Welcome to the website of the LINK-Group!

An updated version of the user friendly, Cytoscape plug-in of the ModuLand modularization program became available

May 2012

An updated version of the user-friendly, platform independent implementation of the LinkLand method of the ModuLand method family published earlier in PLoS ONE became available as a plug-in for the widely used Cytoscape program. The paper introducing the plug-in can be accessed as a pre-print in arxiv.org. The introducing paper demonstrates the usefulness of the method

1. to identify an extensively overlapping modular structure;
2. to define a modular core and hierarchy allowing an easier functional annotation;
3. to identify key nodes of high community centrality, modular overlap or bridgeness in protein structure, protein-protein interaction and metabolic networks.

The program file and its User Guide can be downloaded from here.

A joint paper with Ruth Nussinov on the new drug-design paradigm of allo-network drugs was published as the cover story of the December issue of Trends in Pharmacological Sciences

November 2011

The paper proposed that the concept of allosteric drugs can be broadened to allo-network drugs, whose effects can propagate either within a protein, or across several proteins, to enhance or inhibit specific interactions along a pathway. Allo-network drugs can achieve specific, limited changes at the systems level, and in this way can achieve fewer side effects and lower toxicity. The paper summarized possible methods to identify allo-network drug targets and sites. The concept outlined a new paradigm in systems-based drug design. The paper, which was published as the cover story of the December issue of Trends in Pharmacological Sciences, can be downloaded from here.

Ágoston Mihalik's paper showing a partial desintegration of the yeast interactome as a general model of systems level adatptation processes has been published in PLoS Computational Biology

July 2011

The paper described that heat shock induces a marked decrease in the overlap of the communities (modules) of the yeast interactome. Our results indicated that heat shock induces a partial disintegration of the protein-protein interaction network. The residual inter-modular bridges, maintaining the integrity of the interactome after stress, were key proteins of stress-survival. The changes observed may be rather general occurring at the initial phase of crises in many complex systems, such as proteins in physical stretch, ecosystems in abrupt environmental changes or social networks in economic crisis. De-coupling and re-wiring of modules emerges as a general model of adaptation and learning. The paper and its Supplement, which were published in PLoS Computational Biology, can be downloaded from here.

Peter Csermely became a network and systems biology editor of (Nature) Scientific Reports

Peter Csermely became an editor of (Nature) Scientific Reports. The newly started journal publishes articles of all fields.

The Hungarian version of the book Weak Links was voted to the best 500 Hungarian books

June 2011

A wide panel of experts has recently determined the “Márai-list”, which is a list of the top 500 Hungarian books (including the top 250 non-fiction books) among a competing 8,000 books recommended to all Hungarian libraries. The Hungarian version of the book Weak Links (a 2009 Springer book on networks, which is downloadable from here or at Google) has been included to this selection of the top 250 non-fiction Hungarian books.

A summary paper of our results appeared in Science Signaling: Network-based tools in the identification of novel drug-targets

May 2011

A summary paper and an accompanying slide show of our work appeared in the May 2011 issue of Science Signaling. Slides were updated from the opening presentation at the International Conference on Systems Biology of Human Disease (SBHD) in Boston, Massachusetts, 16 to 18 June 2010. The paper contains several novel ideas on network dynamics and drug design, a summary of our very recent results as well as a brief description of a few ongoing projects. The paper is available here and the accompanying slideshow is downloadable from here.

Turbine, an extensive tool for the analysis of network perturbations and dynamics

May 2011

Turbine is an open-source network analysis package for simulating network dynamics. It is particularly suited for experiments involving perturbations (i.e.: observing the effects of outside stimulations on a target network). Turbine is written in C++, and is currently available for Windows and Linux systems. Turbine is able to accommodate any model or real world networks, single, multiple, or continuous perturbations with custom-made delay or dissipation dynamics. You may see a more detailed characterization of the program and download all its components, source code, and detailed instructions here.

NetworGame, a progam package to simulate spatial games on model and real world networks with individual starting strategies of any nodes

May 2011

The NetworGame program package is a cross-platform, multi-threaded, generic tool to simulate repeated spatial games. NetworGame accommodates any model or real-world networks and is able to set individual starting strategies to any nodes. The NetworGame program package is a console application augmented with a Graphical User Interface, and a data mining tool, which helps extracting and storing data in comma-separated value (csv) format. You may see a more detailed characterization of the program and download its Linux- or Windows-compatible packages, and detailed instructions here.

Peter Csermely became the network and systems biology editor of Cell Stress and Chaperones

May 2011

Peter Csermely became the Molecular Chaperones, Networks, and Systems Biology Section Editor of Cell stress and Chaperones (5-year IF: 3,2). The journal publishes articles related to cellular stress and molecular chaperones for 16 years.

The concept of signalogs has been published in PLoS ONE

April 2011

In connection with the SignaLink database, we published the concept of signaling orthologs, called signalogs in PLoS ONE. The paper (which also contains and experimental "proof-of-concept" on the predicting power of SignaLink) can be downloaded from here. SignaLink is a manually curated signalling network, which contains 1554 protein components and 1461 interactions of eight major signalling pathways from the nematode Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and humans. Unlike worms and flies, all the eight human signalling pathways have the potential to cross-talk with all other pathways. The utilisation of these cross-talks is tissue-specific. We predicted 271 novel signalling proteins in the three species from which all of the six novel C. elegans Notch components were verified experimentally. 40 novel drug target candidates were identified. Posters on the project were awarded both at the March (Tamás Korcsmáros) and September (Illés Farkas) FEBS signaling conferences. Manuscript, supporting website: http://signalink.org.

A hypothesis on protein signal transduction mechanism and a comprehensive review on disordered proteins

February 2011

A LINK-Group paper has been accepted in the special issue of Current Protein and Peptide Science on disordered proteins (edited by Vladimir Uversky). The paper gives a comprehensive review on A.) the network descriptions of disordered proteins, B.) the consequences of network disorder on protein structure and dynamics; and C.) the functional consequences of protein disorder in cellular networks. Besides these the paper formulates two hypotheses: I.) on a novel classification of proteins to stratus- and cumulus-type classes describing the two ways of intramolecular signal transduction in these networks, and II.) suggesting that disorder plays a major role to reach hidden, rarely visited protein conformations important e.g. in cellular signaling. The paper can be downloaded from here.

The ModuLand method has been featured in Science Signaling

February 2011

The February 2011 issue of Science Signaling highlighted the ModuLand method as one of the two network modeling tools of its ST Netwatch section. The method has been published earlier in PLoS ONE and we currently develop its user-friendly application as well as its sequel(s). The free computer program package with User Guide, algorithms and background can be downloaded from here.

Peter Csermely became an Editor of PLoS ONE

November 2010

Peter Csermely became one of the Editors of PLoS ONE. The journal has reached an impact factor of 4.4 and became one of the largest scientific journals of the world. The LINK-Group had two key publications already in this journal, one about spatial games and another about the novel modularization concept of communitiy landscapes.

Our paper on an extended concept of induced-fit and conformational selection was published as the cover story of the October issue of the Trends in Biochemical Sciences

October 2010

In collaboration with Ruth Nussinov we described an extended conformational selection model, which embraces a repertoire of selection and adjustment processes. Induced fit can be viewed as a subset of this repertoire, whose contribution is affected by the bond-types stabilizing the interaction and the differences between the interacting partners. We argue that protein segments whose dynamics are distinct from the rest of the protein (‘discrete breathers’) can govern conformational transitions and allosteric propagation that accompany binding processes, and as such may be more sensitive to mutational events. Additionally, we highlight the dynamic complexity of binding scenarios as they relate to events such as aggregation and signalling, and the crowded cellular environment. The paper can be downloaded from here.

The ModuLand overlapping modularization method family has been published in PLoS ONE

August 2010

Our paper introducing the novel concept of ModuLand has been accepted in PLoS ONE. Moduland is an integrative method family determining overlapping network modules as hills of an influence function-based, centrality-type community landscape, and including several widely used modularization methods as special cases. As various adaptations of the method family, we developed several algorithms, which provide an efficient analysis of weighted and directed networks, and (1) determine pervasively overlapping modules with high resolution; (2) uncover a detailed hierarchical network structure allowing an efficient, zoom-in analysis of large networks; (3) allow the determination of key network nodes and (4) help to predict network dynamics. Published version: http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0012528; Supporting website with all downloadable algorithms: http://www.linkgroup.hu/modules.php

Peter Csermely published a Nature Journal Club paper, and its background info in Trends in Biochem. Sci. on creative elements

July 2008

LINK-Group member, Péter Csermely published a Nature Journal Club paper on the active centers of enzymes and proposed that the protein structure network elements forming these active centers, called creative elements, can be found in all evolved networks and play a key role in the development, inheritance and regulation of evolvability. The detailed description of creative elements appeared as a cover story in Trends in Biochem. Sci. and can be found here.Download it!