Click here to read some interesting recently published papers from our community. If you have published an article in the field of in silico medicine, send it to us: we will include it in this section of the newsletter!
BMC Bioinformatics: Beyond the state of the art of reverse vaccinology: predicting vaccine efficacy with the universal immune system simulator for influenza
Giulia Russo et al
Abstract
When it was first introduced in 2000, reverse vaccinology was defined as an in silico approach that begins with the pathogen's genomic sequence. It concludes with a list of potential proteins with a possible, but not necessarily, list of peptide candidates that need to be experimentally confirmed for vaccine production. During the subsequent years, reverse vaccinology has dramatically changed: now it consists of a large number of bioinformatics tools and processes, namely subtractive proteomics, computational vaccinology, immunoinformatics, and in silico related procedures. However, the state of the art of reverse vaccinology still misses the ability to predict the efficacy of the proposed vaccine formulation. Here, we describe how to fill the gap by introducing an advanced immune system simulator that tests the efficacy of a vaccine formulation against the disease for which it has been designed. As a working example, we entirely apply this advanced reverse vaccinology approach to design and predict the efficacy of a potential vaccine formulation against influenza H5N1. Climate change and melting glaciers are critical due to reactivating frozen viruses and emerging new pandemics. H5N1 is one of the potential strains present in icy lakes that can raise a pandemic. Investigating structural antigen protein is the most profitable therapeutic pipeline to generate an effective vaccine against H5N1. In particular, we designed a multi-epitope vaccine based on predicted epitopes of hemagglutinin and neuraminidase proteins that potentially trigger B-cells, CD4, and CD8 T-cell immune responses. Antigenicity and toxicity of all predicted CTL, Helper T-lymphocytes, and B-cells epitopes were evaluated, and both antigenic and non-allergenic epitopes were selected. From the perspective of advanced reverse vaccinology, the Universal Immune System Simulator, an in silico trial computational framework, was applied to estimate vaccine efficacy using a cohort of 100 digital patients.
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Computational and Structural Biotechnology Journal: Moving forward through the in silico modeling of multiple sclerosis: Treatment layer implementation and validation
Avisa Maleki et al
Abstract
Multiple sclerosis is an autoimmune inflammatory disease that affects the central nervous system through chronic demyelination and loss of oligodendrocytes. Since the relapsing-remitting form is the most prevalent, relapse-reducing therapies are a primary choice for specialists. Universal Immune System Simulator is an agent-based model that simulates the human immune system dynamics under physiological conditions and during several diseases, including multiple sclerosis. In this work, we extended the UISS-MS disease layer by adding two new treatments, i.e., cladribine and ocrelizumab, to show that UISS-MS can be potentially used to predict the effects of any existing or newly designed treatment against multiple sclerosis. To retrospectively validate UISS-MS with ocrelizumab and cladribine, we extracted the clinical and MRI data from patients included in two clinical trials, thus creating specific cohorts of digital patients for predicting and validating the effects of the considered drugs. The obtained results mirror those of the clinical trials, demonstrating that UISS-MS can correctly simulate the mechanisms of action and outcomes of the treatments. The successful retrospective validation concurred to confirm that UISS-MS can be considered a digital twin solution to be used as a support system to inform clinical decisions and predict disease course and therapeutic response at a single patient level.
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Computer methods and programs in Biomedicine: Combined mechanistic modeling and machine-learning approaches in systems biology ā A systematic literature review
Anna Procopio et al
Abstract
Mechanistic-based Model simulations (MM) are an effective approach commonly employed, for research and learning purposes, to better investigate and understand the inherent behavior of biological systems. Recent advancements in modern technologies and the large availability of omics data allowed the application of Machine Learning (ML) techniques to different research fields, including systems biology. However, the availability of information regarding the analyzed biological context, sufficient experimental data, as well as the degree of computational complexity, represent some of the issues that both MMs and ML techniques could present individually. For this reason, recently, several studies suggest overcoming or significantly reducing these drawbacks by combining the above-mentioned two methods. In the wake of the growing interest in this hybrid analysis approach, with the present review, we want to systematically investigate the studies available in the scientific literature in which both MMs and ML have been combined to explain biological processes at genomics, proteomics, and metabolomics levels, or the behavior of entire cellular populations.
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Nature - Scientific reports: Impact of TAVR on coronary artery hemodynamics using clinical measurements and imageābased patientāspecific in silico modeling
Louis Garber et al
Abstract
In recent years, transcatheter aortic valve replacement (TAVR) has become the leading method for treating aortic stenosis. While the procedure has improved dramatically in the past decade, there are still uncertainties about the impact of TAVR on coronary blood flow. Recent research has indicated that negative coronary events after TAVR may be partially driven by impaired coronary blood flow dynamics. Furthermore, the current technologies to rapidly obtain non-invasive coronary blood flow data are relatively limited. Herein, we present a lumped parameter computational model to simulate coronary blood flow in the main arteries as well as a series of cardiovascular hemodynamic metrics. The model was designed to only use a few inputs parameters from echocardiography, computed tomography and a sphygmomanometer. The novel computational model was then validated and applied to 19 patients undergoing TAVR to examine the impact of the procedure on coronary blood flow in the left anterior descending (LAD) artery, left circumflex (LCX) artery and right coronary artery (RCA) and various global hemodynamics metrics. Based on our findings, the changes in coronary blood flow after TAVR varied and were subject specific (37% had increased flow in all three coronary arteries, 32% had decreased flow in all coronary arteries, and 31% had both increased and decreased flow in different coronary arteries). Additionally, valvular pressure gradient, left ventricle (LV) workload and maximum LV pressure decreased by 61.5%, 4.5% and 13.0% respectively, while mean arterial pressure and cardiac output increased by 6.9% and 9.9% after TAVR. By applying this proof-of-concept computational model, a series of hemodynamic metrics were generated non-invasively which can help to better understand the individual relationships between TAVR and mean and peak coronary flow rates. In the future, tools such as these may play a vital role by providing clinicians with rapid insight into various cardiac and coronary metrics, rendering the planning for TAVR and other cardiovascular procedures more personalized.
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