Elucidating immunological characteristics of the adenoma-carcinoma sequence in colorectal cancer patients in South Korea using a bioinformatics approach.

Colorectal cancer (CRC) is one of the top five most common and life-threatening malignancies worldwide. Most CRC develops from advanced colorectal adenoma (ACA), a precancerous stage, through the adenoma-carcinoma sequence. However, its underlying mechanisms, including how the tumor microenvironment changes, remain elusive. Therefore, we conducted an integrative analysis comparing RNA-seq data collected from 40 ACA patients who visited Dongguk University Ilsan Hospital with normal adjacent colons and tumor samples from 18 CRC patients collected from a public database. Differential expression analysis identified 21 and 79 sequentially up- or down-regulated genes across the continuum, respectively. The functional centrality of the continuum genes was assessed through network analysis, identifying 11 up- and 13 down-regulated hub-genes. Subsequently, we validated the prognostic effects of hub-genes using the Kaplan-Meier survival analysis. To estimate the immunological transition of the adenoma-carcinoma sequence, single-cell deconvolution and immune repertoire analyses were conducted. Significant composition changes for innate immunity cells and decreased plasma B-cells with immunoglobulin diversity were observed, along with distinctive immunoglobulin recombination patterns. Taken together, we believe our findings suggest underlying transcriptional and immunological changes during the adenoma-carcinoma sequence, contributing to the further development of pre-diagnostic markers for CRC.

Prioritizing susceptibility genes for the prognosis of male-pattern baldness with transcriptome-wide association study.

BACKGROUND: Male-pattern baldness (MPB) is the most common cause of hair loss in men. It can be categorized into three types: type 2 (T2), type 3 (T3), and type 4 (T4), with type 1 (T1) being considered normal. Although various MPB-associated genetic variants have been suggested, a comprehensive study for linking these variants to gene expression regulation has not been performed to the best of our knowledge. RESULTS: In this study, we prioritized MPB-related tissue panels using tissue-specific enrichment analysis and utilized single-tissue panels from genotype-tissue expression version 8, as well as cross-tissue panels from context-specific genetics. Through a transcriptome-wide association study and colocalization analysis, we identified 52, 75, and 144 MPB associations for T2, T3, and T4, respectively. To assess the causality of MPB genes, we performed a conditional and joint analysis, which revealed 10, 11, and 54 putative causality genes for T2, T3, and T4, respectively. Finally, we conducted drug repositioning and identified potential drug candidates that are connected to MPB-associated genes. CONCLUSIONS: Overall, through an integrative analysis of gene expression and genotype data, we have identified robust MPB susceptibility genes that may help uncover the underlying molecular mechanisms and the novel drug candidates that may alleviate MPB.

Large-scale integrative analysis of juvenile idiopathic arthritis for new insight into its pathogenesis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is one of the most prevalent rheumatic disorders in children and is classified as an autoimmune disease (AID). While a robust genetic contribution to JIA etiology has been established, the exact pathogenesis remains unclear. METHODS: To prioritize biologically interpretable susceptibility genes and proteins for JIA, we conducted transcriptome-wide and proteome-wide association studies (TWAS/PWAS). Then, to understand the genetic architecture of JIA, we systematically analyzed single-nucleotide polymorphism (SNP)-based heritability, a signature of natural selection, and polygenicity. Next, we conducted HLA typing using multi-ethnicity RNA sequencing data. Additionally, we examined the T cell receptor (TCR) repertoire at a single-cell level to explore the potential links between immunity and JIA risk. RESULTS: We have identified 19 TWAS genes and two PWAS proteins associated with JIA risks. Furthermore, we observe that the heritability and cell type enrichment analysis of JIA are enriched in T lymphocytes and HLA regions and that JIA shows higher polygenicity compared to other AIDs. In multi-ancestry HLA typing, B*45:01 is more prevalent in African JIA patients than in European JIA patients, whereas DQA1*01:01, DQA1*03:01, and DRB1*04:01 exhibit a higher frequency in European JIA patients. Using single-cell immune repertoire analysis, we identify clonally expanded T cell subpopulations in JIA patients, including CXCL13+BHLHE40+ TH cells which are significantly associated with JIA risks. CONCLUSION: Our findings shed new light on the pathogenesis of JIA and provide a strong foundation for future mechanistic studies aimed at uncovering the molecular drivers of JIA.

Towards Semantic Smart Cities: A Study on the Conceptualization and Implementation of Semantic Context Inference Systems.

Smart cities provide integrated management and operation of urban data emerging within a city, supplying the infrastructure for smart city services and resolving various urban challenges. Nevertheless, cities continue to grapple with substantial issues, such as contagious diseases and terrorism, that pose severe financial and human risks. These problems sporadically arise in various locales, and current smart city frameworks lack the capability to autonomously identify and address these issues. The challenge intensifies especially when trying to recognize and respond to unprecedented problems. The primary objective of this research is to predict potential urban issues and support their resolution proactively. To achieve this, our system makes use of semantic reasoning to understand the ongoing situations within the city. In this process, the 5W1H principles serve as inference rules, guiding the extraction and consolidation of context. Firstly, utilizing domain-specific annotation templates, we craft a semantic graph by amalgamating information from various sources available in the city, such as municipal public data and IoT platforms. Subsequently, the system autonomously infers and accumulates contexts of situations occurring in the city using 5W1H-based reasoning. As a result, the accumulated contexts allow for inferring potential urban problems by identifying repeated disruptions in city services at specific times or locations and establishing connections among them. The main contribution of this paper lies in proposing a comprehensive conceptual model for the suggested system and presenting actual implementation cases and applicable use cases. These contributions facilitate awareness among city administrators and citizens within a smart city regarding potential problem-prone areas or times, thereby aiding in the preemptive identification and mitigation of urban challenges.

Meta-analysis of single-cell RNA-sequencing data for depicting the transcriptomic landscape of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a respiratory disease characterized by airflow limitation and chronic inflammation of the lungs that is a leading cause of death worldwide. Since the complete pathological mechanisms at the single-cell level are not fully understood yet, an integrative approach to characterizing the single-cell-resolution landscape of COPD is required. To identify the cell types and mechanisms associated with the development of COPD, we conducted a meta-analysis using three single-cell RNA-sequencing datasets of COPD. Among the 154,011 cells from 16 COPD patients and 18 healthy subjects, 17 distinct cell types were observed. Of the 17 cell types, monocytes, mast cells, and alveolar type 2 cells (AT2 cells) were found to be etiologically implicated in COPD based on genetic and transcriptomic features. The most transcriptomically diversified states of the three etiological cell types showed significant enrichment in immune/inflammatory responses (monocytes and mast cells) and/or mitochondrial dysfunction (monocytes and AT2 cells). We then identified three chemical candidates that may potentially induce COPD by modulating gene expression patterns in the three etiological cell types. Overall, our study suggests the single-cell level mechanisms underlying the pathogenesis of COPD and may provide information on toxic compounds that could be potential risk factors for COPD.

Transparent Rule Enablement Based on Commonization Approach in Heterogeneous IoT Edge Networks.

The paradigm of the Internet of Things (IoT) and edge computing brings a number of heterogeneous devices to the network edge for monitoring and controlling the environment. For reacting to events dynamically and automatically in the environment, rule-enabled IoT edge platforms operate the deployed service scenarios at the network edge, based on filtering events to perform control actions. However, due to the heterogeneity of the IoT edge networks, deploying a consistent rule context for operating a consistent rule scenario on multiple heterogeneous IoT edge platforms is difficult because of the difference in protocols and data formats. In this paper, we propose a transparent rule enablement, based on the commonization approach, for enabling a consistent rule scenario in heterogeneous IoT edge networks. The proposed IoT Edge Rule Agent Platform (IERAP) deploys device proxies to share consistent rules with IoT edge platforms without considering the difference in protocols and data formats. Therefore, each device proxy only considers the translation of the corresponding platform-specific and common formats. Also, the rules are deployed by the corresponding device proxy, which enables rules to be deployed to heterogeneous IoT edge platforms to perform the consistent rule scenario without considering the format and underlying protocols of the destination platform.

A Transcriptome-Wide Analysis of Psoriasis: Identifying the Potential Causal Genes and Drug Candidates.

Psoriasis is a chronic inflammatory skin disease characterized by cutaneous eruptions and pruritus. Because the genetic backgrounds of psoriasis are only partially revealed, an integrative and rigorous study is necessary. We conducted a transcriptome-wide association study (TWAS) with the new Genotype-Tissue Expression version 8 reference panels, including some tissue and multi-tissue panels that were not used previously. We performed tissue-specific heritability analyses on genome-wide association study data to prioritize the tissue panels for TWAS analysis. TWAS and colocalization (COLOC) analyses were performed with eight tissues from the single-tissue panels and the multi-tissue panels of context-specific genetics (CONTENT) to increase tissue specificity and statistical power. From TWAS, we identified the significant associations of 101 genes in the single-tissue panels and 64 genes in the multi-tissue panels, of which 26 genes were replicated in the COLOC. Functional annotation and network analyses identified that the genes were associated with psoriasis and/or immune responses. We also suggested drug candidates that interact with jointly significant genes through a conditional and joint analysis. Together, our findings may contribute to revealing the underlying genetic mechanisms and provide new insights into treatments for psoriasis.

A Survey on Air-Gap Attacks: Fundamentals, Transport Means, Attack Scenarios and Challenges.

Major public institutions and organizations that handle sensitive data frequently enforce strong security policies by implementing network separation policies that segregates their internal work networks and internet network using air gaps to prevent the leakage of confidential information. Such closed networks have long been considered the most secure technique for protecting data; however, studies have shown that they are no longer effective in providing a safe data protection environment. Research on air-gap attacks remains in its infancy stage. Studies have been conducted to check the method and demonstrate the possibility of transmitting data using various transmission media available within the closed network. These transmission media include optical signals such as HDD LEDs, acoustic signals such as speakers, and the electrical signals of power lines. This paper examines various media used for air-gap attacks by analyzing different techniques and their essential functions, strengths, and limitations. The findings of this survey and the follow-up analysis aim to assist companies and organizations in protecting their information by providing an understanding of air-gap attacks and their current trends.

A transcriptome-wide association study of uterine fibroids to identify potential genetic markers and toxic chemicals.

Uterine fibroid is one of the most prevalent benign tumors in women, with high socioeconomic costs. Although genome-wide association studies (GWAS) have identified several loci associated with uterine fibroid risks, they could not successfully interpret the biological effects of genomic variants at the gene expression levels. To prioritize uterine fibroid susceptibility genes that are biologically interpretable, we conducted a transcriptome-wide association study (TWAS) by integrating GWAS data of uterine fibroid and expression quantitative loci data. We identified nine significant TWAS genes including two novel genes, RP11-282O18.3 and KBTBD7, which may be causal genes for uterine fibroid. We conducted functional enrichment network analyses using the TWAS results to investigate the biological pathways in which the overall TWAS genes were involved. The results demonstrated the immune system process to be a key pathway in uterine fibroid pathogenesis. Finally, we carried out chemical-gene interaction analyses using the TWAS results and the comparative toxicogenomics database to determine the potential risk chemicals for uterine fibroid. We identified five toxic chemicals that were significantly associated with uterine fibroid TWAS genes, suggesting that they may be implicated in the pathogenesis of uterine fibroid. In this study, we performed an integrative analysis covering the broad application of bioinformatics approaches. Our study may provide a deeper understanding of uterine fibroid etiologies and informative notifications about potential risk chemicals for uterine fibroid.

Toward Mapping an NGSI-LD Context Model on RDF Graph Approaches: A Comparison Study.

A considerable number of Internet of Things deployments are isolated from specific solutions, from devices to data platforms. Standardized data models were proposed to overcome the interoperability gap between these deployments. Next generation service interfaces-linked data (NGSI-LD) is one of the proposed platforms that exploits linked data and proposes an information model and an application programming interface (API) for easy use and standard management of context information. The NGSI-LD information model is based on JSON for Linked Data (JSON-LD) as a serialization format for context information. This efficiently exploits the potential of semantics and linked open data. However, the NGSI-LD graph API and query language are still theoretically defined and limited to some preliminary works. Consequently, current NGSI-LD implementations are mainly based on traditional databases, where the JSON-LD serialization is supported but not exploited owing to the difficulties in defining and implementing new NGSI-LD based Graph APIs. One of the basic solutions is the use of an RDF store for NGSI-LD payloads because these types of databases are well defined and maintained and will not need any added effort for JSON-LD based payloads. However, the main complication at this level is the use of reification to annotate relationships. This study focused on both aspects of exploiting the semantics of NGSI-LD by proposing standardized mapping mechanisms to RDF graphs without reifying JSON-LD payloads and with respect to the NGSI-LD context model and API. Our main proposals highlight that exploiting the RDF store for processing NGSI-LD data semantically is feasible and uncomplicated. We illustrated the proposed mapping approaches with real use-case examples and a possible exploitation of semantic approaches.

Integrative transcriptome-wide analysis of atopic dermatitis for drug repositioning.

Atopic dermatitis (AD) is one of the most common inflammatory skin diseases, which significantly impact the quality of life. Transcriptome-wide association study (TWAS) was conducted to estimate both transcriptomic and genomic features of AD and detected significant associations between 31 expression quantitative loci and 25 genes. Our results replicated well-known genetic markers for AD, as well as 4 novel associated genes. Next, transcriptome meta-analysis was conducted with 5 studies retrieved from public databases and identified 5 additional novel susceptibility genes for AD. Applying the connectivity map to the results from TWAS and meta-analysis, robustly enriched perturbations were identified and their chemical or functional properties were analyzed. Here, we report the first research on integrative approaches for an AD, combining TWAS and transcriptome meta-analysis. Together, our findings could provide a comprehensive understanding of the pathophysiologic mechanisms of AD and suggest potential drug candidates as alternative treatment options.

IoT-Enabled Smart Cities: Evolution and Outlook.

For the last decade the Smart City concept has been under development, fostered by the growing urbanization of the world's population and the need to handle the challenges that such a scenario raises. During this time many Smart City projects have been executed-some as proof-of-concept, but a growing number resulting in permanent, production-level deployments, improving the operation of the city and the quality of life of its citizens. Thus, Smart Cities are still a highly relevant paradigm which needs further development before it reaches its full potential and provides robust and resilient solutions. In this paper, the focus is set on the Internet of Things (IoT) as an enabling technology for the Smart City. In this sense, the paper reviews the current landscape of IoT-enabled Smart Cities, surveying relevant experiences and city initiatives that have embedded IoT within their city services and how they have generated an impact. The paper discusses the key technologies that have been developed and how they are contributing to the realization of the Smart City. Moreover, it presents some challenges that remain open ahead of us and which are the initiatives and technologies that are under development to tackle them.

An Integrative Transcriptome-Wide Analysis of Amyotrophic Lateral Sclerosis for the Identification of Potential Genetic Markers and Drug Candidates.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative neuromuscular disease. Although genome-wide association studies (GWAS) have successfully identified many variants significantly associated with ALS, it is still difficult to characterize the underlying biological mechanisms inducing ALS. In this study, we performed a transcriptome-wide association study (TWAS) to identify disease-specific genes in ALS. Using the largest ALS GWAS summary statistic (n = 80,610), we identified seven novel genes using 19 tissue reference panels. We conducted a conditional analysis to verify the genes' independence and to confirm that they are driven by genetically regulated expressions. Furthermore, we performed a TWAS-based enrichment analysis to highlight the association of important biological pathways, one in each of the four tissue reference panels. Finally, utilizing a connectivity map, a database of human cell expression profiles cultured with bioactive small molecules, we discovered functional associations between genes and drugs to identify 15 bioactive small molecules as potential drug candidates for ALS. We believe that, by integrating the largest ALS GWAS summary statistic with gene expression to identify new risk loci and causal genes, our study provides strong candidates for molecular basis experiments in ALS.

An Integrative Transcriptomic Analysis of Systemic Juvenile Idiopathic Arthritis for Identifying Potential Genetic Markers and Drug Candidates.

Systemic juvenile idiopathic arthritis (sJIA) is a rare subtype of juvenile idiopathic arthritis, whose clinical features are systemic fever and rash accompanied by painful joints and inflammation. Even though sJIA has been reported to be an autoinflammatory disorder, its exact pathogenesis remains unclear. In this study, we integrated a meta-analysis with a weighted gene co-expression network analysis (WGCNA) using 5 microarray datasets and an RNA sequencing dataset to understand the interconnection of susceptibility genes for sJIA. Using the integrative analysis, we identified a robust sJIA signature that consisted of 2 co-expressed gene sets comprising 103 up-regulated genes and 25 down-regulated genes in sJIA patients compared with healthy controls. Among the 128 sJIA signature genes, we identified an up-regulated cluster of 11 genes and a down-regulated cluster of 4 genes, which may play key roles in the pathogenesis of sJIA. We then detected 10 bioactive molecules targeting the significant gene clusters as potential novel drug candidates for sJIA using an in silico drug repositioning analysis. These findings suggest that the gene clusters may be potential genetic markers of sJIA and 10 drug candidates can contribute to the development of new therapeutic options for sJIA.

Harnessing the Power of Smart and Connected Health to Tackle COVID-19: IoT, AI, Robotics, and Blockchain for a Better World.

As COVID-19 hounds the world, the common cause of finding a swift solution to manage the pandemic has brought together researchers, institutions, governments, and society at large. The Internet of Things (IoT), artificial intelligence (AI)-including machine learning (ML) and Big Data analytics-as well as Robotics and Blockchain, are the four decisive areas of technological innovation that have been ingenuity harnessed to fight this pandemic and future ones. While these highly interrelated smart and connected health technologies cannot resolve the pandemic overnight and may not be the only answer to the crisis, they can provide greater insight into the disease and support frontline efforts to prevent and control the pandemic. This article provides a blend of discussions on the contribution of these digital technologies, propose several complementary and multidisciplinary techniques to combat COVID-19, offer opportunities for more holistic studies, and accelerate knowledge acquisition and scientific discoveries in pandemic research. First, four areas, where IoT can contribute are discussed, namely: 1) tracking and tracing; 2) remote patient monitoring (RPM) by wearable IoT (WIoT); 3) personal digital twins (PDTs); and 4) real-life use case: ICT/IoT solution in South Korea. Second, the role and novel applications of AI are explained, namely: 1) diagnosis and prognosis; 2) risk prediction; 3) vaccine and drug development; 4) research data set; 5) early warnings and alerts; 6) social control and fake news detection; and 7) communication and chatbot. Third, the main uses of robotics and drone technology are analyzed, including: 1) crowd surveillance; 2) public announcements; 3) screening and diagnosis; and 4) essential supply delivery. Finally, we discuss how distributed ledger technologies (DLTs), of which blockchain is a common example, can be combined with other technologies for tackling COVID-19.

Software-Defined Vehicular Cloud Networks: Architecture, Applications and Virtual Machine Migration.

Cloud computing supports many unprecedented cloud-based vehicular applications. To improve connectivity and bandwidth through programmable networking architectures, Software-Defined (SD) Vehicular Network (SDVN) is introduced. SDVN architecture enables vehicles to be equipped with SDN OpenFlow switch on which the routing rules are updated from a SDN OpenFlow controller. From SDVN, new vehicular architectures are introduced, for instance SD Vehicular Cloud (SDVC). In SDVC, vehicles are SDN devices that host virtualization technology for enabling deployment of cloud-based vehicular applications. In addition, the migration of Virtual Machines (VM) over SDVC challenges the performance of cloud-based vehicular applications due the highly mobility of vehicles. However, the current literature that discusses VM migration in SDVC is very limited. In this paper, we first analyze the evolution of computation and networking technologies of SDVC with a focus on its architecture within the cloud-based vehicular environment. Then, we discuss the potential cloud-based vehicular applications assisted by the SDVC along with its ability to manage several VM migration scenarios. Lastly, we provide a detailed comparison of existing frameworks in SDVC that integrate the VM migration approach and different emulators or simulators network used to evaluate VM frameworks' use cases.

Hy-Bridge: A Hybrid Blockchain for Privacy-Preserving and Trustful Energy Transactions in Internet-of-Things Platforms.

In the current centralized IoT ecosystems, all financial transactions are routed through IoT platform providers. The security and privacy issues are inevitable with an untrusted or compromised IoT platform provider. To address these issues, we propose Hy-Bridge, a hybrid blockchain-based billing and charging framework. In Hy-Bridge, the IoT platform provider plays no proxy role, and IoT users can securely and efficiently share a credit with other users. The trustful end-to-end functionality of blockchain helps us to provide accountability and reliability features in IoT transactions. Furthermore, with the blockchain-distributed consensus, we provide a credit-sharing feature for IoT users in the energy and utility market. To provide this feature, we introduce a local block framework for service management in the credit-sharing group. To preserve the IoT users' privacy and avoid any information leakage to the main blockchain, an interconnection position, called bridge, is introduced to isolate IoT users' peer-to-peer transactions and link the main blockchain to its subnetwork blockchain(s) in a hybrid model. To this end, a k-anonymity protection is performed on the bridge. To evaluate the performance of the introduced hybrid blockchain-based billing and charging, we simulated the energy use case scenario using Hy-Bridge. Our simulation results show that Hy-Bridge could protect user privacy with an acceptable level of information loss and CPU and memory usage.

Meta-Analysis of Polymyositis and Dermatomyositis Microarray Data Reveals Novel Genetic Biomarkers.

Polymyositis (PM) and dermatomyositis (DM) are both classified as idiopathic inflammatory myopathies. They share a few common characteristics such as inflammation and muscle weakness. Previous studies have indicated that these diseases present aspects of an auto-immune disorder; however, their exact pathogenesis is still unclear. In this study, three gene expression datasets (PM: 7, DM: 50, Control: 13) available in public databases were used to conduct meta-analysis. We then conducted expression quantitative trait loci analysis to detect the variant sites that may contribute to the pathogenesis of PM and DM. Six-hundred differentially expressed genes were identified in the meta-analysis (false discovery rate (FDR) < 0.01), among which 317 genes were up-regulated and 283 were down-regulated in the disease group compared with those in the healthy control group. The up-regulated genes were significantly enriched in interferon-signaling pathways in protein secretion, and/or in unfolded-protein response. We detected 10 single nucleotide polymorphisms (SNPs) which could potentially play key roles in driving the PM and DM. Along with previously reported genes, we identified 4 novel genes and 10 SNP-variant regions which could be used as candidates for potential drug targets or biomarkers for PM and DM.

Implementation of Sensing and Actuation Capabilities for IoT Devices Using oneM2M Platforms.

In this paper, we present an implementation work of sensing and actuation capabilities for IoT devices using the oneM2M standard-based platforms. We mainly focus on the heterogeneity of the hardware interfaces employed in IoT devices. For IoT devices (i.e., Internet-connected embedded systems) to perform sensing and actuation capabilities in a standardized manner, a well-designed middleware solution will be a crucial part of IoT platform. Accordingly, we propose an oneM2M standard-based IoT platform (called nCube) incorporated with a set of tiny middleware programs (called TAS) responsible for translating sensing values and actuation commands into oneM2M-defined resources accessible in Web-based applications. All the source codes for the oneM2M middleware platform and smartphone application are available for free in the GitHub repositories. The full details on the implementation work and open-source contributions are described.

Fabrication of Microarrays for the Analysis of Serological Antibody Isotypes against Food Antigens.

Food intolerance is delayed adverse food reactions which follow consumption of specific foods. The underlying mechanisms are not well understood, but food intolerance is often considered as a type 2 hypersensitivity reaction mediated by immunoglobulin G (IgG) antibody. To understand the causes of food intolerance, it is important to investigate sensitization patterns of food-specific IgGs (sIgG) in relation to dietary patterns and physical conditions. Conventional approaches to measure serological IgGs often require large volumes of serum, thus are not suitable for highly multiplexed assays. To overcome this impracticality, we developed a highly sensitive method to screen the sIgGs and other antibody isotypes against 66 antigens with minimal amount of serums. We prepared a microarray by immobilizing food antigens on activated glass slides. Human sera and their dietary information were obtained from 30 subjects. Aliquots (200 nl) of sera were analyzed against 66 food antigens in parallel. sIgG levels were determined and analyzed in relation to subjects' dietary patterns. The levels of antibody isotypes were also examined to understand the relationship between allergy and food intolerance. The developed microarray showed exceptional performances in antibody screening and demonstrated the potential to be used as an automated assay system.