A network-based approach to identify deregulated pathways and drug effects in metabolic syndrome.
Karla Misselbeck,Karla Misselbeck,Silvia Parolo,Francesca Lorenzini,Valeria Savoca,Lorena Leonardelli,Pranami Bora,Melissa J. Morine,Maria Caterina Mione,Enrico Domenici,Enrico Domenici,Corrado Priami,Corrado Priami +12 more
TLDR
A systems biology approach based on network analysis is introduced to investigate deregulated biological processes and subsequently identify drug repurposing candidates and suggest BTK inhibitor ibrutinib to be a promising treatment through its obesity-associated inflammation lowering effect.Abstract:
Metabolic syndrome is a pathological condition characterized by obesity, hyperglycemia, hypertension, elevated levels of triglycerides and low levels of high-density lipoprotein cholesterol that increase cardiovascular disease risk and type 2 diabetes. Although numerous predisposing genetic risk factors have been identified, the biological mechanisms underlying this complex phenotype are not fully elucidated. Here we introduce a systems biology approach based on network analysis to investigate deregulated biological processes and subsequently identify drug repurposing candidates. A proximity score describing the interaction between drugs and pathways is defined by combining topological and functional similarities. The results of this computational framework highlight a prominent role of the immune system in metabolic syndrome and suggest a potential use of the BTK inhibitor ibrutinib as a novel pharmacological treatment. An experimental validation using a high fat diet-induced obesity model in zebrafish larvae shows the effectiveness of ibrutinib in lowering the inflammatory load due to macrophage accumulation. Metabolic syndrome is characterized by complex phenotypes that increases the risk of cardiovascular disease and type 2 diabetes. Here the authors’ integrative network analysis suggests BTK inhibitor ibrutinib to be a promising treatment through its obesity-associated inflammation lowering effect.read more
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Integrative analysis of 111 reference human epigenomes
Anshul Kundaje,Wouter Meuleman,Jason Ernst,Angela Yen,Pouya Kheradpour,Zhizhuo Zhang,Jianrong Wang,Lucas D. Ward,Abhishek Sarkar,Gerald Quon,Matthew L. Eaton,Yi-Chieh Wu,Andreas R. Pfenning,Xinchen Wang,Melina Claussnitzer,Yaping Liu,Mukul S. Bansal,Soheil Feizi-Khankandi,Ah Ram Kim,Richard C Sallari,Nicholas A Sinnott-Armstrong,Laurie A. Boyer,Elizabeta Gjoneska,Li-Huei Tsai,Manolis Kellis +24 more
TL;DR: In this article, the authors describe the integrative analysis of 111 reference human epigenomes generated as part of the NIH Roadmap Epigenomics Consortium, profiled for histone modification patterns, DNA accessibility, DNA methylation and RNA expression.
Tissue-specific regulatory circuits reveal variable modular perturbations across complex diseases
TL;DR: In this article, the authors developed a comprehensive resource of 394 cell type and tissue-specific gene regulatory networks for human, each specifying the genome-wide connectivity among transcription factors, enhancers, promoters and genes.
Journal ArticleDOI
Zebrafish as an animal model for biomedical research
TL;DR: Zebrafish have several advantages compared to other vertebrate models used in modeling human diseases, particularly for large-scale genetic mutant and therapeutic compound screenings, and other biomedical research applications.
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Beneficial effects of flaxseed polysaccharides on metabolic syndrome via gut microbiota in high-fat diet fed mice.
TL;DR: Investigation of the effects of flaxseed polysaccharide on lipid metabolism and gut microbiota in high-fat-diet-fed mice suggests that FSP may use as a prebiotic for preventing MetS by modulating the gut microbiota.
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Transgenic fluorescent zebrafish lines that have revolutionized biomedical research.
Chong Pyo Choe,Seok-Yong Choi,Yun Kee,Min Jung Kim,Seok-Hyung Kim,Yoonsung Lee,Hae Chul Park,Hyunju Ro +7 more
TL;DR: In this article, the authors summarize representative transgenic fluorescent zebrafish lines that have revolutionized biomedical research on signal transduction, the craniofacial skeletal system, the hematopoietic system, nervous system, urogenital system, digestive system and intracellular organelles.
References
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Tissue-based map of the human proteome
Mathias Uhlén,Mathias Uhlén,Linn Fagerberg,Björn M. Hallström,Cecilia Lindskog,Per Oksvold,Adil Mardinoglu,Åsa Sivertsson,Caroline Kampf,Evelina Sjöstedt,Evelina Sjöstedt,Anna Asplund,IngMarie Olsson,Karolina Edlund,Emma Lundberg,Sanjay Navani,Cristina Al-Khalili Szigyarto,Jacob Odeberg,Dijana Djureinovic,Jenny Ottosson Takanen,Sophia Hober,Tove Alm,Per-Henrik Edqvist,Holger Berling,Hanna Tegel,Jan Mulder,Johan Rockberg,Peter Nilsson,Jochen M. Schwenk,Marica Hamsten,Kalle von Feilitzen,Mattias Forsberg,Lukas Persson,Fredric Johansson,Martin Zwahlen,Gunnar von Heijne,Jens Nielsen,Jens Nielsen,Fredrik Pontén +38 more
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