Development: Pharmacokinetics—Systems Biology in Health and Disease III

Author(s):  
Aleš Prokop ◽  
Seth Michelson
2020 ◽  
Vol 15 (5) ◽  
pp. 695-703 ◽  
Author(s):  
Jennifer A. Schaub ◽  
Habib Hamidi ◽  
Lalita Subramanian ◽  
Matthias Kretzler

The kidney is a complex organ responsible for maintaining multiple aspects of homeostasis in the human body. The combination of distinct, yet interrelated, molecular functions across different cell types make the delineation of factors associated with loss or decline in kidney function challenging. Consequently, there has been a paucity of new diagnostic markers and treatment options becoming available to clinicians and patients in managing kidney diseases. A systems biology approach to understanding the kidney leverages recent advances in computational technology and methods to integrate diverse sets of data. It has the potential to unravel the interplay of multiple genes, proteins, and molecular mechanisms that drive key functions in kidney health and disease. The emergence of large, detailed, multilevel biologic and clinical data from national databases, cohort studies, and trials now provide the critical pieces needed for meaningful application of systems biology approaches in nephrology. The purpose of this review is to provide an overview of the current state in the evolution of the field. Recent successes of systems biology to identify targeted therapies linked to mechanistic biomarkers in the kidney are described to emphasize the relevance to clinical care and the outlook for improving outcomes for patients with kidney diseases.


2020 ◽  
Vol 21 (4) ◽  
pp. 1539 ◽  
Author(s):  
Ciro De Luca ◽  
Anna Maria Colangelo ◽  
Assunta Virtuoso ◽  
Lilia Alberghina ◽  
Michele Papa

The synaptic cleft has been vastly investigated in the last decades, leading to a novel and fascinating model of the functional and structural modifications linked to synaptic transmission and brain processing. The classic neurocentric model encompassing the neuronal pre- and post-synaptic terminals partly explains the fine-tuned plastic modifications under both pathological and physiological circumstances. Recent experimental evidence has incontrovertibly added oligodendrocytes, astrocytes, and microglia as pivotal elements for synapse formation and remodeling (tripartite synapse) in both the developing and adult brain. Moreover, synaptic plasticity and its pathological counterpart (maladaptive plasticity) have shown a deep connection with other molecular elements of the extracellular matrix (ECM), once considered as a mere extracellular structural scaffold altogether with the cellular glue (i.e., glia). The ECM adds another level of complexity to the modern model of the synapse, particularly, for the long-term plasticity and circuit maintenance. This model, called tetrapartite synapse, can be further implemented by including the neurovascular unit (NVU) and the immune system. Although they were considered so far as tightly separated from the central nervous system (CNS) plasticity, at least in physiological conditions, recent evidence endorsed these elements as structural and paramount actors in synaptic plasticity. This scenario is, as far as speculations and evidence have shown, a consistent model for both adaptive and maladaptive plasticity. However, a comprehensive understanding of brain processes and circuitry complexity is still lacking. Here we propose that a better interpretation of the CNS complexity can be granted by a systems biology approach through the construction of predictive molecular models that enable to enlighten the regulatory logic of the complex molecular networks underlying brain function in health and disease, thus opening the way to more effective treatments.


2010 ◽  
Vol 27 ◽  
pp. S80
Author(s):  
I. Thiele ◽  
R. Fleming ◽  
O. Rolfsson ◽  
B. Palsson

2010 ◽  
Vol 26 (4) ◽  
pp. 302-309 ◽  
Author(s):  
Alan Huett ◽  
Gautam Goel ◽  
Ramnik J Xavier

2021 ◽  
Vol 3 (Supplement_2) ◽  
pp. ii1-ii1
Author(s):  
Niven Narain ◽  
Michael Kiebish ◽  
Vivek Vishnudas ◽  
Vladimir Tolstikov ◽  
Gregory Miller ◽  
...  

Abstract The past decade has been witness to an explosive proliferation of data analytics modalities, all seeking to unravel insight into large-scale data sets. Machine learning and AI methodologies now occupy a central role in analyses of data sets that range in nature from genomics, “omics”, clinical, real-world evidence, and demographic data. Despite advances in data analytics/machine learning, access to complex population level clinical and related datasets, translating information into actionable guidance in human health and disease remains a challenge. Interrogative Biology, a systems biology/AI platform generates an unbiased, data-informed network for identifying targets (disease drivers) and biomarkers for disease interception at the point of transition to dysregulation, preceding clinical phenotype. The data topology is enabled by a systematic acquisition and interrogation of longitudinal bio-samples of clinically annotated human matrices (e.g. blood, urine, saliva, tissues) subjected to comprehensive multi-omic (genomic, proteomics, lipidomics and metabolomics) profiling over time. The molecular profiles are integrated with clinical health information using Bayesian artificial intelligence analytics, bAIcis, to generate causal network maps of overall health. Differentials between “health” and “disease” network maps identifies drivers (targets and biomarkers) of disease and are rapidly validated in orthogonal wet-lab disease specific perturbed model systems. Target information imputed into the bAIcis framework can define therapeutic strategies including identification of existing drugs and bio-actives for corrective response. Using a combination of clinic based sampling and dried blood spot analysis for longitudinal dynamic monitoring of markers of health-disease status provides opportunity for proactive clinical management and intervention for corrective response in advance of major deterioration of health status. Taken together, the approach herein allows for health surveillance based on in-depth biological profiling of alterations in the patient narrative to guide treatment modalities and strategies in a longitudinal and dynamic manner to identify, track, intercept, and arrest human disease.


2014 ◽  
Vol 55 ◽  
pp. 43-60 ◽  
Author(s):  
Tuulia Hyötyläinen ◽  
Matej Orešič

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