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A Blueprint for Identifying Phenotypes and Drug Targets in Complex Disorders with Empirical Dynamics

Madison S. Krieger, Joshua M. Moreau, Haiyu Zhang, May Chien, James L. Zehnder, Morgan Craig
2020 Patterns  
These successes suggest that this blueprint has broader applicability in understanding and treating complex disorders.  ...  One subject has atypical markers and may represent a rare phenotype. Our analyses support this contention, and also lend new evidence to a theory for the cause of this disorder.  ...  ACKNOWLEDGMENTS The authors are extremely grateful to Indiana Delsart for bibliographic support.  ... 
doi:10.1016/j.patter.2020.100138 pmid:33336196 pmcid:PMC7733879 fatcat:uhekkicdozf7dpauft5ud37rae

Ontology-Based Vaccine and Drug Adverse Event Representation and Theory-Guided Systematic Causal Network Analysis Toward Integrative Pharmacovigilance Research

Yongqun He
2016 Current Pharmacology Reports  
The OneNet Theory of Life treats the whole process of the life of an organism as a single complex and dynamic network (i.e., OneNet).  ...  Compared with controlled terminologies (e.g., MedDRA, CTCAE, and WHO-ART), the community-based Ontology of Adverse Events (OAEs) has many advantages in AE classifications.  ...  In a complex dynamic system, prior states will have an influence on present states [84] .  ... 
doi:10.1007/s40495-016-0055-0 pmid:27458549 pmcid:PMC4957564 fatcat:kgyrslkfb5huzir75mm5cv22my

Can a systems approach produce a better understanding of mood disorders?

Nick Plant
2017 Biochimica et Biophysica Acta - General Subjects  
However, in a systems network targeting approach, the combination is designed first, and then the relevant drugs identified.  ...  In addition, a systems approach is ideally placed to identify novel network targeting drugs [8] .  ... 
doi:10.1016/j.bbagen.2016.08.016 pmid:27565355 fatcat:yuseuywjprge3gwf32xzohuupe

Systems Pharmacology: An Overview [chapter]

Marc R. Birtwistle, Jens Hansen, James M. Gallo, Sreeharish Muppirisetty, Peter Man-Un Ung, Ravi Iyengar, Avner Schlessinger
2016 Systems Pharmacology and Pharmacodynamics  
Dynamic modeling and sensitivity analysis allow the identification of robust and fragile nodes within these modules to identify putative drug targets for single or combinatorial drug treatment.  ...  Systems pharmacology has evolved from a discipline that focuses on drug action at the organ level to a discipline that combines traditional pharmacokinetic and pharmacodynamic modeling with recent systems  ...  Although these dynamic processes can be analyzed semi-empirically in pharmacokinetic and pharmacodynamics studies, such analyses are not necessarily constrained by molecular details, and with the advent  ... 
doi:10.1007/978-3-319-44534-2_4 fatcat:hnkzgvppa5ehjcqj65vw43fily

Synthetic Biology and Personalized Medicine

K.K. Jain
2013 Medical Principles and Practice  
The potential of synthetic genome, using an expanded genetic code that is designed for specific drug synthesis as well as delivery and activation of the drug in vivo by a pathological signal, was already  ...  Methods based on synthetic biology enable the design of novel strategies for the treatment of cancer, immune diseases metabolic disorders and infectious diseases as well as the production of cheap drugs  ...  Information gathered from these efforts can be used in synthetic biology-based drug discovery, e.g. translation of signals identified in genome-wide association studies into drug targets.  ... 
doi:10.1159/000341794 pmid:22907209 pmcid:PMC5586729 fatcat:n53kw3i3pjcs5bvygcdgyjtqou

Toward Personalized Medicine in Connectomic Deep Brain Stimulation [article]

Barbara Hollunder, Nanditha Rajamani, Shan H. Siddiqi, Carsten Finke, Andrea A. Kühn, Helen S. Mayberg, Michael D. Fox, Clemens Neudorfer, Andreas Horn
2021 arXiv   pre-print
At the group-level, deep brain stimulation leads to significant therapeutic benefit in a multitude of neurological and neuropsychiatric disorders.  ...  This may be partly explained by limitations of disease-centric strategies that are unable to account for heterogeneous phenotypes and comorbidities observed in clinical practice.  ...  Volker A. Coenen for helpful comments and discussion on an initial draft of this manuscript.  ... 
arXiv:2109.12327v1 fatcat:e7wrsuvhazaehnqxko6foxoyhm

Pharming for Genes in Neurotransmission: Combining Chemical and Genetic Approaches in Caenorhabditis elegans

Stephen M. Blazie, Yishi Jin
2018 ACS Chemical Neuroscience  
Here, we review key approaches to understand neurotransmission and the action of psychiatric drugs in C. elegans.  ...  Chemical and genetic screens are valuable approaches to probe synaptic mechanisms in living animals.  ...  We thank wormbase for information resource, and our laboratory members for discussions.  ... 
doi:10.1021/acschemneuro.7b00509 pmid:29432681 pmcid:PMC6348861 fatcat:qwf3hlvc5vaazjiyhgdahs4j6m

Context-enriched interactome powered by proteomics helps the identification of novel regulators of macrophage activation

Arda Halu, Jian-Guo Wang, Hiroshi Iwata, Alexander Mojcher, Ana Luisa Abib, Sasha A Singh, Masanori Aikawa, Amitabh Sharma
2018 eLife  
The role of pro-inflammatory macrophage activation in cardiovascular disease (CVD) is a complex one amenable to network approaches.  ...  While an indispensible tool for elucidating the molecular underpinnings of complex diseases including CVD, the interactome is limited in its utility as it is not specific to any cell type, experimental  ...  AH thanks Alberto Santos Delgado for fruitful discussions.  ... 
doi:10.7554/elife.37059 pmid:30303482 pmcid:PMC6179386 fatcat:hal5jkc3jjdqjmt6qmi346pfom

A review of dynamical systems approaches for the detection of chaotic attractors in cancer networks

Abicumaran Uthamacumaran
2021 Patterns  
A toolbox of complex systems approaches are discussed for reconstructing the signaling state space of cancer networks, interpreting causal relationships in their time series gene expression patterns, and  ...  Cancers are complex dynamical systems. They remain the leading cause of disease-related pediatric mortality in North America.  ...  Goffredo Arena, and Dr. Mohamed Abdouh of McGill University, and to Dr. Morgan Craig of Universite ´de Montreal, for being my initial conditions.  ... 
doi:10.1016/j.patter.2021.100226 pmid:33982021 pmcid:PMC8085613 fatcat:24cwwzxesfempbtmni4iz4cz5i

Family-based therapies for adolescent alcohol and drug use: research contributions and future research needs

Howard A. Liddle
2004 Addiction  
For instance, improvements in family interaction patterns coincide with decreases in core target alcohol and drug misuse symptoms.  ...  target symptoms of alcohol and drug use, and related problems such as delinquency, school and family problems, and affiliation with substance abusing peers.  ...  Drug Strategies, a Washington, DC-based foundation, worked with exemplary treatment providers and research and treatment experts to identify the most effective empirically supported therapies and outstanding  ... 
doi:10.1111/j.1360-0443.2004.00856.x pmid:15488107 fatcat:hsmi52vpnrf7hffyrwmjrle6ii

Molecular networks in Network Medicine: Development and applications

Edwin K Silverman, Harald H H W Schmidt, Eleni Anastasiadou, Lucia Altucci, Marco Angelini, Lina Badimon, Jean-Luc Balligand, Giuditta Benincasa, Giovambattista Capasso, Federica Conte, Antonella Di Costanzo, Lorenzo Farina (+14 others)
2020 Wiley Interdisciplinary Reviews: Systems Biology and Medicine  
the potential to provide improvements in the diagnosis, prognosis, and treatment of complex diseases.  ...  Important knowledge gaps in Network Medicine include incompleteness of the molecular interactome, challenges in identifying key genes within genetic association regions, and limited applications to human  ...  We thank the other consortium members for their comments and ideas relevant to this manuscript.  ... 
doi:10.1002/wsbm.1489 pmid:32307915 fatcat:ps5v2yzn3ncidcf7avay6f5xli

Climbing Brain Levels of Organisation from Genes to Consciousness

Jean-Pierre Changeux
2017 Trends in Cognitive Sciences  
for drug design.  ...  For instance, microprocessors are claimed to fall short in representing synaptic and neuronal dynamics [1]; in addition, the use of Bayesian statistics (see Glossary) is criticised in the modelling of  ...  The suggested approach tentatively illustrates how these relationships are altered in brain disorders such as ASD and proposes, as a corollary, a new strategy for drug design based on the targeting of  ... 
doi:10.1016/j.tics.2017.01.004 pmid:28161289 fatcat:o2yu6o3sjjdptiruymbmfhhxra

Systems biology beyond networks: Generating order from disorder through self-organization

K. Saetzler, C. Sonnenschein, A.M. Soto
2011 Seminars in Cancer Biology  
their parts are dynamic, contextual and interdependent.  ...  This misperception calls for more tightly coupled mathematical and computational models to biological experiments by creating and designing biological model systems that are accessible to a wide range  ...  This work was funded in part by grants from the National Institutes of Health-National Institute of Environmental Health Sciences (ES08314 and ES018822) and a grant from The Parsemus Foundation.  ... 
doi:10.1016/j.semcancer.2011.04.004 pmid:21569848 pmcid:PMC3148307 fatcat:4qkeazhcnzekfd4gt4fymbfn4q

The Significance of an Enhanced Concept of the Organism for Medicine

Bernd Rosslenbroich
2016 Evidence-Based Complementary and Alternative Medicine  
Here an integrative systems concept is proposed that describes the organism as a multilevel, highly flexible, adaptable, and, in this sense, autonomous basis for a human individual.  ...  Recent developments in evolutionary biology, comparative embryology, and systems biology suggest the necessity of a conceptual shift in the way we think about organisms.  ...  A key idea was that discrete genetic and molecular dysfunction led to specific cancer phenotypes. If these could be identified and then treated with drugs, cancer could be cured.  ... 
doi:10.1155/2016/1587652 pmid:27446221 pmcid:PMC4942667 fatcat:th6gcrnnbrbtxblq3cklvzkyhi

The human proteome – a scientific opportunity for transforming diagnostics, therapeutics, and healthcare

Marc Vidal, Daniel W Chan, Mark Gerstein, Matthias Mann, Gilbert S Omenn, Danilo Tagle, Salvatore Sechi
2012 Clinical Proteomics  
A National Institutes of Health (NIH) workshop was convened in Bethesda, MD on September 26-27, 2011, with representative scientific leaders in the field of proteomics and its applications to clinical  ...  The main purpose of this workshop was to articulate ways in which the biomedical research community can capitalize on recent technology advances and synergize with ongoing efforts to advance the field  ...  Institute of Allergy and Infectious Diseases for their help in organizing the workshop.  ... 
doi:10.1186/1559-0275-9-6 pmid:22583803 pmcid:PMC3388576 fatcat:xkkojbvajfa6xgzotujks4wj74
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