In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan.

07:00 EST 13th February 2020 | BioPortfolio

Summary of "In-silico simulated prototype-patients using TPMS technology to study a potential adverse effect of sacubitril and valsartan."

Unveiling the mechanism of action of a drug is key to understand the benefits and adverse reactions of a medication in an organism. However, in complex diseases such as heart diseases there is not a unique mechanism of action but a wide range of different responses depending on the patient. Exploring this collection of mechanisms is one of the clues for a future personalized medicine. The Therapeutic Performance Mapping System (TPMS) is a Systems Biology approach that generates multiple models of the mechanism of action of a drug. Each molecular mechanism generated could be associated to particular individuals, here defined as prototype-patients, hence the generation of models using TPMS technology may be used for detecting adverse effects to specific patients. TPMS operates by (1) modelling the responses in humans with an accurate description of a protein network and (2) applying a Multilayer Perceptron-like and sampling strategy to find all plausible solutions. In the present study, TPMS is applied to explore the diversity of mechanisms of action of the drug combination sacubitril/valsartan. We use TPMS to generate a wide range of models explaining the relationship between sacubitril/valsartan and heart failure (the indication), as well as evaluating their association with macular degeneration (a potential adverse effect). Among the models generated, we identify a set of mechanisms of action associated to a better response in terms of heart failure treatment, which could also be associated to macular degeneration development. Finally, a set of 30 potential biomarkers are proposed to identify mechanisms (or prototype-patients) more prone of suffering macular degeneration when presenting good heart failure response. All prototype-patients models generated are completely theoretical and therefore they do not necessarily involve clinical effects in real patients. Data and accession to software are available at


Journal Details

This article was published in the following journal.

Name: PloS one
ISSN: 1932-6203
Pages: e0228926


DeepDyve research library

PubMed Articles [41436 Associated PubMed Articles listed on BioPortfolio]

"It's Not an Acting Job… Don't Underestimate What a Simulated Patient Does": A Qualitative Study Exploring the Perspectives of Simulated Patients in Health Professions Education.

Simulated patients (SPs) are individuals who have learned to realistically portray patient roles in health professional education. Program recommendations are increasing for simulation programs, and a...

Cromparative Dynamics of Tropomyosin in Vertebrates and Invertebrates.

Tropomyosin (Tpm) is an extended α-helical coiled-coil homodimer that regulates actinomyosin interactions in muscle. Molecular simulations of four Tpms, two from the vertebrate class Mammalia (rat an...

The molecular mechanism of muscle dysfunction associated with the R133W mutation in Tpm2.2.

Ghost muscle fibres reconstituted with myosin heads labeled with the fluorescent probe 1,5-IAEDANS were used for analysis of muscle fibre dysfunction associated with the R133W mutation in β-tropomyos...

The anisotropic elastic behavior of the widely-used triply-periodic minimal surface based scaffolds.

The Triple Periodic Minimal Surface (TPMS) has emerged as a new approach for producing open cell porous scaffolds for biomedical applications. However, different from the traditional scaffolds, the TP...

Use of simulated patients to assess hypertension case management at public healthcare facilities in South Africa.

Our study aims to evaluate hypertensive case management in South Africa's public health sector using simulated patients.

Clinical Trials [3044 Associated Clinical Trials listed on BioPortfolio]

Non-invasive Glucose Measurement With Raman Technology in Patients With Type 1 and Type 2 Diabetes

The study was established to collect data and reference measurements in order to establish calibration models for the Prototype 0.3

BioForte Technology for in Silico Identification of Candidates for a New Microbiome-based Therapeutics and Diagnostics

The goal of the project is to develop and validate the BioForte technology. Its main functionality should be to in silico determine candidates for novel microbiome-based therapeutics and d...

Effect of Physician Race and Gender on Simulated Patients' Ratings

The purpose of the study was to determine whether the race and gender of a simulated doctor affected analog patients' reported confidence and satisfaction in the simulated doctor's diagnos...

A Pharmacokinetic (PK) Study of ACH-0144471 Modified Release Prototype Formulations in Healthy Subjects

The purpose of this study is to evaluate and compare the plasma PK profiles of study drug, ACH-0144471, in healthy subjects after administration of a single dose of multiple ACH-0144471 pr...

Acute Exposure of Simulated Hypoxia on Cardiac Output

Randomized crossover trial in patients with Pulmonary Hypertension (PAH, CTEPH) to assess the acute response to simulated altitude (FIO2: 15.1% = equivalent to 2500m above sea level) on no...

Medical and Biotech [MESH] Definitions

The application of scientific knowledge or technology to pharmacy and the pharmaceutical industry. It includes methods, techniques, and instrumentation in the manufacture, preparation, compounding, dispensing, packaging, and storing of drugs and other preparations used in diagnostic and determinative procedures, and in the treatment of patients.

External decompression applied to the lower body. It is used to study orthostatic intolerance and the effects of gravitation and acceleration, to produce simulated hemorrhage in physiologic research, to assess cardiovascular function, and to reduce abdominal stress during childbirth.

A ubiquitous target SNARE protein that interacts with SYNTAXIN and SYNAPTOBREVIN. It is a core component of the machinery for intracellular MEMBRANE FUSION. The sequence contains 2 SNARE domains, one is the prototype for the Qb-SNARES, and the other is the prototype for the Qc-SNARES.

The application of scientific knowledge or technology to the field of radiology. The applications center mostly around x-ray or radioisotopes for diagnostic and therapeutic purposes but the technological applications of any radiation or radiologic procedure is within the scope of radiologic technology.

An office established to help Congress participate and plan for the consequences of uses of technology. It provided information on both the beneficial and adverse effects of technological applications. The Office of Technology Assessment closed on September 29, 1995.

Quick Search

DeepDyve research library

Relevant Topics

Pharmacy is the science and technique of preparing as well as dispensing drugs and medicines. It is a health profession that links health sciences with chemical sciences and aims to ensure the safe and effective use of pharmaceutical drugs. The scope of...

Cardiology is a specialty of internal medicine.  Cardiac electrophysiology : Study of the electrical properties and conduction diseases of the heart. Echocardiography : The use of ultrasound to study the mechanical function/physics of the h...

Searches Linking to this Article