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iBIG:An Integrative Network Tool for Supporting Human disease mechanism Studies

Genomics, Proteomics & Bioinformatics 2013年第3期11卷 166-171页

作者： Jiya Sun Yuyun Pan Xuemei Feng Huijuan Zhang Yong Duan Hongxing Lei CAS Key Laboratory of Genome Sciences and Information Beijing Institute of GenomicsChinese Academy of Sciences Graduate University of Chinese Academy of Sciences UC Davis Genome Center and Department of Biomedical Engineering

Understanding the mechanism of complex human diseases is a major scientitic challenge. Towards this end, we developed a web-based network tool named iBIG （stands for integrative BioloGy）, which incorporates a variety of information on gene interaction and regulation. The generated network can be annotated with various types of information and visualized directly online. In addition to the gene networks based on physical and pathway interactions, networks at a functional level can also be constructed. Furthermore, a supplementary R package is provided to process microarray data and generate a list of important genes to be used as input for iBIG. To demonstrate its usefulness, we collected 54 microarrays on common human diseases including cancer, neurolog- ical disorders, infectious diseases and other common diseases. We processed the microarray data with our R package and constructed a network of functional modules perturbed in common human diseases. Networks at the functional level in combination with gene networks may provide new insight into the mechanism of human diseases, iBIG is freely available at http：//***/ibig.

关键词： Network Functional module disease mechanism Microarray Web server

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Computational and theoretical modeling of intermediate filament networks:Structure,mechanics and disease

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Acta Mechanica Sinica 2012年第4期28卷 941-950页

作者： Zhao Qin Markus J. Buehler Laboratory for Atomistic and Molecular Mechanics (LAMM) Department of Civil and Environmental Engineering 77 Massachusetts Ave. Massachusetts Institute of Technology Room 1-235 A&B Cambridge 02139 MA USA Center for Computational Engineering Massachusetts Institute of Technology 77 Massachusetts Ave. Cambridge MA 02139 USA Center for Materials Science and Engineering Massachusetts Institute of Technology77 Massachusetts Ave. Cambridge MA 02139 USA

Intermediate filaments, in addition to microtubules and actin microfilaments, are one of the three major components of the cytoskeleton in eukaryotic cells. It was discovered during the recent decades that in most cells, intermediate filament proteins play key roles to reinforce cells subjected to large-deformation, and that they participate in signal transduction, and it was proposed that their nanome- chanical properties are critical to perform those functions. However, it is still poorly understood how the nanoscopic structure, as well as the combination of chemical composition, molecular structure and interfacial properties of these protein molecules contribute to the biomechanical properties of filaments and filament networks. Here we review recent progress in computational and theoretical studies of the intermediate filaments network at various levels in the protein＇s structure. A multiple scale method is discussed, used to couple molecular modeling with atomistic detail to larger-scale material properties of the networked material. It is shown that a finer-trains-coarser method- ology as discussed here provides a useful tool in understanding the biomechanical property and disease mechanism of intermediate filaments, coupling experiment and simulation. It further allows us to improve the understanding of associated disease mechanisms and lays the foundation for engineering the mechanical properties of biomaterials.

关键词： Intermediate filament network - Multiple scale method Nanoscopic structure Mechanics disease mechanism Molecular mechanics

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Attractor landscape analysis of the cardiac signaling network reveals mechanism-based therapeutic strategies for heart failure

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Journal of Molecular Cell Biology 2018年第3期10卷 180-194页

作者： Daebeom Park Ho-Sung Lee Jun Hyuk Kang Seon-Myeong Kim Jeong-Ryeol Gong Kwang-Hyun Cho Laboratory for Systems Biology and Bio-inspired Engineering Department of Bio and Brain Engineering Korea Advanced Institute of Science and Technology (KAIST) Daejeon 34141 Republic of Korea Graduate School of Medical Science and Engineering KAIST Daejeon 34141 Republic of Korea

Apoptosis and hypertrophy of cardiomyocytes are the primary causes of heart failure （HF）, a global leading cause of death, and are regulated through the complicated intracellular signaling network, limiting the development of effective treatments due to its complexity. To identify effective therapeutic strategies for HF at a system level, we develop a large-scale comprehensive mathematical model of the cardiac signaling network by integrating all available experimental evidence. Attractor landscape analysis of the network model identifies distinct sets of control nodes that effectively suppress apoptosis and hypertrophy of cardiomyocytes under ischemic or pressure overload-induced HF, the two major types of HF. Intriguingly, our system-level analysis suggests that intervention of these control nodes may increase the efficacy of clinical drugs for HF and, of most importance, different combinations of control nodes are suggested as potentially effective candidate drug targets depending on the types of HF. Our study provides a systematic way of developing mechanism-based therapeutic strategies for HF.

关键词： heart failure mathematical modeling cardiac signaling network systems analysis disease mechanism mechanism-based therapeutic strategy systems biology

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Why do we study animal toxins?

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Zoological Research 2015年第4期36卷 183-221页

作者： Yun ZHANG Key Laboratory of Animal Models and Human disease mechanisms of The Chinese Academy of Sciences & Yunnan Province Kunming Institute of Zoology Chinese Academy of Sciences

Venom （toxins） is an important trait evolved along the evolutionary tree of animals. Our knowledges on venoms, such as their origins and loss, the biological relevance and the coevolutionary patterns with other organisms are greatly helpful in understanding many fundamental biological questions, i.e., the environmental adaptation and survival competition, the evolution shaped development and balance of venoms, and the sophisticated correlations among venom, immunity, body power, intelligence, their genetic basis, inherent association, as well as the cost-benefit and trade-offs of biological economy. Lethal animal envenomation can be found worldwide However, from foe to friend, toxin studies have led lots of important discoveries and exciting avenues in deciphering and fighting human diseases, including the works awarded the Nobel Prize and lots of key clinic therapeutics. According to our survey, so far, only less than 0.1% of the toxins of the venomous animals in China have been explored. We emphasize on the similarities shared by venom and immune systems, as well as the studies of toxin knowledge-based physiological toxin-like proteins/peptides （TLPs）. We propose the natural pairing hypothesis. Evolution links toxins with humans. Our mission is to find out the right natural pairings and interactions of our body elements with toxins, and with endogenous toxin-like molecules. Although, in nature, toxins may endanger human lives, but from a philosophical point of view, knowing them well is an effective way to better understand ourselves. So, this is why we study toxins.

关键词： Toxins Survival competition Evolution disease mechanism Drug development

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