Network Modeling and Analysis in Health Informatics and Bioinformatics最新文献

Since December 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has affected almost all countries. The unprecedented spreading of this virus has led to the insurgence of many variants that impact protein sequence and structure that need continuous monitoring and analysis of the sequences to understand the genetic evolution and to prevent possible dangerous outcomes. Some variants causing the modification of the structure of the proteins, such as the Spike protein S, need to be monitored. Protein contact networks (PCNs) have been recently proposed as a modelling framework for protein structures. In such a framework, the protein structure is represented as an unweighted graph whose nodes are the central atoms of the backbones (C- $\alpha$ ), and edges connect two atoms falling in the spatial distance between 4 and 7 Å. PCN may also be a data-rich representation since we may add to each node/atom biological and topological information. Such formalism enables the possibility of using algorithms from graph theory to analyze the graph. In particular, we refer to graph embedding methods enabling the analysis of such graphs with deep learning methods. In this work, we explore the possibility of embedding PCN using Graph Neural Networks and then analyze in the embedded space each residue to distinguish mutated residues from non-mutated ones. In particular, we analyzed the structure of the Spike protein of the coronavirus. First, we obtained the PCNs of the Spike protein for the wild-type, $\alpha$ , $\beta$ , and $\delta$ variants. Then we used the GraphSage embedding algorithm to obtain an unsupervised embedding. Then we analyzed the point of mutation in the embedded space. Results show the characteristics of the mutation point in the embedding space.

Much research has been done on the efficacy of vaccines against the COVID-19 pandemic, but the claims have not yet been realized in the real world. This paper proposes three COVID-19 policy outcome analysis tools such as jpscore for scoring and revealing the best prefecture policy in Japan, scorecovid for scoring and revealing the best country policy in the world, and finally hiscovid for visualizing and identifying when policymakers made mistakes in time-series scores. Poorly scored countries or prefectures can learn good strategies from the best country or prefecture with excellent scores. Three tools are based on a single metric dividing the number of COVID-19 deaths by the population in millions. Three tools suggest us that the sustainable mandatory test-isolation strategy should be adopted in the world for mitigating the pandemic. This paper also addresses what is lacking in Japan for scientific evidence-based research for mitigating the pandemic. Visualization tools and sorted and time-series scores of policy outcomes help policymakers make the right decisions.

Responding to the pandemic caused by SARS-CoV-2, the scientific community intensified efforts to provide drugs effective against the virus. To strengthen these efforts, the "COVID Moonshot" project has been accepting public suggestions for computationally triaged, synthesized, and tested molecules. The project aimed to identify molecules of low molecular weight with activity against the virus, for oral treatment. The ability of a drug to cross the intestinal cell membranes and enter circulation decisively influences its bioavailability, and hence the need to optimize permeability in the early stages of drug discovery. In our present work, as a contribution to the ongoing scientific efforts, we employed artificial neural network algorithms to develop QSAR tools for modelling the PAMPA effective permeability (passive diffusion) of orally administered drugs. We identified a set of 61 features most relevant in explaining drug cell permeability and used them to develop a stacked regression ensemble model, subsequently used to predict the permeability of molecules included in datasets made available through the COVID Moonshot project. Our model was shown to be robust and may provide a promising framework for predicting the potential permeability of molecules not yet synthesized, thus guiding the process of drug design.

Supplementary information: The online version contains supplementary material available at 10.1007/s13721-023-00410-9.

Community-acquired pneumonia is primarily caused by Streptococcus pneumoniae and Klebsiella pneumoniae, two pathogens that have high morbidity and mortality rates. This is largely due to bacterial resistance development against current antibiotics and the lack of effective vaccines. The objective of this work was to develop an immunogenic multi-epitope subunit vaccine capable of eliciting a robust immune response against S. pneumoniae and K. pneumoniae. The targeted proteins were the pneumococcal surface proteins (PspA and PspC) and choline-binding protein (CbpA) of S. pneumoniae and the outer membrane proteins (OmpA and OmpW) of K. pneumoniae. Different computational approaches and various immune filters were employed for designing a vaccine. The immunogenicity and safety of the vaccine were evaluated by utilizing many physicochemical and antigenic profiles. To improve structural stability, disulfide engineering was applied to a portion of the vaccine structure with high mobility. Molecular docking was performed to examine the binding affinities and biological interactions at the atomic level between the vaccine and Toll-like receptors (TLR2 and 4). Further, the dynamic stabilities of the vaccine and TLRs complexes were investigated by molecular dynamics simulations. While the immune response induction capability of the vaccine was assessed by the immune simulation study. Vaccine translation and expression efficiency was determined through an in silico cloning experiment utilizing the pET28a(+) plasmid vector. The obtained results revealed that the designed vaccine is structurally stable and able to generate an effective immune response to combat pneumococcal infection.

Supplementary information: The online version contains supplementary material available at 10.1007/s13721-023-00416-3.

Integration of mobile health (mHealth) applications (apps) into chronic lung disease management is becoming increasingly popular. MHealth apps may support adoption of self-management behaviors to assist people in symptoms control and quality of life enhancement. However, mHealth apps' designs, features, and content are inconsistently reported, making it difficult to determine which were the effective components. Therefore, this review aims to summarize the characteristics and features of published mHealth apps for chronic lung diseases. A structured search strategy across five databases (CINAHL, Medline, Embase, Scopus and Cochrane) was performed. Randomized controlled trials investigating interactive mHealth apps in adults with chronic lung disease were included. Screening and full-text reviews were completed by three reviewers using Research Screener and Covidence. Data extraction followed the mHealth Index and Navigation Database (MIND) Evaluation Framework (https://mindapps.org/), a tool designed to help clinicians determine the best mHealth apps to address patients' needs. Over 90,000 articles were screened, with 16 papers included. Fifteen distinct apps were identified, 8 for chronic obstructive pulmonary disease (53%) and 7 for asthma (46%) self-management. Different resources informed app design approaches, accompanied with varying qualities and features across studies. Common reported features included symptom tracking, medication reminders, education, and clinical support. There was insufficient information to answer MIND questions regarding security and privacy, and only five apps had additional publications to support their clinical foundation. Current studies reported designs and features of self-management apps differently. These app design variations create challenges in determining their effectiveness and suitability for chronic lung disease self-management. Registration: PROSPERO (CRD42021260205).

Supplementary information: The online version contains supplementary material available at 10.1007/s13721-023-00419-0.

Network-based models are apt for understanding epidemic dynamics due to their inherent ability to model the heterogeneity of interactions in the contemporary world of intense human connectivity. We propose a framework to create a wire-frame that mimics the social contact network of the population in a geography by lacing it with demographic information. The framework results in a modular network with small-world topology that accommodates density variations and emulates human interactions in family, social, and work spaces. When loaded with suitable economic, social, and urban data shaping patterns of human connectance, the network emerges as a potent decision-making instrument for urban planners, demographers, and social scientists. We employ synthetic networks to experiment in a controlled environment and study the impact of zoning, density variations, and population mobility on the epidemic variables using a variant of the SEIR model. Our results reveal that these demographic factors have a characteristic influence on social contact patterns, manifesting as distinct epidemic dynamics. Subsequently, we present a real-world COVID-19 case study for three Indian states by creating corresponding surrogate social contact networks using available census data. The case study validates that the demography-laced modular contact network reduces errors in the estimates of epidemic variables.

Malaria is a vector-borne disease that poses major health challenges globally, with the highest burden in children less than 5 years old. Prevention and treatment have been the main interventions measures until the recent groundbreaking highly recommended malaria vaccine by WHO for children below five. A two-group malaria model structured by age with vaccination of individuals aged below 5 years old is formulated and theoretically analyzed. The disease-free equilibrium is globally asymptotically stable when the disease-induced death rate in both human groups is zero. Descarte's rule of signs is used to discuss the possible existence of multiple endemic equilibria. By construction, mathematical models inherit the loss of information that could make prediction of model outcomes imprecise. Thus, a global sensitivity analysis of the basic reproduction number and the vaccination class as response functions using Latin-Hypercube Sampling in combination with partial rank correlation coefficient are graphically depicted. As expected, the most sensitive parameters are related to children under 5 years old. Through the application of optimal control theory, the best combination of interventions measures to mitigate the spread of malaria is investigated. Simulations results show that concurrently applying the three intervention measures, namely: personal protection, treatment, and vaccination of childreen under-five is the best strategy for fighting against malaria epidemic in a community, relative to using either single or any dual combination of intervention(s) at a time.