mRNA Splicing-Mediated Gene Expression Regulation in Innate Immunity

At the heart of an inflammatory response lies a tightly regulated gene expression program. Perturbations to this finely tuned response can result in unchecked or inappropriately scaled inflammation, shifting the balance from protective to destructive immunity. A variety of post-transcriptional mechanisms play a role in the fine-tuning of an inflammatory gene expression program. One such mechanism involves unproductive RNA splicing, whereby alternative splicing can frameshift the transcript or introduce a premature termination codon (PTC). These effects render the transcript nonfunctional and/or subject it to nonsense-mediated decay. We observed such an event in Irf7, the master regulator of the type I interferon response. We found a single intron was consistently retained at a level much greater than other introns in the Irf7 transcript. In an effort to understand trans-acting factors that regulate this retention, we used RNA-antisense purification followed by mass spectrometry (RAP-MS) to identify the factor BUD13 as a highly enriched protein on Irf7 transcripts. Deficiency in BUD13 was associated with increased retention, decreased mature Irf7 transcript and protein levels, and consequently a dampened type I interferon response, which compromised the ability of BUD13-deficient macrophages to withstand vesicular stomatitis virus (VSV) infection. Beyond this intron retention event in Irf7, we identified a variety of other unproductive splicing events in a number of important genes involved with the innate immune response. This unproductive splicing was not restricted to intron retention events. For example, we identified a frequently used alternative splice site in the crucial murine antiviral response gene, oligoadenylate synthetase 1g (Oas1g) that led to both a frameshift and incorporation of a PTC. Genome editing was used to remove the alternative splice site in a macrophage cell line, which led to both increased Oas1g expression and improved viral clearance. We hypothesize these events exist as a means of mitigation for what might otherwise be an inappropriately scaled response. In doing so, they represent a previously underappreciated layer of gene expression regulation in innate immunity.</p

Image and Video Forensics

Nowadays, images and videos have become the main modalities of information being exchanged in everyday life, and their pervasiveness has led the image forensics community to question their reliability, integrity, confidentiality, and security. Multimedia contents are generated in many different ways through the use of consumer electronics and high-quality digital imaging devices, such as smartphones, digital cameras, tablets, and wearable and IoT devices. The ever-increasing convenience of image acquisition has facilitated instant distribution and sharing of digital images on digital social platforms, determining a great amount of exchange data. Moreover, the pervasiveness of powerful image editing tools has allowed the manipulation of digital images for malicious or criminal ends, up to the creation of synthesized images and videos with the use of deep learning techniques. In response to these threats, the multimedia forensics community has produced major research efforts regarding the identification of the source and the detection of manipulation. In all cases (e.g., forensic investigations, fake news debunking, information warfare, and cyberattacks) where images and videos serve as critical evidence, forensic technologies that help to determine the origin, authenticity, and integrity of multimedia content can become essential tools. This book aims to collect a diverse and complementary set of articles that demonstrate new developments and applications in image and video forensics to tackle new and serious challenges to ensure media authenticity

인공지능 보안

학위논문 (박사) -- 서울대학교 대학원 : 자연과학대학 협동과정 생물정보학전공, 2021. 2. 윤성로.With the development of machine learning (ML), expectations for artificial intelligence (AI) technologies have increased daily. In particular, deep neural networks have demonstrated outstanding performance in many fields. However, if a deep-learning (DL) model causes mispredictions or misclassifications, it can cause difficulty, owing to malicious external influences. This dissertation discusses DL security and privacy issues and proposes methodologies for security and privacy attacks. First, we reviewed security attacks and defenses from two aspects. Evasion attacks use adversarial examples to disrupt the classification process, and poisoning attacks compromise training by compromising the training data. Next, we reviewed attacks on privacy that can exploit exposed training data and defenses, including differential privacy and encryption. For adversarial DL, we study the problem of finding adversarial examples against ML-based portable document format (PDF) malware classifiers. We believe that our problem is more challenging than those against ML models for image processing, owing to the highly complex data structure of PDFs, compared with traditional image datasets, and the requirement that the infected PDF should exhibit malicious behavior without being detected. We propose an attack using generative adversarial networks that effectively generates evasive PDFs using a variational autoencoder robust against adversarial examples. For privacy in DL, we study the problem of avoiding sensitive data being misused and propose a privacy-preserving framework for deep neural networks. Our methods are based on generative models that preserve the privacy of sensitive data while maintaining a high prediction performance. Finally, we study the security aspect in biological domains to detect maliciousness in deoxyribonucleic acid sequences and watermarks to protect intellectual properties. In summary, the proposed DL models for security and privacy embrace a diversity of research by attempting actual attacks and defenses in various fields.인공지능 모델을 사용하기 위해서는 개인별 데이터 수집이 필수적이다. 반면 개인의 민감한 데이터가 유출되는 경우에는 프라이버시 침해의 소지가 있다. 인공지능 모델을 사용하는데 수집된 데이터가 외부에 유출되지 않도록 하거나, 익명화, 부호화 등의 보안 기법을 인공지능 모델에 적용하는 분야를 Private AI로 분류할 수 있다. 또한 인공지능 모델이 노출될 경우 지적 소유권이 무력화될 수 있는 문제점과, 악의적인 학습 데이터를 이용하여 인공지능 시스템을 오작동할 수 있고 이러한 인공지능 모델 자체에 대한 위협은 Secure AI로 분류할 수 있다. 본 논문에서는 학습 데이터에 대한 공격을 기반으로 신경망의 결손 사례를 보여준다. 기존의 AEs 연구들은 이미지를 기반으로 많은 연구가 진행되었다. 보다 복잡한 heterogenous한 PDF 데이터로 연구를 확장하여 generative 기반의 모델을 제안하여 공격 샘플을 생성하였다. 다음으로 이상 패턴을 보이는 샘플을 검출할 수 있는 DNA steganalysis 방어 모델을 제안한다. 마지막으로 개인 정보 보호를 위해 generative 모델 기반의 익명화 기법들을 제안한다. 요약하면 본 논문은 인공지능 모델을 활용한 공격 및 방어 알고리즘과 신경망을 활용하는데 발생되는 프라이버시 이슈를 해결할 수 있는 기계학습 알고리즘에 기반한 일련의 방법론을 제안한다.Abstract i List of Figures vi List of Tables xiii 1 Introduction 1 2 Background 6 2.1 Deep Learning: a brief overview . . . . . . . . . . . . . . . . . . . 6 2.2 Security Attacks on Deep Learning Models . . . . . . . . . . . . . 10 2.2.1 Evasion Attacks . . . . . . . . . . . . . . . . . . . . . . . 12 2.2.2 Poisoning Attack . . . . . . . . . . . . . . . . . . . . . . . 20 2.3 Defense Techniques Against Deep Learning Models . . . . . . . . . 26 2.3.1 Defense Techniques against Evasion Attacks . . . . . . . . 27 2.3.2 Defense against Poisoning Attacks . . . . . . . . . . . . . . 36 2.4 Privacy issues on Deep Learning Models . . . . . . . . . . . . . . . 38 2.4.1 Attacks on Privacy . . . . . . . . . . . . . . . . . . . . . . 39 2.4.2 Defenses Against Attacks on Privacy . . . . . . . . . . . . 40 3 Attacks on Deep Learning Models 47 3.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.1.1 Threat Model . . . . . . . . . . . . . . . . . . . . . . . . . 53 3.1.2 Portable Document Format (PDF) . . . . . . . . . . . . . . 55 3.1.3 PDF Malware Classifiers . . . . . . . . . . . . . . . . . . . 57 3.1.4 Evasion Attacks . . . . . . . . . . . . . . . . . . . . . . . 58 3.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 60 3.2.1 Feature Extraction . . . . . . . . . . . . . . . . . . . . . . 60 3.2.2 Feature Selection Process . . . . . . . . . . . . . . . . . . 61 3.2.3 Seed Selection for Mutation . . . . . . . . . . . . . . . . . 62 3.2.4 Evading Model . . . . . . . . . . . . . . . . . . . . . . . . 63 3.2.5 Model architecture . . . . . . . . . . . . . . . . . . . . . . 67 3.2.6 PDF Repacking and Verification . . . . . . . . . . . . . . . 67 3.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 68 3.3.1 Datasets and Model Training . . . . . . . . . . . . . . . . . 68 3.3.2 Target Classifiers . . . . . . . . . . . . . . . . . . . . . . . 71 3.3.3 CVEs for Various Types of PDF Malware . . . . . . . . . . 72 3.3.4 Malicious Signature . . . . . . . . . . . . . . . . . . . . . 72 3.3.5 AntiVirus Engines (VirusTotal) . . . . . . . . . . . . . . . 76 3.3.6 Feature Mutation Result for Contagio . . . . . . . . . . . . 76 3.3.7 Feature Mutation Result for CVEs . . . . . . . . . . . . . . 78 3.3.8 Malicious Signature Verification . . . . . . . . . . . . . . . 78 3.3.9 Evasion Speed . . . . . . . . . . . . . . . . . . . . . . . . 80 3.3.10 AntiVirus Engines (VirusTotal) Result . . . . . . . . . . . . 82 3.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 84 4 Defense on Deep Learning Models 88 4.1 Background . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 90 4.1.1 Message-Hiding Regions . . . . . . . . . . . . . . . . . . . 91 4.1.2 DNA Steganography . . . . . . . . . . . . . . . . . . . . . 92 4.1.3 Example of Message Hiding . . . . . . . . . . . . . . . . . 94 4.1.4 DNA Steganalysis . . . . . . . . . . . . . . . . . . . . . . 95 4.2 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 96 4.2.1 Notations . . . . . . . . . . . . . . . . . . . . . . . . . . . 98 4.2.2 Proposed Model Architecture . . . . . . . . . . . . . . . . 103 4.3 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 105 4.3.1 Experiment Setup . . . . . . . . . . . . . . . . . . . . . . . 105 4.3.2 Environment . . . . . . . . . . . . . . . . . . . . . . . . . 106 4.3.3 Dataset . . . . . . . . . . . . . . . . . . . . . . . . . . . . 107 4.3.4 Model Training . . . . . . . . . . . . . . . . . . . . . . . . 107 4.3.5 Message Hiding Procedure . . . . . . . . . . . . . . . . . . 108 4.3.6 Evaluation Procedure . . . . . . . . . . . . . . . . . . . . . 109 4.3.7 Performance Comparison . . . . . . . . . . . . . . . . . . . 109 4.3.8 Analyzing Malicious Code in DNA Sequences . . . . . . . 112 4.4 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 113 5 Privacy: Generative Models for Anonymizing Private Data 115 5.1 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 5.1.1 Notations . . . . . . . . . . . . . . . . . . . . . . . . . . . 119 5.1.2 Anonymization using GANs . . . . . . . . . . . . . . . . . 119 5.1.3 Security Principle of Anonymized GANs . . . . . . . . . . 123 5.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 5.2.1 Datasets . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125 5.2.2 Target Classifiers . . . . . . . . . . . . . . . . . . . . . . . 126 5.2.3 Model Training . . . . . . . . . . . . . . . . . . . . . . . . 126 5.2.4 Evaluation Process . . . . . . . . . . . . . . . . . . . . . . 126 5.2.5 Comparison to Differential Privacy . . . . . . . . . . . . . 128 5.2.6 Performance Comparison . . . . . . . . . . . . . . . . . . . 128 5.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 130 6 Privacy: Privacy-preserving Inference for Deep Learning Models 132 6.1 Methods . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 135 6.1.1 Motivation . . . . . . . . . . . . . . . . . . . . . . . . . . 135 6.1.2 Scenario . . . . . . . . . . . . . . . . . . . . . . . . . . . . 137 6.1.3 Deep Private Generation Framework . . . . . . . . . . . . . 137 6.1.4 Security Principle . . . . . . . . . . . . . . . . . . . . . . . 141 6.1.5 Threat to the Classifier . . . . . . . . . . . . . . . . . . . . 143 6.2 Results . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 6.2.1 Datasets . . . . . . . . . . . . . . . . . . . . . . . . . . . . 143 6.2.2 Experimental Process . . . . . . . . . . . . . . . . . . . . . 146 6.2.3 Target Classifiers . . . . . . . . . . . . . . . . . . . . . . . 147 6.2.4 Model Training . . . . . . . . . . . . . . . . . . . . . . . . 147 6.2.5 Model Evaluation . . . . . . . . . . . . . . . . . . . . . . . 149 6.2.6 Performance Comparison . . . . . . . . . . . . . . . . . . . 150 6.3 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 151 7 Conclusion 153 7.0.1 Limitations . . . . . . . . . . . . . . . . . . . . . . . . . . 154 7.0.2 Future Work . . . . . . . . . . . . . . . . . . . . . . . . . 155 Bibliography 157 Abstract in Korean 195Docto

Multimedia Forensics

This book is open access. Media forensics has never been more relevant to societal life. Not only media content represents an ever-increasing share of the data traveling on the net and the preferred communications means for most users, it has also become integral part of most innovative applications in the digital information ecosystem that serves various sectors of society, from the entertainment, to journalism, to politics. Undoubtedly, the advances in deep learning and computational imaging contributed significantly to this outcome. The underlying technologies that drive this trend, however, also pose a profound challenge in establishing trust in what we see, hear, and read, and make media content the preferred target of malicious attacks. In this new threat landscape powered by innovative imaging technologies and sophisticated tools, based on autoencoders and generative adversarial networks, this book fills an important gap. It presents a comprehensive review of state-of-the-art forensics capabilities that relate to media attribution, integrity and authenticity verification, and counter forensics. Its content is developed to provide practitioners, researchers, photo and video enthusiasts, and students a holistic view of the field

Characterization of Mechanisms That Mediate Cancer Metastatic Colonization

Metastatic disease is the major cause of death in all solid tumor cancers. Current therapeutic strategies fail to target metastasis as the genes and mechanisms that regulate this process remain poorly understood. Metastatic colonization is the final step of the metastatic cascade whereby cancer cells form a tumor at a distant site. This final step is the culmination of clonal evolution of cancer populations that results in a highly aggressive population with enhanced metastatic capacity and often presents clinically as numerous inoperable tumor nodules that lead to mortality. Characterization of the mechanisms that govern metastatic colonization at cellular and molecular levels is necessary for the prevention and treatment of metastatic disease in patients. The first half of this thesis presents work towards understanding mechanisms that mediate colorectal cancer colonization of the liver in order to guide novel therapeutic strategies. An in vivo large-scale RNAinterference screen was performed to identify genes required for liver colonization. Liver and red blood cell pyruvate kinase (PKLR) was identified as a driver of liver metastasis in experimental models. In patients, PKLR was found to be expressed at higher levels in liver metastases relative to primary colorectal cancer tumors and also overexpressed in the primary tumors of patients with metastatic disease. PKLR was found to promote cell survival in the tumor core and enhance survival during conditions of concurrent high cell density and low oxygen availability. Molecular studies revealed that PKL negatively regulates pyruvate kinase M2 (PKM2) enzymatic activity. By inhibiting cellular pyruvate kinase activity, PKLR allows for the diversion of metabolites towards glutathione generation—allowing for the maintenance of glutathione levels. Adequate glutathione levels appears critical for metastatic colonization as GCLC, the catalytic subunit of glutamatecysteine ligase and the rate-limiting enzyme for glutathione synthesis, was found to be similarly required for effective metastasis, associated in its expression with human liver metastatic progression, and could be therapeutically targeted to reduce metastatic colonization. These findings highlight the impact of metabolic regulation on cancer cell adaptation within the metastatic niche. The robust effects on liver metastatic colonization observed upon modulating this metabolic pathway suggest clinical potential for therapeutic targeting of PKLR or cellular glutathione synthesis in colorectal cancer. The second half of this thesis presents work towards an understanding of diversity generation in clonal populations as it benefits cancer evolution and metastatic colonization. Clonal human breast cancer subpopulations were isolated to allow for the identification of subpopulations that exhibit population-level phenotypic diversity. These high variability clonal subpopulations were found to be more proficient at metastatic colonization—consistent with a positive role for diversification capacity in cancer progression. Through single-cell RNA-sequencing, cell-to-cell transcript expression variability was identified as a defining feature of these subpopulations, extending to protein-level variability. Furthermore, spliceosomal machinery was identified as a gene set with high expression variability, suggesting a means by which variation could be transmitted to a global level. Engineered variable expression of the spliceosomal gene SNRNP40 promoted metastatic fitness, and this metastatic capacity was attributable to cells with low SNRNP40 expression. Clinically, low SNRNP40 expression is associated with metastatic relapse. These findings reveal that transcriptomic variability generation may serve as a mechanism by which cancer subpopulations achieve diversification of gene expression states, which allows for enhanced fitness under changing environmental pressures encountered during metastatic progression

Multimedia Forensics

This book is open access. Media forensics has never been more relevant to societal life. Not only media content represents an ever-increasing share of the data traveling on the net and the preferred communications means for most users, it has also become integral part of most innovative applications in the digital information ecosystem that serves various sectors of society, from the entertainment, to journalism, to politics. Undoubtedly, the advances in deep learning and computational imaging contributed significantly to this outcome. The underlying technologies that drive this trend, however, also pose a profound challenge in establishing trust in what we see, hear, and read, and make media content the preferred target of malicious attacks. In this new threat landscape powered by innovative imaging technologies and sophisticated tools, based on autoencoders and generative adversarial networks, this book fills an important gap. It presents a comprehensive review of state-of-the-art forensics capabilities that relate to media attribution, integrity and authenticity verification, and counter forensics. Its content is developed to provide practitioners, researchers, photo and video enthusiasts, and students a holistic view of the field