For most diseases, building large databases of labeled genetic data is an expensive and time-demanding task. To address this, we introduce genetic Generative Adversarial Networks (gGAN), a semi-supervised approach based on an innovative GAN architecture to create large synthetic genetic data sets starting with a small amount of labeled data and a large amount of unlabeled data. Our goal is to determine the propensity of a new individual to develop the severe form of the illness from their genetic profile alone. The proposed model achieved satisfactory results using real genetic data from different datasets and populations, in which the test populations may not have the same genetic profiles. The proposed model is self-aware and capable of determining whether a new genetic profile has enough compatibility with the data on which the network was trained and is thus suitable for prediction. The code and datasets used can be found at https://github.com/caio-davi/gGAN.
Given genetic variations and various phenotypical traits, such as Magnetic Resonance Imaging (MRI) features, we consider two important and related tasks in biomedical research: i)to select genetic and phenotypical markers for disease diagnosis and ii) to identify associations between genetic and phenotypical data. These two tasks are tightly coupled because underlying associations between genetic variations and phenotypical features contain the biological basis for a disease. While a variety of sparse models have been applied for disease diagnosis and canonical correlation analysis and its ext…
IQVIA（艾昆纬）；University of California, Los Angeles（加利福尼亚大学洛杉矶分校）
Rare diseases affect a relatively small number of people, which limits investment in research for treatments and cures. Developing an efficient method for rare disease detection is a crucial first step towards subsequent clinical research. In this paper, we present a semi-supervised learning framework for rare disease detection using generative adversarial networks. Our method takes advantage of the large amount of unlabeled data for disease detection and achieves the best results in terms of precision-recall score compared to baseline techniques.
IQVIA Inc.（IQVIA公司）；Georgia Institute of Technology（佐治亚理工学院）
Rare diseases affecting 350 million individuals are commonly associated with delay in diagnosis or misdiagnosis. To improve those patients' outcome, rare disease detection is an important task for identifying patients with rare conditions based on longitudinal medical claims. In this paper, we present a deep learning method for detecting patients with exocrine pancreatic insufficiency (EPI) (a rare disease). The contribution includes 1) a large longitudinal study using 7 years medical claims from 1.8 million patients including 29,149 EPI patients, 2) a new deep learning model using generative …
Lehigh University（利哈伊大学）；University of Illinois at Chicago（伊利诺伊大学芝加哥分校）；NYU Grossman School of Medicine（纽约大学格罗斯曼医学院）
Normative modeling is an emerging and promising approach to effectively study disorder heterogeneity in individual participants. In this study, we propose a novel normative modeling method by combining conditional variational autoencoder with adversarial learning (ACVAE) to identify brain dysfunction in Alzheimer's Disease (AD). Specifically, we first train a conditional VAE on the healthy control (HC) group to create a normative model conditioned on covariates like age, gender and intracranial volume. Then we incorporate an adversarial training process to construct a discriminative feature sp…
IQVIA（艾昆纬）；The Pennsylvania State University（宾夕法尼亚州立大学）；Georgia Institute of Technology（佐治亚理工学院）
Rare diseases affect hundreds of millions of people worldwide but are hard to detect since they have extremely low prevalence rates (varying from 1/1,000 to 1/200,000 patients) and are massively underdiagnosed. How do we reliably detect rare diseases with such low prevalence rates? How to further leverage patients with possibly uncertain diagnosis to improve detection? In this paper, we propose a Complementary pattern Augmentation (CONAN) framework for rare disease detection. CONAN combines ideas from both adversarial training and max-margin classification. It first learns self-attentive and h…
Melanoma is the most lethal type of skin cancer. Patients are vulnerable to mental health illnesses which can reduce the effectiveness of the cancer treatment and the patients adherence to drug plans. It is crucial to preserve the mental health of patients while they are receiving treatment. However, current art therapy approaches are not personal and unique to the patient. We aim to provide a well-trained image style transfer model that can quickly generate unique art from personal dermoscopic melanoma images as an additional tool for art therapy in disease management of melanoma. Visual art …
Hasso Plattner Institute（哈索·普拉特纳研究所）；Universität Potsdam（波茨坦大学）；Max Delbrück Center for Molecular Medicine（马克斯·德尔布吕克分子医学中心）
For precision medicine and personalized treatment, we need to identify predictive markers of disease. We focus on Alzheimer's disease (AD), where magnetic resonance imaging scans provide information about the disease status. By combining imaging with genome sequencing, we aim at identifying rare genetic markers associated with quantitative traits predicted from convolutional neural networks (CNNs), which traditionally have been derived manually by experts. Kernel-based tests are a powerful tool for associating sets of genetic variants, but how to optimally model rare genetic variants is still …
1 School of Computing, Informatics；3 Imaging Genetics Center, Institute for Neuroimaging
Genome-wide association studies (GWAS) offer new opportunities to identify genetic risk factors for Alzheimer's disease (AD). Recently, collaborative efforts across different institutions emerged that enhance the power of many existing techniques on individual institution data. However, a major barrier to collaborative studies of GWAS is that many institutions need to preserve individual data privacy. To address this challenge, we propose a novel distributed framework, termed Local Query Model (LQM) to detect risk SNPs for AD across multiple research institutions. To accelerate the learning pr…
1 School of Computing, Informatics；2 Imaging Genetics Center, Institute for Neuroimaging
Genome-wide association studies (GWAS) have achieved great success in the genetic study of Alzheimer's disease (AD). Collaborative imaging genetics studies across different research institutions show the effectiveness of detecting genetic risk factors. However, the high dimensionality of GWAS data poses significant challenges in detecting risk SNPs for AD. Selecting relevant features is crucial in predicting the response variable. In this study, we propose a novel Distributed Feature Selection Framework (DFSF) to conduct the large-scale imaging genetics studies across multiple institutions. To…
Multi-megabase scale genome interpretation with genetic language models
GSK plc（葛兰素史克公司）；Max Planck Institute for Intelligent Systems（马克斯·普朗克智能系统研究所）；ELLIS Institute（欧洲学习与智能系统研究所）；Harvard Medical School（哈佛医学院）；ETH Zurich（苏黎世联邦理工学院）；Nuffield Department of Population Health, University of Oxford（牛津大学纳菲尔德人口健康系）
City University（城市大学）；East West University（东西大学）；Bangladesh University of Engineering and Technology（孟加拉工程技术大学）
Worldwide research shows that millions of lives lost per year because of heart disease. The healthcare sector produces massive volumes of data on heart disease that are sadly not used to locate secret knowledge for successful decision making. One of the most important aspects at this moment is detecting heart disease at an early stage. Researchers have applied distinct techniques to the UCI Machine Learning heart disease dataset. Many researchers have tried to apply some complex techniques to this dataset, where detailed studies are still missing. In this paper, Principal Component Analysis (P…
University of Pennsylvania（宾夕法尼亚大学）；University of Southern California（南加州大学）；Lausanne University Hospital (CHUV) and University of Lausanne（洛桑大学医院（CHUV）和洛桑大学）；University of Texas San Antonio Health Science Center（德克萨斯大学圣安东尼奥健康科学中心）；The University of Melbourne（墨尔本大学）；CSIRO（澳大利亚联邦科学与工业研究组织）；National Institute on Aging, National Institutes of Health（美国国立卫生研究院国家老龄化研究所）；Johns Hopkins University（约翰霍普金斯大学）；University of Wisconsin（威斯康星大学）；Washington University in St. Louis（圣路易斯华盛顿大学）；National Institute on Aging（国家老龄化研究所）
Disease heterogeneity has been a critical challenge for precision diagnosis and treatment, especially in neurologic and neuropsychiatric diseases. Many diseases can display multiple distinct brain phenotypes across individuals, potentially reflecting disease subtypes that can be captured using MRI and machine learning methods. However, biological interpretability and treatment relevance are limited if the derived subtypes are not associated with genetic drivers or susceptibility factors. Herein, we describe Gene-SGAN - a multi-view, weakly-supervised deep clustering method - which dissects dis…
We put forward a novel learning methodology for ensembles of decision trees based on a genetic algorithm which is able to train a decision tree for maximizing both its accuracy and its robustness to adversarial perturbations. This learning algorithm internally leverages a complete formal verification technique for robustness properties of decision trees based on abstract interpretation, a well known static program analysis technique. We implemented this genetic adversarial training algorithm in a tool called Meta-Silvae (MS) and we experimentally evaluated it on some reference datasets used in…
Background and purpose: Heart disease has been one of the most important causes of death in the last 10 years, so the use of classification methods to diagnose and predict heart disease is very important. If this disease is predicted before menstruation, it is possible to prevent high mortality of the disease and provide more accurate and efficient treatment methods. Materials and Methods: Due to the selection of input features, the use of basic algorithms can be very time-consuming. Reducing dimensions or choosing a good subset of features, without risking accuracy, has great importance for b…
2 Diabetes is a leading worldwide public health concern, and its increasing prevalence has significant health and economic importance in all nations. The condition is a multifactorial disorder with a complex aetiology. The genetic determinants remain largely elusive, with only a handful of identified candidate genes. Genome wide association studies (GWAS) promised to significantly enhance our understanding of genetic based determinants of common complex diseases. To date, 83 single nucleotide polymorphisms (SNPs) for type 2 diabetes have been identified using GWAS. Standard statistical tests f…
Cyber security adversaries and engagements are ubiquitous and ceaseless. We delineate Adversarial Genetic Programming for Cyber Security, a research topic that, by means of genetic programming (GP), replicates and studies the behavior of cyber adversaries and the dynamics of their engagements. Adversarial Genetic Programming for Cyber Security encompasses extant and immediate research efforts in a vital problem domain, arguably occupying a position at the frontier where GP matters. Additionally, it prompts research questions around evolving complex behavior by expressing different abstractions…
Diagnosing an inherited disease often requires identifying the pattern of inheritance in a patient's family. We represent family trees with genetic patterns of inheritance using hypergraphs and latent state space models to provide explainable inheritance pattern predictions. Our approach allows for exact causal inference over a patient's possible genotypes given their relatives' phenotypes. By design, inference can be examined at a low level to provide explainable predictions. Furthermore, we make use of human intuition by providing a method to assign hypothetical evidence to any inherited gen…
Unravelling Causal Genetic Biomarkers of Alzheimer's Disease via Neuron to Gene-token Backtracking in Neural Architecture: A Groundbreaking Reverse-Gene-Finder Approach
Global Blood Therapeutics（Global Blood Therapeutics（全球血液治疗公司））
The approval success rate of drug candidates is very low with the majority of failure due to safety and efficacy. Increasingly available high dimensional information on targets, drug molecules and indications provides an opportunity for ML methods to integrate multiple data modalities and better predict clinically promising drug targets. Notably, drug targets with human genetics evidence are shown to have better odds to succeed. However, a recent tensor factorization-based approach found that additional information on targets and indications might not necessarily improve the predictive accurac…
The choice of crossover and mutation strategies plays a crucial role in the searchability, convergence efficiency and precision of genetic algorithms. In this paper, a novel improved genetic algorithm is proposed by improving the crossover and mutation operation of the simple genetic algorithm, and it is verified by 15 test functions. The qualitative results show that, compared with three other mainstream swarm intelligence optimization algorithms, the algorithm can not only improve the global search ability, convergence efficiency and precision, but also increase the success rate of convergen…
Machine learning has been gaining traction in recent years to meet the demand for tools that can efficiently analyze and make sense of the ever-growing databases of biomedical data in health care systems around the world. However, effectively using machine learning methods requires considerable domain expertise, which can be a barrier of entry for bioinformaticians new to computational data science methods. Therefore, off-the-shelf tools that make machine learning more accessible can prove invaluable for bioinformaticians. To this end, we have developed an open source pipeline optimization too…
Most deep learning models are easily vulnerable to adversarial attacks. Various adversarial attacks are designed to evaluate the robustness of models and develop defense model. Currently, adversarial attacks are brought up to attack their own target model with their own evaluation metrics. And most of the black-box adversarial attack algorithms cannot achieve the expected success rate compared with white-box attacks. In this paper, comprehensive evaluation metrics are brought up for different adversarial attack methods. A novel perturbation optimized black-box adversarial attack based on genet…
A Generalized Genetic Random Field Method for the Genetic Association Analysis of Sequencing Data
University of Arkansas for Medical Sciences（阿肯色大学医学科学中心）；University of Michigan（密歇根大学）；Michigan State University（密歇根州立大学）；Case Western Reserve University（凯斯西储大学）
Feature Selection (FS) has become the focus of much research on decision support systems areas for which data sets with tremendous number of variables are analyzed. In this paper we present a new method for the diagnosis of Coronary Artery Diseases (CAD) founded on Genetic Algorithm (GA) wrapped Bayes Naive (BN) based FS. Basically, CAD dataset contains two classes defined with 13 features. In GA BN algorithm, GA generates in each iteration a subset of attributes that will be evaluated using the BN in the second step of the selection procedure. The final set of attribute contains the most rele…
IGAff: Benchmarking Adversarial Iterative and Genetic Affine Algorithms on Deep Neural Networks
Faculty of Automatic Control；Computers, National University of Science；National Institute for Research \& Development in Informatics - ICI Bucharest, Bucharest, Romania
Simon Fraser University（西蒙弗雷泽大学）；Wake Forest University（维克森林大学）；University of British Columbia（不列颠哥伦比亚大学）；Ohio State University Wexner Medical Center（俄亥俄州立大学韦克斯纳医学中心）；University of Miami Miller School of Medicine（迈阿密大学米勒医学院）；University of Nottingham（诺丁汉大学）
Background: The increasing availability of databases containing both magnetic resonance imaging (MRI) and genetic data allows researchers to utilize multimodal data to better understand the characteristics of dementia of Alzheimer's type (DAT). Objective: The goal of this study was to develop and analyze novel biomarkers that can help predict the development and progression of DAT. Methods: We used feature selection and ensemble learning classifier to develop an image/genotype-based DAT score that represents a subject's likelihood of developing DAT in the future. Three feature types were used:…
GestaltMML: Enhancing Rare Genetic Disease Diagnosis through Multimodal Machine Learning Combining Facial Images and Clinical Text
Raymond G. Perelman Center for Cellular and Molecular Therapeutics, Children’s Hospital of Philadelphia（雷蒙德·G·佩尔曼细胞与分子治疗中心，费城儿童医院）；Department of Mathematics, University of Pennsylvania（数学系，宾夕法尼亚大学）；Department of Biomedical Informatics, Columbia University Irving Medical Center（生物医学信息学系，哥伦比亚大学伊万斯医疗中心）；Department of Human Genetics, New York State Institute for Basic Research in Developmental Disabilities, Staten Island, NY, USA（人类遗传学系，纽约州发育障碍基础研究机构，纽约州史泰登岛）；Division of Human Genetics, Children’s Hospital of Philadelphia（人类遗传学部，费城儿童医院）；Department of Pediatrics, Boston Children’s Hospital, Harvard Medical School（儿科系，波士顿儿童医院，哈佛医学院）；Biology PhD Program, The Graduate Center, The City University of New York（生物学博士项目，纽约市立大学研究生中心）；Department of Genetics, Perelman School of Medicine, University of Pennsylvania（遗传学系，宾夕法尼亚大学佩尔曼医学学院）；Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania（儿科系，宾夕法尼亚大学佩尔曼医学学院）；Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania（病理学与实验室医学系，宾夕法尼亚大学佩尔曼医学学院）
Seoul National University（首尔国立大学）；Samsung Electronics Co. Ltd.（三星电子有限公司）；Seoul National University College of Medicine（首尔国立大学医学院）
Electronic health records (EHRs) have contributed to the computerization of patient records and can thus be used not only for efficient and systematic medical services, but also for research on biomedical data science. However, there are many missing values in EHRs when provided in matrix form, which is an important issue in many biomedical EHR applications. In this paper, we propose a two-stage framework that includes missing data imputation and disease prediction to address the missing data problem in EHRs. We compared the disease prediction performance of generative adversarial networks (GA…
University of Queensland（昆士兰大学）；Federal University Kashere（卡谢雷联邦大学）
Widely used deep learning models are found to have poor robustness. Little noises can fool state-of-the-art models into making incorrect predictions. While there is a great deal of high-performance attack generation methods, most of them directly add perturbations to original data and measure them using L_p norms; this can break the major structure of data, thus, creating invalid attacks. In this paper, we propose a black-box attack, which, instead of modifying original data, modifies latent features of data extracted by an autoencoder; then, we measure noises in semantic space to protect the …
Diabetes is currently one of the most common, dangerous, and costly diseases in the world that is caused by an increase in blood sugar or a decrease in insulin in the body. Diabetes can have detrimental effects on people's health if diagnosed late. Today, diabetes has become one of the challenges for health and government officials. Prevention is a priority, and taking care of people's health without compromising their comfort is an essential need. In this study, the Ensemble training methodology based on genetic algorithms are used to accurately diagnose and predict the outcomes of diabetes m…
South China University of Technology（华南理工大学）；Inception Institute of Artificial Intelligence（Inception人工智能研究所）；Chinese Academy of Sciences（中国科学院）
Recently, deep neural networks (DNNs) have made great progress on automated diagnosis with chest X-rays images. However, DNNs are vulnerable to adversarial examples, which may cause misdiagnoses to patients when applying the DNN based methods in disease detection. Recently, there is few comprehensive studies exploring the influence of attack and defense methods on disease detection, especially for the multi-label classification problem. In this paper, we aim to review various adversarial attack and defense methods on chest X-rays. First, the motivations and the mathematical representations of …
California Institute of Technology（加州理工学院）；Beckman Center for Single-cell Profiling and Engineering（贝克曼单细胞分析与工程中心）
Sequencing costs currently prohibit the application of single-cell mRNA-seq to many biological and clinical analyses. Targeted single-cell mRNA-sequencing reduces sequencing costs by profiling reduced gene sets that capture biological information with a minimal number of genes. Here, we introduce an active learning method (ActiveSVM) that identifies minimal but highly-informative gene sets that enable the identification of cell-types, physiological states, and genetic perturbations in single-cell data using a small number of genes. Our active feature selection procedure generates minimal gene …
University of Edinburgh（爱丁堡大学）；The Alan Turing Institute（艾伦·图灵研究所）
Pseudo healthy synthesis, i.e. the creation of a subject-specific `healthy' image from a pathological one, could be helpful in tasks such as anomaly detection, understanding changes induced by pathology and disease or even as data augmentation. We treat this task as a factor decomposition problem: we aim to separate what appears to be healthy and where disease is (as a map). The two factors are then recombined (by a network) to reconstruct the input disease image. We train our models in an adversarial way using either paired or unpaired settings, where we pair disease images and maps (as segme…
Johns Hopkins University（约翰斯·霍普金斯大学）；Lieber Institute for Brain Development（利伯大脑发育研究所）；University of Bari Aldo Moro（巴里大学阿尔多·莫罗大学）；Azienda Ospedaliero-Universitaria Consorziale Policlinico（巴里大学联合综合医院）
We propose a novel deep neural network architecture to integrate imaging and genetics data, as guided by diagnosis, that provides interpretable biomarkers. Our model consists of an encoder, a decoder and a classifier. The encoder learns a non-linear subspace shared between the input data modalities. The classifier and the decoder act as regularizers to ensure that the low-dimensional encoding captures predictive differences between patients and controls. We use a learnable dropout layer to extract interpretable biomarkers from the data, and our unique training strategy can easily accommodate m…
A multi-locus predictiveness curve and its summary assessment for genetic risk prediction
Michigan State University（密歇根州立大学）；University of North Texas Health Science Center（北德克萨斯大学健康科学中心）；Indiana University Bloomington（印第安纳大学伯明顿分校）；University of Auckland（奥克兰大学）；Hangzhou Normal University（杭州师范大学）
Cancer is responsible for millions of deaths worldwide every year. Although significant progress hasbeen achieved in cancer medicine, many issues remain to be addressed for improving cancer therapy.Appropriate cancer patient stratification is the prerequisite for selecting appropriate treatment plan, ascancer patients are of known heterogeneous genetic make-ups and phenotypic differences. In thisstudy, built upon deep phenotypic characterizations extractable from Mayo Clinic electronic healthrecords (EHRs) and genetic test reports for a collection of cancer patients, we evaluated variousgraph …
In recent years, people from all over the world are suffering from one of the most severe diseases in history, known as Coronavirus disease 2019, COVID-19 for short. When the virus reaches the lungs, it has a higher probability to cause lung pneumonia and sepsis. X-ray image is a powerful tool in identifying the typical features of the infection for COVID-19 patients. The radiologists and pathologists observe that ground-glass opacity appears in the chest X-ray for infected patient \cite{cozzi2021ground}, and it could be used as one of the criteria during the diagnosis process. In the past few…
Explainability-Driven Leaf Disease Classification Using Adversarial Training and Knowledge Distillation
National University of Science and Technology POLITEHNICA Bucharest（布加勒斯特国立科技理工大学）；National Institute for Research and Development in Informatics - ICI Bucharest（罗马尼亚国家信息研究与发展研究所（ICI布加勒斯特））；Academy of Romanian Scientists（罗马尼亚科学家学院）
Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences（中国科学院深圳先进技术研究院）；Shenzhen University（深圳大学）；Renmin University of China（中国人民大学）；Central South University（中南大学）
Alzheimer's disease is characterized by alterations of the brain's structural and functional connectivity during its progressive degenerative processes. Existing auxiliary diagnostic methods have accomplished the classification task, but few of them can accurately evaluate the changing characteristics of brain connectivity. In this work, a prior guided adversarial representation learning and hypergraph perceptual network (PGARL-HPN) is proposed to predict abnormal brain connections using triple-modality medical images. Concretely, a prior distribution from the anatomical knowledge is estimated…
Functional Analysis of Variance for Association Studies
Michigan State University（密歇根州立大学）；National Institute of Environmental Health Sciences（国家环境健康科学研究所）；National Institutes of Health（美国国立卫生研究院）；Montana State University（蒙大拿州立大学）
University of Edinburgh（爱丁堡大学）；The Alan Turing Institute（艾伦·图灵研究所）
Due to the limited availability of medical data, deep learning approaches for medical image analysis tend to generalise poorly to unseen data. Augmenting data during training with random transformations has been shown to help and became a ubiquitous technique for training neural networks. Here, we propose a novel adversarial counterfactual augmentation scheme that aims at finding the most \textit{effective} synthesised images to improve downstream tasks, given a pre-trained generative model. Specifically, we construct an adversarial game where we update the input \textit{conditional factor} of…
Medical imaging AI systems such as disease classification and segmentation are increasingly inspired and transformed from computer vision based AI systems. Although an array of adversarial training and/or loss function based defense techniques have been developed and proved to be effective in computer vision, defending against adversarial attacks on medical images remains largely an uncharted territory due to the following unique challenges: 1) label scarcity in medical images significantly limits adversarial generalizability of the AI system; 2) vastly similar and dominant fore- and backgroun…
