Dynamical pathway analysis

Xiong, Hao; Choe, Yoonsuck

doi:10.1186/1752-0509-2-9

Cited by 10 publications

(5 citation statements)

References 33 publications

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“…Despite of the clear applicability of network controllability to drug design (i.e. finding the nodes, which can shift molecular networks of the cell from a malignant state to a healthy state) there were only a few studies testing various aspects of this rich methodology in drug design (Xiong & Choe, 2008; Luni et al, 2010). Development of drug-related applications of network influence and control models is an important task of future studies.…”

Section: An Inventory Of Network Analysis Tools Helping Drug Designmentioning

confidence: 99%

“…(Xiong & Choe, 2008; Antal et al, 2009; Kitsak et al, 2010; Luni et al, 2010; Farkas et al, 2011; Liu et al, 2011; Liu et al, 2012; Mones et al, 2012; Banerjee & Roy, 2012 ; Cowan et al, 2012; Nepusz & Vicsek, 2012; Valente, 2012; Wang et al, 2012a). Influential nodes may have a hidden influence, like those highly unpredictable, ‘creative’ nodes, which may delay critical transitions of diseased cells (see Sections 2.2.2. and 2.5.2. for more details; Csermely, 2008; Scheffer et al, 2009, Farkas et al, 2011; Sornette & Osorio, 2011; Dai et al, 2012).…”

Section: Areas Of Drug Design: An Assessment Of Network-related Admentioning

confidence: 99%

“…Potential methods to find influential nodes redirecting perturbations, affecting cellular cooperation or asserting network control have been described in Sections 2.3.4, 2.5.2 and 2.5.3 (Xiong & Choe, 2008;Antal et al, 2009;Kitsak et al, 2010;Luni et al, Liu et al, , 2012Banerjee & Roy, 2012;Cowan et al, 2012;Mones et al, 2012;Nepusz & Vicsek, 2012;Valente, 2012;Wang et al, 2012a). Influential nodes may have a hidden influence, like those highly unpredictable, 'creative' nodes, which may delay critical transitions of diseased cells (see Sections 2.2.2 and 2.5.2 for more details; Csermely, 2008;Scheffer et al, 2009;Farkas et al, 2011;Sornette & Osorio, 2011;Dai et al, 2012).…”

Section: Two Strategies Of Network-based Drug Targeting: the Central ...mentioning

confidence: 99%

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Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Csermely

Korcsmáros

Kiss

et al. 2013

Pharmacology & Therapeutics

820

661

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Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The “central hit strategy” selectively targets central node/edges of the flexible networks of infectious agents or cancer cells to kill them. The “network influence strategy” works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach.

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Section: An Inventory Of Network Analysis Tools Helping Drug Designmentioning

confidence: 99%

Section: Areas Of Drug Design: An Assessment Of Network-related Admentioning

confidence: 99%

Section: Two Strategies Of Network-based Drug Targeting: the Central ...mentioning

confidence: 99%

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Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Csermely

Korcsmáros

Kiss

et al. 2013

Pharmacology & Therapeutics

820

661

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“…We think that the impact of changes in the forest ecosystem can be measured indirectly through the effects on community phenology by analysing the dynamics of recovery in a multiscale fashion, from genetic variation via tree regeneration characteristics (e.g., regeneration composition vs. canopy composition) to multipopulation structure via disturbance characteristics (e.g., disturbance regimes vs. management treatments). To enhance the adaptive potential and associated ecosystem services of forests, we propose the development of landscape-genetic monitoring of the differential dynamic properties of ecosystems [20,141].…”

Section: Ways Of Forest Self-regulation Natural Regeneration and Repr...mentioning

confidence: 99%

Concept for Genetic Monitoring of Hemiboreal Tree Dynamics in Lithuania

Petrokas

Kavaliauskas

2022

Land

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In this review, we focus on the importance of the dynamics of hemiboreal trees in the existing forest landscape and habitats for the genetic monitoring of community phenology, in order to obtain characteristic plant cycles as well as their responses to seasonal and climatic changes. The goal of our review is to: (i) determine the regenerative behaviour of hemiboreal tree species, (ii) propose a concept for the genetic monitoring of tree dynamics in the main forest habitat types of Lithuania’s forest landscape based on field observations, e.g., community phenology, and (iii) discuss ways of forest self-regulation, natural regeneration, and reproduction. We have chosen Lithuania as a case study for this review because it is a Northern European country that falls completely within the hemiboreal forest zone, which is often overlooked in terms of climate change effects. Our review highlights the importance of understanding the genetic responses of individual tree species and how they interact in the forest community after disturbance, as well as the need to sustainably monitor them at habitat and landscape scales. To enhance the adaptive potential and associated ecosystem services of forests, we propose the development of landscape-genetic monitoring of the differential dynamic properties of ecosystems.

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“…It is cautioned that, although connections can be made between these MIPs and the synergistic potency-enhancing modes, many of these interconnections are much more complicated than those analyzed here. Their activities are highly dynamic [27], [28], [29] influenced by genetic variations [30], environmental factors [31], host’s behavior [32], and therapeutic scheduling [33]. Their use should be more appropriately viewed as a start to a more comprehensive analysis of the potency-enhancing modes in NP combinations.…”

Section: Introductionmentioning

confidence: 99%

What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

et al. 2012

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There have been renewed interests in natural products as drug discovery sources. In particular, natural product combinations have been extensively studied, clinically tested, and widely used in traditional, folk and alternative medicines. But opinions about their therapeutic efficacies vary from placebo to synergistic effects. The important questions are whether synergistic effects can sufficiently elevate therapeutic potencies to drug levels, and by what mechanisms and at what odds such combinations can be assembled. We studied these questions by analyzing literature-reported cell-based potencies of 190 approved anticancer and antimicrobial drugs, 1378 anticancer and antimicrobial natural products, 99 natural product extracts, 124 synergistic natural product combinations, and 122 molecular interaction profiles of the 19 natural product combinations with collective potency enhanced to drug level or by >10-fold. Most of the evaluated natural products and combinations are sub-potent to drugs. Sub-potent natural products can be assembled into combinations of drug level potency at low probabilities by distinguished multi-target modes modulating primary targets, their regulators and effectors, and intracellular bioavailability of the active natural products.

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Dynamical pathway analysis

Cited by 10 publications

References 33 publications

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Structure and dynamics of molecular networks: A novel paradigm of drug discovery

Concept for Genetic Monitoring of Hemiboreal Tree Dynamics in Lithuania

What Does It Take to Synergistically Combine Sub-Potent Natural Products into Drug-Level Potent Combinations?

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