to design methods in biomedical image segmentation. However, the limitation of receptive field and large number of parameters limit the performance of these methods. In this paper, we propose a graph neural network (GNN) based method named GNN-SEG for the segmentation of brain tissues. Different to conventional CNN based methods, GNN-SEG takes superpixels as basic processing units and uses GNNs to learn the structure of brain tissues. Besides, inspired by the interaction mechanism in biological vision systems, we propose two kinds of interaction modules for feature enhancement and integration. In the experiments, we compared GNN-SEG with state-of-the-art CNN based methods on four datasets of brain magnetic resonance images. The experimental results show the superiority of GNN-SEG., Comment: The original version of this paper was accepted and presented at 2022 International Joint Conference on Neural Networks (IJCNN). This version corrects the mistakes in Figs. 7 and 8

There have been increased concerns that the use of statins, one of the most commonly prescribed drugs for treating coronary artery disease, is potentially associated with the increased risk of new-onset type II diabetes (T2D). Nevertheless, to date, there is no robust evidence supporting as to whether and what kind of populations are indeed vulnerable for developing T2D after taking statins. In this case study, leveraging the biobank and electronic health record data in the Partner Health System, we introduce a new data analysis pipeline and a novel statistical methodology that address existing limitations by (i) designing a rigorous causal framework that systematically examines the causal effects of statin usage on T2D risk in observational data, (ii) uncovering which patient subgroup is most vulnerable for developing T2D after taking statins, and (iii) assessing the replicability and statistical significance of the most vulnerable subgroup via a bootstrap calibration procedure. Our proposed approach delivers asymptotically sharp confidence intervals and debiased estimate for the treatment effect of the most vulnerable subgroup in the presence of high-dimensional covariates. With our proposed approach, we find that females with high T2D genetic risk are at the highest risk of developing T2D due to statin usage., Comment: 25 pages, 2 figures, 5 tables

We firstly simulated disease dynamics by KAN (Kolmogorov-Arnold Networks) nearly 4 years ago, but the kernel functions in the edge include the exponential number of infected and discharged people and is also in line with the Kolmogorov-Arnold representation theorem, and the shared weights in the edge are the infection rate and cure rate, and used activation function by tanh at the node of edge. And this Arxiv preprint version 1 of March 2022 is an upgraded version of KAN, considering the invariant coarse-grained which calculated by residual or gradient of MSE loss. The improved KAN is PNN (Plasticity Neural Networks) or ELKAN (Edge Learning KNN), in addition to edge learning, it also considered the trimming of the edge. We not inspired by the Kolmogorov-Arnold representation theorem but inspired by the brain science. The ELKAN to explain brain, the variables correspond to different types of neurons, the learning edge can be explained by rebalance of synaptic strength and glial cells phagocytose synapses, and the kernel function means the discharge of neurons and synapses, different neurons and edges mean brain regions. Through testing by cosine, the ELKAN or ORPNN (Optimized Range PNN) is better than the KAN or CRPNN (Constant Range PNN).The ELKAN is more general to explore brain, such as mechanism of consciousness, interactions of natural frequencies in brain regions, synaptic and neuronal discharge frequencies, and data signal frequencies; mechanism of Alzheimer's disease, the Alzheimer's patients has more high frequencies in the upstream brain regions; long short-term relatively good and inferior memory which means gradient of architecture and architecture; turbulent energy flow in different brain regions, turbulence critical conditions need to be met; heart-brain of the quantum entanglement may occur between the emotions of heartbeat and the synaptic strength of brain potentials.