Systems Biology Approaches in Autophagy Research.

As a classical form of programmed cell death, autophagy is widely involved in cellular metabolism and vital for the maintenance of homeostasis in physiological and pathological states. With multiple levels of regulation and signaling integrated in, autography presents complicated relevance with various diseases, such as cancer and neurological diseases. The emerging subject, systems biology, along with multi-omics approaches, offers a new strategy to investigate these interactive processes from a holistic perspective. In this chapter, we focus on the systems biology method for autophagy research and introduce essential research skills and procedures. The critical step of systematic study is to explore interplay between biological molecules based on massive biological data, which requires construction of networks in different biological levels, modification, and identification of key pathways and targets via optimized algorithm and experimental verification. Guided by systems biology research, drug design can thus be strengthened by efficient screening and accurate evaluation. Overall, systems biology promises to act as a powerful tool which both helps to clarify the profound mechanism and to develop efficacious medicine.

[1]  H. Rhim,et al.  Therapeutic implication of autophagy in neurodegenerative diseases , 2017, BMB reports.

[2]  Giovanni Paternostro,et al.  Cardiac Systems Biology , 2005, Annals of the New York Academy of Sciences.

[3]  K. Obermayer,et al.  Systems Neurobiology of the Dysfunctional Brain: Schizophrenia , 2007 .

[4]  P. Colas,et al.  Yeast two-hybrid methods and their applications in drug discovery. , 2012, Trends in pharmacological sciences.

[5]  Tony Pawson,et al.  The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells , 2014, Nature Methods.

[6]  E. White,et al.  The Double-Edged Sword of Autophagy Modulation in Cancer , 2009, Clinical Cancer Research.

[7]  S. Eddy.  Hidden Markov models. , 1996, Current opinion in structural biology.

[8]  A. Lusis,et al.  Considerations for the design of omics studies , 2017 .

[9]  Z. Yue,et al.  Autophagy in neurodegenerative diseases , 2016, Brain Research.

[10]  Aylwin Ng.  Integrative systems biology and networks in autophagy , 2010, Seminars in Immunopathology.

[11]  E. Kunkel.  Systems biology in drug discovery , 2004, Nature Biotechnology.

[12]  T. Hankemeier,et al.  Metabolomics-based systems biology and personalized medicine: moving towards n = 1 clinical trials? , 2006, Pharmacogenomics.

[13]  Paul A Clemons,et al.  The Connectivity Map: Using Gene-Expression Signatures to Connect Small Molecules, Genes, and Disease , 2006, Science.

[14]  S. Dooley,et al.  Primary mouse hepatocytes for systems biology approaches: a standardized in vitro system for modelling of signal transduction pathways. , 2006, Systems biology.

[15]  Jason Weston,et al.  A user's guide to support vector machines. , 2010, Methods in molecular biology.

[16]  N. Mizushima,et al.  Autophagy: process and function. , 2007, Genes & development.

[17]  Daniel J. Klionsky,et al.  Autophagy fights disease through cellular self-digestion , 2008, Nature.

[18]  F. Bruggeman,et al.  The nature of systems biology. , 2007, Trends in microbiology.

[19]  Joseph A. Hill,et al.  Tuning flux: autophagy as a target of heart disease therapy , 2011, Current opinion in cardiology.

[20]  Lee A. D. Cooper,et al.  The OncoPPi network of cancer-focused protein–protein interactions to inform biological insights and therapeutic strategies , 2017, Nature Communications.

[21]  B. Hall.  Evolutionary Developmental Biology , 1999, Springer Netherlands.

[22]  G. D. Gatta,et al.  Systems and Synthetic biology: tackling genetic networks and complex diseases , 2009, Heredity.

[23]  Kevin Bray,et al.  Autophagy promotes tumor cell survival and restricts necrosis, inflammation, and tumorigenesis. , 2006, Cancer cell.

[24]  Andreas Krämer,et al.  Causal analysis approaches in Ingenuity Pathway Analysis , 2013, Bioinform..

[25]  Guido Kroemer,et al.  Autophagy in the Pathogenesis of Disease , 2008, Cell.

[26]  L. Hood,et al.  Systems medicine: the future of medical genomics and healthcare , 2009, Genome Medicine.

[27]  Younho Choi,et al.  Autophagy during viral infection — a double-edged sword , 2018, Nature Reviews Microbiology.

[28]  A. Raftery.  Bayesian Model Selection in Social Research , 1995 .

[29]  A. Cuervo,et al.  Autophagy and disease: always two sides to a problem , 2012, The Journal of pathology.

[30]  Margaret A. Johns,et al.  Corrigendum: The OncoPPi network of cancer-focused protein–protein interactions to inform biological insights and therapeutic strategies , 2017, Nature Communications.

[31]  H. Kitano.  Systems Biology: A Brief Overview , 2002, Science.

[32]  Anthony C. Bishop,et al.  Rapid structure-activity and selectivity analysis of kinase inhibitors by BioMAP analysis in complex human primary cell-based models. , 2004, Assay and drug development technologies.

[33]  Anne-Claude Gingras,et al.  Affinity-purification mass spectrometry (AP-MS) of serine/threonine phosphatases. , 2007, Methods.

[34]  A. Lyakhovich,et al.  The interplay between autophagy and tumorigenesis: exploiting autophagy as a means of anticancer therapy , 2018, Biological reviews of the Cambridge Philosophical Society.

[35]  J. Rullmann,et al.  Systems biology for battling rheumatoid arthritis: application of the Entelos PhysioLab platform. , 2005, Systems biology.

[36]  Pamela K. Kreeger,et al.  Cancer systems biology: a network modeling perspective , 2009, Carcinogenesis.