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COULD DROPPING A FEW CELLS CHANGE THE TAKEAWAYS FROM DIFFERENTIAL EXPRESSION?

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arXiv 2023年

作者： Shiffman, Miriam Giordano, Ryan Broderick, Tamara MIT Computational & Systems Biology Program United States MIT Dept. of Electrical Engineering & Computer Science United States UC Berkeley Dept. of Statistics United States

Analysis of differential gene expression plays a fundamental role in biology toward illuminating the molecular mechanisms driving a difference between groups (e.g., due to treatment or disease). While any analysis is run on particular cells or samples, the intent is to generalize to future occurrences of the treatment or disease. Implicitly, generalization is justified under the assumption that present and future samples are independent and identically distributed from the same population. Though this assumption is always false, we might hope that any deviation from the assumption is small enough that A) fundamental conclusions of the analysis still hold, and B) standard tools like standard error, significance, and power still reflect generalizability. Conversely, we might worry about these deviations, and reliance on standard statistical tools, if conclusions could be substantively changed by dropping a very small fraction of observations. While checking every small fraction is computationally intractable, recent work develops an approximation to identify when such an influential subset exists. Building on this work, we develop a metric for dropping-data robustness of differential expression;namely, we cast the analysis in a differentiable form suitable to the approximation, extend the approximation to models whose hyperparameters depend on the full dataset, and extend the notion of a data point from a single cell to a pseudobulk observation. We then overcome the inherent non-differentiability of gene set enrichment analysis to develop an additional approximation for the robustness of top gene sets. We use our tool to assess the robustness of differential expression for published single-cell RNA-seq data, and discover that thousands of genes can have their results flipped by dropping Copyright © 2023, The Authors. All rights reserved.

关键词： Diseases

Ordinal Classification Method for the Evaluation Of Thai Non-life Insurance Companies

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International Journal of Computer Science Issues 2012年第1 1-2期9卷 362-366页

作者： Jhonpita, Phaiboon Sinthupinyo, Sukree Chaiyawat, Thitivadee Technopreneurship and Innovation Management Program Graduate School Chulalongkorn University Bangkok Thailand Department of Computer Engineering Faculty of Engineering Chulalongkorn University Bangkok Thailand Department of Statistics Faculty of Commerce and Accountancy Chulalongkorn University Bangkok Thailand

This paper proposes a use of an ordinal classifier to evaluate the financial solidity of non-life insurance companies as strong, moderate, weak, and insolvency. This study constructed an efficient classification model that can be used by regulators to evaluate the financial solidity and to determine the priority of further examination as an early warning system. The proposed model is beneficial to policy-makers to create guidelines for the solvency regulations and roles of the government in protecting the public against insolvency. © 2012 International Journal of Computer Science Issues.

关键词： Insurance

Classification of EEG-based brain connectivity networks in schizophrenia using a multi-domain connectome convolutional neural network

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arXiv 2019年

作者： Phang, Chun-Ren Ting, Chee-Ming Noman, Fuad Ombao, Hernando School of Biomedical Engineering & Health Sciences Universiti Teknologi Malaysia Skudai Johor81310 Malaysia Statistics Program King Abdullah University of Science and Technology Thuwal23955 Saudi Arabia

Objective: We exploit altered patterns in brain functional connectivity as features for automatic discriminative analysis of neuropsychiatric patients. Deep learning methods have been introduced to functional network classification only very recently for fMRI, and the proposed architectures essentially focused on a single type of connectivity measure. Methods: We propose a deep convolutional neural network (CNN) framework for classification of electroencephalogram (EEG)-derived brain connectome in schizophrenia (SZ). To capture complementary aspects of disrupted connectivity in SZ, we explore combination of various connectivity features consisting of time and frequency-domain metrics of effective connectivity based on vector autoregressive model and partial directed coherence, and complex network measures of network topology. We design a novel multi-domain connectome CNN (MDC-CNN) based on a parallel ensemble of 1D and 2D CNNs to integrate the features from various domains and dimensions using different fusion strategies. Results: Hierarchical latent representations learned by the multiple convolutional layers from EEG connectivity reveal apparent group differences between SZ and healthy controls (HC). Results on a large resting-state EEG dataset show that the proposed CNNs significantly outperform traditional support vector machine classifiers. The MDC-CNN with combined connectivity features further improves performance over single-domain CNNs using individual features, achieving remarkable accuracy of 93.06% with a decision-level fusion. Conclusion: The proposed MDC-CNN by integrating information from diverse brain connectivity descriptors is able to accurately discriminate SZ from HC. Significance: The new framework is potentially useful for developing diagnostic tools for SZ and other disorders. Copyright © 2019, The Authors. All rights reserved.

关键词： Electroencephalography

Bayesian Parameter Inference for Partially Observed SDEs driven by Fractional Brownian Motion

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arXiv 2022年

作者： Maama, Mohamed Jasra, Ajay Ombao, Hernando Applied Mathematics and Computational Science Program Computer Electrical and Mathematical Sciences and Engineering Division King Abdullah University of Science and Technology Thuwal23955 Saudi Arabia Statistics Program Computer Electrical and Mathematical Sciences and Engineering Division King Abdullah University of Science and Technology Thuwal23955 Saudi Arabia

In this paper we consider Bayesian parameter inference for partially observed fractional Brownian motion (fBM) models. The approach we follow is to time-discretize the hidden process and then to design Markov chain Monte Carlo (MCMC) algorithms to sample from the posterior density on the parameters given data. We rely on a novel representation of the time discretization, which seeks to sample from an approximation of the posterior and then corrects via importance sampling;the approximation reduces the time (in terms of total observation time T) by O(T). This method is extended by using a multilevel MCMC method which can reduce the computational cost to achieve a given mean square error (MSE) versus using a single time discretization. Our methods are illustrated on simulated and real data. Copyright © 2022, The Authors. All rights reserved.

关键词： Mean square error

Artificial intelligence for modelling infectious disease epidemics

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Nature 2025年第8051期638卷 623-635页

作者： Kraemer, Moritz U. G. Tsui, Joseph L.-H. Chang, Serina Y. Lytras, Spyros Khurana, Mark P. Vanderslott, Samantha Bajaj, Sumali Scheidwasser, Neil Curran-Sebastian, Jacob Liam Semenova, Elizaveta Zhang, Mengyan Unwin, H. Juliette T. Watson, Oliver J. Mills, Cathal Dasgupta, Abhishek Ferretti, Luca Scarpino, Samuel V. Koua, Etien Morgan, Oliver Tegally, Houriiyah Paquet, Ulrich Moutsianas, Loukas Fraser, Christophe Ferguson, Neil M. Topol, Eric J. Duchêne, David A. Stadler, Tanja Kingori, Patricia Parker, Michael J. Dominici, Francesca Shadbolt, Nigel Suchard, Marc A. Ratmann, Oliver Flaxman, Seth Holmes, Edward C. Gomez-Rodriguez, Manuel Schölkopf, Bernhard Donnelly, Christl A. Pybus, Oliver G. Cauchemez, Simon Bhatt, Samir Pandemic Sciences Institute University of Oxford Oxford United Kingdom Department of Biology University of Oxford Oxford United Kingdom Department of Electrical Engineering and Computer Science University of California Berkeley Berkeley CA United States UCSF UC Berkeley Joint Program in Computational Precision Health Berkeley CA United States Division of Systems Virology Department of Microbiology and Immunology The Institute of Medical Science The University of Tokyo Tokyo Japan Section of Epidemiology Department of Public Health University of Copenhagen Copenhagen Denmark Oxford Vaccine Group University of Oxford and NIHR Oxford Biomedical Research Centre Oxford United Kingdom Department of Epidemiology and Biostatistics Imperial College London London United Kingdom Department of Computer Science University of Oxford Oxford United Kingdom School of Mathematics University of Bristol Bristol United Kingdom MRC Centre for Global Infectious Disease Analysis School of Public Health Imperial College London London United Kingdom Department of Statistics University of Oxford Oxford United Kingdom Doctoral Training Centre University of Oxford Oxford United Kingdom Institute for Experiential AI Northeastern University MA Boston Thailand Santa Fe Institute Santa Fe NM United States World Health Organization Regional Office for Africa Brazzaville Congo WHO Hub for Pandemic and Epidemic Intelligence Health Emergencies Programme World Health Organization Berlin Germany Centre for Epidemic Response and Innovation (CERI) School for Data Science and Computational Thinking Stellenbosch University Stellenbosch South Africa African Institute for Mathematical Sciences (AIMS) South Africa Muizenberg Cape Town South Africa Genomics England London United Kingdom Scripps Research La Jolla CA United States Department of Biosystems Science and Engineering ETH Zürich Basel Switzerland Swiss Institute of Bioinformatics Lausanne Switzerland The Ethox Centre Nuffield

Infectious disease threats to individual and public health are numerous, varied and frequently unexpected. Artificial intelligence (AI) and related technologies, which are already supporting human decision making in economics, medicine and social science, have the potential to transform the scope and power of infectious disease epidemiology. Here we consider the application to infectious disease modelling of AI systems that combine machine learning, computational statistics, information retrieval and data science. We first outline how recent advances in AI can accelerate breakthroughs in answering key epidemiological questions and we discuss specific AI methods that can be applied to routinely collected infectious disease surveillance data. Second, we elaborate on the social context of AI for infectious disease epidemiology, including issues such as explainability, safety, accountability and ethics. Finally, we summarize some limitations of AI applications in this field and provide recommendations for how infectious disease epidemiology can harness most effectively current and future developments in AI. © Springer Nature Limited 2025.

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Using spatial characteristics to aid automation of SOM segmentation of functional image data

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Using spatial characteristics to aid automation of SOM segme...

International Workshop on Self-Organizing Maps and Learning Vector Quantization, Clustering and Data Visualization (WSOM)

作者： Patrick O'Driscoll Erzsébet Merényi Robert Grossman Applied Physics Program Rice University Houston Texas Departments of Statistics and Electrical and Computer Engineering Rice University Houston Texas Department of Neurosurgery Houston Methodist Neurological Institute Houston Texas

ISBN: (纸本)9781509066391

We propose a new similarity measure, Combined Connectivity and Spatial Adjacency (CCSA), to be used in hierarchical agglomerative clustering (HAC) for automated segmentation of Self-Organizing Maps (SOMs, Kohonen [1]). The CCSA measure is specifically designed to assist segmentation of large, complex, functional image data by exploiting general spatial characteristics of such data. The proposed CCSA measure is constructed from two strong indicators of cluster structure: the degree of localization of data points in physical space and the degree of connectivity of SOM prototypes (as defined by Taçdemir and Merényi [2]). The new measure is expected to enhance cluster capture in large functional image data cubes such as hyperspectral imagery or fMRI brain images, where many relevant clusters exist with widely varying statistical properties and in complex relationships both in feature space and in physical (image) space. We demonstrate the effectiveness of our approach using the CCSA measure on progressively complex synthetic spatial data and on real fMRI brain data.

关键词： Prototypes Resource description framework Extraterrestrial measurements Brain Spatial databases Image segmentation Hyperspectral imaging

Flor Revisited(Again):eQTL and Mutational Analysis of NB-LRR Mediated Immunity to Powdery Mildew in Barley

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Journal of Integrative Agriculture 2014年第2期13卷 237-243页

作者： Roger Wise Priyanka Surana Greg Fuerst Ruo Xu Divya Mistry Julie Dickerson Dan Nettleton Corn Insects and Crop Genetics Research Unit U.S.Department of Agriculture-Agricultural Research ServiceIowa State UniversityAmesIowa 50011USA Department of Plant Pathology & Microbiology Center for Plant Responses to Environmental StressesIowa State UniversityAmesIowa 50011USA Bioinformatics and Computational Biology Graduate Program Iowa State UniversityAmesIowa 50011USA Department of Statistics Iowa State UniversityAmesIowa 50011USA Department of Electrical and Computer Engineering Iowa State UniversityAmesIowa 50011USA

Genes encoding early signaling events in pathogen defense often are identified only by their phenotype. Such genes involved in barley-powdery mildew interactions include Mla, specifying race-specific resistance; Rarl （Required for Mla12-specified resistance1）, and Roml （Restoration of Mla-specified resistancel）. The HSP90-SGT1-RAR1 complex appears to function as chaperone in MLA-specified resistance, however, much remains to be discovered regarding the precise signaling underlying plant immunity. Genetic analyses of fast-neutron mutants derived from CI 16151 （Mla6） uncovered a novel locus, designated Rar3 （R_equired for Mla6-specified resitance3）. Rar3 segregates independent of Mla6 and Rarl, and rar3 mutants are susceptible to Blumeria graminis f. sp. hordei （Bgh） isolate 5874 （A VRar）, whereas, wild-type progenitor plants are resistant. Comparative expression analyses of the rar3 mutant vs. its wild-type progenitor were conducted via Barleyl GeneChip and GAIIx paired-end RNA-Seq. Whereas Rarl affects transcription of relatively few genes; Rar3 appears to influence thousands, notably in genes controlling ATP binding, catalytic activity, transcription, and phosphorylation; possibly membrane bound or in the nucleus, eQTL analysis of a segregating doubled haploid population identified over two-thousand genes as being regulated by Mla （q value/FDR=0.00001）, a subset of which are significant in Rar3 interactions. The intersection of datasets derived from mla-loss-of-function mutants, Mla-associated eQTL, and rar3-mediated transcriptome reprogramming are narrowing the focus on essential genes required for Mla-specified immunity.

关键词： eQTL transcript profiling immunity resistance signaling barley Blumeria graminis

A Dynamical Clipping Approach with Task Feedback for Proximal Policy Optimization

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arXiv 2023年

作者： Zhang, Ziqi Xu, Jingzehua Zhuang, Zifeng Zhang, Hongyin Liu, Jinxin Wang, Donglin Zhang, Shuai Lyu, Shangke School of Engineering WestLake University China MicroMasters Program in Statistics and Data Science Massachusetts Institute of Technology United States Department of Data Science New Jersey Institute of Technology United States

Proximal Policy Optimization (PPO) has been broadly applied to robotics learning, showcasing stable training performance. However, the fixed clipping bound setting may limit the performance of PPO. Specifically, there is no theoretical proof that the optimal clipping bound remains consistent throughout the entire training process. Meanwhile, previous researches suggest that a fixed clipping bound restricts the policy's ability to explore. Therefore, many past studies have aimed to dynamically adjust the PPO clipping bound to enhance PPO's performance. However, the objective of these approaches are not directly aligned with the objective of reinforcement learning (RL) tasks, which is to maximize the cumulative Return. Unlike previous clipping approaches, we propose a bi-level proximal policy optimization objective that can dynamically adjust the clipping bound to better reflect the preference (maximizing Return) of these RL tasks. Based on this bi-level proximal policy optimization paradigm, we introduce a new algorithm named Preference based Proximal Policy Optimization (Pb-PPO). Pb-PPO utilizes a multi-armed bandit approach to refelect RL preference, recommending the clipping bound for PPO that can maximizes the current Return. Therefore, Pb-PPO results in greater stability and improved performance compared to PPO with a fixed clipping bound. We test Pb-PPO on locomotion benchmarks across multiple environments, including Gym-Mujoco and legged-gym. Additionally, we validate Pb-PPO on customized navigation tasks. Meanwhile, we conducted comparisons with PPO using various fixed clipping bounds and various of clipping approaches. The experimental results indicate that Pb-PPO demonstrates superior training performance compared to PPO and its variants. Copyright © 2023, The Authors. All rights reserved.

关键词： Reinforcement learning

A Consensus Privacy Metrics Framework for Synthetic Data

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arXiv 2025年

作者： Pilgram, Lisa Dankar, Fida K. Drechsler, Jörg Elliot, Mark Domingo-Ferrer, Josep Francis, Paul Kantarcioglu, Murat Kong, Linglong Malin, Bradley Muralidhar, Krishnamurty Myles, Puja Prasser, Fabian Raisaro, Jean Louis Yan, Chao El Emam, Khaled School of Epidemiology and Public Health University of Ottawa ON Canada CHEO Research Institute ON Canada Department of Nephrology and Medical Intensive Care Charité – Universitätsmedizin Berlin Berlin Germany Department for Statistical Methods Institute for Employment Research Nuernberg Germany Institute for Statistics Ludwig-Maximilians-Universität Munich Germany Joint Program in Survey Methodology University of Maryland United States The Cathie Marsh Institute Research School of Social Sciences University of Manchester Manchester United Kingdom Department of Computer Engineering and Mathematics Universitat Rovira i Virgili Catalonia Tarragona Spain Max Planck Institute for Software Systems Germany Department of Computer Science Virginia Tech United States Department of Mathematical and Statistical Sciences University of Alberta Alberta Canada Department of Biomedical Informatics Vanderbilt University Medical Center NashvilleTN United States Department of Biostatistics Vanderbilt University Medical Center NashvilleTN United States Department of Computer Science Vanderbilt University NashvilleTN United States Department of Marketing and Supply Chain Management University of Oklahoma Oklahoma United States Medicines and Healthcare products Regulatory Agency London United Kingdom Berlin Institute of Health at Charité Universitätsmedizin Berlin Medical Informatics Group Berlin Germany Biomedical Data Science Center University Hospital Lausanne Lausanne Switzerland

Synthetic data generation is one approach for sharing individual-level data. However, to meet legislative requirements, it is necessary to demonstrate that the individuals’ privacy is adequately protected. There is no consolidated standard for measuring privacy in synthetic data. Through an expert panel and consensus process, we developed a framework for evaluating privacy in synthetic data. Our findings indicate that current similarity metrics fail to measure identity disclosure, and their use is discouraged. For differentially private synthetic data, a privacy budget other than close to zero was not considered interpretable. There was consensus on the importance of membership and attribute disclosure, both of which involve inferring personal information about an individual without necessarily revealing their identity. The resultant framework provides precise recommendations for metrics that address these types of disclosures effectively. Our findings further present specific opportunities for future research that can help with widespread adoption of synthetic data. © 2025, CC BY.

关键词： Differential privacy