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1. An Efficient Linear Mixed Model Framework for Meta-Analytic Association Studies Across Multiple Contexts

   Jew, Brandon; Li, Jiajin; Sankararaman, Sriram; Sul, Jae-Hoon (January 2021, 21st International Workshop on Algorithms in Bioinformatics, {WABI})

   Linear mixed models (LMMs) can be applied in the meta-analyses of responses from individuals across multiple contexts, increasing power to detect associations while accounting for confounding effects arising from within-individual variation. However, traditional approaches to fitting these models can be computationally intractable. Here, we describe an efficient and exact method for fitting a multiple-context linear mixed model. Whereas existing exact methods may be cubic in their time complexity with respect to the number of individuals, our approach for multiple-context LMMs (mcLMM) is linear. These improvements allow for large-scale analyses requiring computing time and memory magnitudes of order less than existing methods. As examples, we apply our approach to identify expression quantitative trait loci from large-scale gene expression data measured across multiple tissues as well as joint analyses of multiple phenotypes in genomewide association studies at biobank scale. 

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2. Scalable Algorithms for Learning High-Dimensional Linear Mixed Models

   Zilong Tan, Kimberly Roche (January 2018, Proceedings of the Thirty-Fourth Conference on Uncertainty in Artificial Intelligence)

   Linear mixed models (LMMs) are used extensively to model observations that are not independent. Parameter estimation for LMMs can be computationally prohibitive on big data. State-of-the-art learning algorithms require computational complexity which depends at least linearly on the dimension p of the covariates, and often use heuristics that do not offer theoretical guarantees. We present scalable algorithms for learning high-dimensional LMMs with sublinear computational complexity dependence on p. Key to our approach are novel dual estimators which use only kernel functions of the data, and fast computational techniques based on the subsampled randomized Hadamard transform. We provide theoretical guarantees for our learning algorithms, demonstrating the robustness of parameter estimation. Finally, we complement the theory with experiments on large synthetic and real data. 

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3. Exact quantitative probabilistic model checking through rational search

   https://doi.org/10.1007/s10703-020-00348-y  

   Mathur, Umang; Bauer, Matthew S.; Chadha, Rohit; Sistla, A. Prasad; Viswanathan, Mahesh (July 2020, Formal Methods in System Design)

   Model checking systems formalized using probabilistic models such as discrete time Markov chains (DTMCs) and Markov decision processes (MDPs) can be reduced to computing constrained reachability properties. Linear programming methods to compute reachability probabilities for DTMCs and MDPs do not scale to large models. Thus, model checking tools often employ iterative methods to approximate reachability probabilities. These approximations can be far from the actual probabilities, leading to inaccurate model checking results. On the other hand, specialized techniques employed in existing state-of-the-art exact quantitative model checkers, don’t scale as well as their iterative counterparts. In this work, we present a new model checking algorithm that improves the approximate results obtained by scalable iterative techniques to compute exact reachability probabilities. Our techniques are implemented as an extension of the PRISM model checker and are evaluated against other exact quantitative model checking engines. 

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4. BGWAS: Bayesian variable selection in linear mixed models with nonlocal priors for genome-wide association studies

   https://doi.org/10.1186/s12859-023-05316-x  

   Williams, Jacob; Xu, Shuangshuang; Ferreira, Marco A. (December 2023, BMC Bioinformatics)

   Abstract Background Genome-wide association studies (GWAS) seek to identify single nucleotide polymorphisms (SNPs) that cause observed phenotypes. However, with highly correlated SNPs, correlated observations, and the number of SNPs being two orders of magnitude larger than the number of observations, GWAS procedures often suffer from high false positive rates. Results We propose BGWAS, a novel Bayesian variable selection method based on nonlocal priors for linear mixed models specifically tailored for genome-wide association studies. Our proposed method BGWAS uses a novel nonlocal prior for linear mixed models (LMMs). BGWAS has two steps: screening and model selection. The screening step scans through all the SNPs fitting one LMM for each SNP and then uses Bayesian false discovery control to select a set of candidate SNPs. After that, a model selection step searches through the space of LMMs that may have any number of SNPs from the candidate set. A simulation study shows that, when compared to popular GWAS procedures, BGWAS greatly reduces false positives while maintaining the same ability to detect true positive SNPs. We show the utility and flexibility of BGWAS with two case studies: a case study on salt stress in plants, and a case study on alcohol use disorder. Conclusions BGWAS maintains and in some cases increases the recall of true SNPs while drastically lowering the number of false positives compared to popular SMA procedures. 

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5. On the Robustness of Large Multimodal Models Against Image Adversarial Attacks

   Cui, Xuanming; Aparcedo, Alejandro; Jang, Young Kyun; Lim, Ser-Nam (June 2024, Proceedings of the IEEE/CVF Conference on Computer Vision and Pattern Recognition (CVPR))

   Recent advances in instruction tuning have led to the development of State-of-the-Art Large Multimodal Models (LMMs). Given the novelty of these models the impact of visual adversarial attacks on LMMs has not been thoroughly examined. We conduct a comprehensive study of the robustness of various LMMs against different adversarial attacks evaluated across tasks including image classification image captioning and Visual Question Answer (VQA). We find that in general LMMs are not robust to visual adversarial inputs. However our findings suggest that context provided to the model via prompts--such as questions in a QA pair--helps to mitigate the effects of visual adversarial inputs. Notably the LMMs evaluated demonstrated remarkable resilience to such attacks on the ScienceQA task with only an 8.10% drop in performance compared to their visual counterparts which dropped 99.73%. We also propose a new approach to real-world image classification which we term query decomposition. By incorporating existence queries into our input prompt we observe diminished attack effectiveness and improvements in image classification accuracy. This research highlights a previously under explored facet of LMM robustness and sets the stage for future work aimed at strengthening the resilience of multimodal systems in adversarial environments. 

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