Statistical testing on generative AI anomaly detection tools in Alzheimer's Disease diagnosis

Alzheimer's Disease is challenging to diagnose due to our limited understanding of its mechanism and large heterogeneity among patients. Neurodegeneration is studied widely as a biomarker for clinical diagnosis, which can be measured from time series MRI progression. On the other hand, generative AI has shown promise in anomaly detection in medical imaging and used for tasks including tumor detection. However, testing the reliability of such data-driven methods is non-trivial due to the issue of double-dipping in hypothesis testing. In this work, we propose to solve this issue with selective inference and develop a reliable generative AI method for Alzheimer's prediction. We show that compared to traditional statistical methods with highly inflated p-values, selective inference successfully controls the false discovery rate under the desired alpha level while retaining statistical power. In practice, our pipeline could assist clinicians in Alzheimer's diagnosis and early intervention.

Statistical Test for Data Analysis Pipeline by Selective Inference

A data analysis pipeline is a structured sequence of processing steps that transforms raw data into meaningful insights by effectively integrating various analysis algorithms. In this paper, we propose a novel statistical test designed to assess the statistical significance of data analysis pipelines. Our approach allows for the systematic development of valid statistical tests applicable to any data analysis pipeline configuration composed of a set of data analysis components. We have developed this framework by adapting selective inference, which has gained recent attention as a new statistical inference technique for data-driven hypotheses. The proposed statistical test is theoretically designed to control the type I error at the desired significance level in finite samples. As examples, we consider a class of pipelines composed of three missing value imputation algorithms, three outlier detection algorithms, and three feature selection algorithms. We confirm the validity of our statistical test through experiments with both synthetic and real data for this class of data analysis pipelines. Additionally, we present an implementation framework that facilitates testing across any configuration of data analysis pipelines in this class without extra implementation costs.

Distributionally Robust Safe Sample Screening

In this study, we propose a machine learning method called Distributionally Robust Safe Sample Screening (DRSSS). DRSSS aims to identify unnecessary training samples, even when the distribution of the training samples changes in the future. To achieve this, we effectively combine the distributionally robust (DR) paradigm, which aims to enhance model robustness against variations in data distribution, with the safe sample screening (SSS), which identifies unnecessary training samples prior to model training. Since we need to consider an infinite number of scenarios regarding changes in the distribution, we applied SSS because it does not require model training after the change of the distribution. In this paper, we employed the covariate shift framework to represent the distribution of training samples and reformulated the DR covariate-shift problem as a weighted empirical risk minimization problem, where the weights are subject to uncertainty within a predetermined range. By extending the existing SSS technique to accommodate this weight uncertainty, the DRSSS method is capable of reliably identifying unnecessary samples under any future distribution within a specified range. We provide a theoretical guarantee for the DRSSS method and validate its performance through numerical experiments on both synthetic and real-world datasets.

Crystal-LSBO: Automated Design of De Novo Crystals with Latent Space Bayesian Optimization

Generative modeling of crystal structures is significantly challenged by the complexity of input data, which constrains the ability of these models to explore and discover novel crystals. This complexity often confines de novo design methodologies to merely small perturbations of known crystals and hampers the effective application of advanced optimization techniques. One such optimization technique, Latent Space Bayesian Optimization (LSBO) has demonstrated promising results in uncovering novel objects across various domains, especially when combined with Variational Autoencoders (VAEs). Recognizing LSBO's potential and the critical need for innovative crystal discovery, we introduce Crystal-LSBO, a de novo design framework for crystals specifically tailored to enhance explorability within LSBO frameworks. Crystal-LSBO employs multiple VAEs, each dedicated to a distinct aspect of crystal structure: lattice, coordinates, and chemical elements, orchestrated by an integrative model that synthesizes these components into a cohesive output. This setup not only streamlines the learning process but also produces explorable latent spaces thanks to the decreased complexity of the learning task for each model, enabling LSBO approaches to operate. Our study pioneers the use of LSBO for de novo crystal design, demonstrating its efficacy through optimization tasks focused mainly on formation energy values. Our results highlight the effectiveness of our methodology, offering a new perspective for de novo crystal discovery.

Distributionally Robust Safe Screening

In this study, we propose a method Distributionally Robust Safe Screening (DRSS), for identifying unnecessary samples and features within a DR covariate shift setting. This method effectively combines DR learning, a paradigm aimed at enhancing model robustness against variations in data distribution, with safe screening (SS), a sparse optimization technique designed to identify irrelevant samples and features prior to model training. The core concept of the DRSS method involves reformulating the DR covariate-shift problem as a weighted empirical risk minimization problem, where the weights are subject to uncertainty within a predetermined range. By extending the SS technique to accommodate this weight uncertainty, the DRSS method is capable of reliably identifying unnecessary samples and features under any future distribution within a specified range. We provide a theoretical guarantee of the DRSS method and validate its performance through numerical experiments on both synthetic and real-world datasets.

Statistical Test for Generated Hypotheses by Diffusion Models

The enhanced performance of AI has accelerated its integration into scientific research. In particular, the use of generative AI to create scientific hypotheses is promising and is increasingly being applied across various fields. However, when employing AI-generated hypotheses for critical decisions, such as medical diagnoses, verifying their reliability is crucial. In this study, we consider a medical diagnostic task using generated images by diffusion models, and propose a statistical test to quantify its reliability. The basic idea behind the proposed statistical test is to employ a selective inference framework, where we consider a statistical test conditional on the fact that the generated images are produced by a trained diffusion model. Using the proposed method, the statistical reliability of medical image diagnostic results can be quantified in the form of a p-value, allowing for decision-making with a controlled error rate. We show the theoretical validity of the proposed statistical test and its effectiveness through numerical experiments on synthetic and brain image datasets.

Statistical Test for Anomaly Detections by Variational Auto-Encoders

In this study, we consider the reliability assessment of anomaly detection (AD) using Variational Autoencoder (VAE). Over the last decade, VAE-based AD has been actively studied in various perspective, from method development to applied research. However, when the results of ADs are used in high-stakes decision-making, such as in medical diagnosis, it is necessary to ensure the reliability of the detected anomalies. In this study, we propose the VAE-AD Test as a method for quantifying the statistical reliability of VAE-based AD within the framework of statistical testing. Using the VAE-AD Test, the reliability of the anomaly regions detected by a VAE can be quantified in the form of p-values. This means that if an anomaly is declared when the p-value is below a certain threshold, it is possible to control the probability of false detection to a desired level. Since the VAE-AD Test is constructed based on a new statistical inference framework called selective inference, its validity is theoretically guaranteed in finite samples. To demonstrate the validity and effectiveness of the proposed VAE-AD Test, numerical experiments on artificial data and applications to brain image analysis are conducted.

Multimodal Co-orchestration for Exploring Structure-Property Relationships in Combinatorial Libraries via Multi-Task Bayesian Optimization

The rapid growth of automated and autonomous instrumentations brings forth an opportunity for the co-orchestration of multimodal tools, equipped with multiple sequential detection methods, or several characterization tools to explore identical samples. This can be exemplified by the combinatorial libraries that can be explored in multiple locations by multiple tools simultaneously, or downstream characterization in automated synthesis systems. In the co-orchestration approaches, information gained in one modality should accelerate the discovery of other modalities. Correspondingly, the orchestrating agent should select the measurement modality based on the anticipated knowledge gain and measurement cost. Here, we propose and implement a co-orchestration approach for conducting measurements with complex observables such as spectra or images. The method relies on combining dimensionality reduction by variational autoencoders with representation learning for control over the latent space structure, and integrated into iterative workflow via multi-task Gaussian Processes (GP). This approach further allows for the native incorporation of the system's physics via a probabilistic model as a mean function of the GP. We illustrated this method for different modalities of piezoresponse force microscopy and micro-Raman on combinatorial $Sm-BiFeO_3$ library. However, the proposed framework is general and can be extended to multiple measurement modalities and arbitrary dimensionality of measured signals. The analysis code that supports the funding is publicly available at https://github.com/Slautin/2024_Co-orchestration.

Statistical Test for Attention Map in Vision Transformer

The Vision Transformer (ViT) demonstrates exceptional performance in various computer vision tasks. Attention is crucial for ViT to capture complex wide-ranging relationships among image patches, allowing the model to weigh the importance of image patches and aiding our understanding of the decision-making process. However, when utilizing the attention of ViT as evidence in high-stakes decision-making tasks such as medical diagnostics, a challenge arises due to the potential of attention mechanisms erroneously focusing on irrelevant regions. In this study, we propose a statistical test for ViT's attentions, enabling us to use the attentions as reliable quantitative evidence indicators for ViT's decision-making with a rigorously controlled error rate. Using the framework called selective inference, we quantify the statistical significance of attentions in the form of p-values, which enables the theoretically grounded quantification of the false positive detection probability of attentions. We demonstrate the validity and the effectiveness of the proposed method through numerical experiments and applications to brain image diagnoses.

Selective Inference for Changepoint detection by Recurrent Neural Network

In this study, we investigate the quantification of the statistical reliability of detected change points (CPs) in time series using a Recurrent Neural Network (RNN). Thanks to its flexibility, RNN holds the potential to effectively identify CPs in time series characterized by complex dynamics. However, there is an increased risk of erroneously detecting random noise fluctuations as CPs. The primary goal of this study is to rigorously control the risk of false detections by providing theoretically valid p-values to the CPs detected by RNN. To achieve this, we introduce a novel method based on the framework of Selective Inference (SI). SI enables valid inferences by conditioning on the event of hypothesis selection, thus mitigating selection bias. In this study, we apply SI framework to RNN-based CP detection, where characterizing the complex process of RNN selecting CPs is our main technical challenge. We demonstrate the validity and effectiveness of the proposed method through artificial and real data experiments.