Advanced Systems Biology Methods in Drug Discovery and Translational Biomedicine

Abstract

Systems biology is in an exponential development stage in recent years and has been widely utilized in biomedicine to better understand the molecular basis of human disease and the mechanism of drug action. Here, we discuss the fundamental concept of systems biology and its two computational methods that have been commonly used, that is, network analysis and dynamical modeling. The applications of systems biology in elucidating human disease are highlighted, consisting of human disease networks, treatment response prediction, investigation of disease mechanisms, and disease-associated gene prediction. In addition, important advances in drug discovery, to which systems biology makes significant contributions, are discussed, including drug-target networks, prediction of drug-target interactions, investigation of drug adverse effects, drug repositioning, and drug combination prediction. The systems biology methods and applications covered in this review provide a framework for addressing disease mechanism and approaching drug discovery, which will facilitate the translation of research findings into clinical benefits such as novel biomarkers and promising therapies.

If Systems Approach is the Way Forward, What can the Ayurvedic Theory of <i>Tridosha</i> Teach Us?

“…Clinical medicine has entered an era of systemic approach [1][2][3][4][5] . In this context, ayurveda has much to offer.…”

“…twenty factors (Vimśati guna) 15 : (1,2) heavy (guru) and light (laghu); (3,4) cold (sheeta) and hot (ushna); (5,6) oiliness (snigdha), dryness (ruksha); (7,8) slow/dull (manda), sharp (tikshna); (9,10) immobility (sthira), mobility (sara); (11,12) soft (mrudu), hard (kathina); (13,14) adhesive/sticky (pichchila), non-slimy/non-adhesive (vishada); (15,16) smooth (shlakshna), rough (khara); (17,18) minuteness (sukshma), gross (sthula); (19,20) viscidity (sandra), diffusivity/fluidity (drava). These properties at the opposite ends of a continuum are inherent to material bodies and used in ayurveda to understand the human system.…”

“…Data from the 'omics' technologies is redefining the understanding of cell as a system rather than as sum of its components. This has not only revolutionized the emerging field of systems biology but has also fuelled growing interest in applying systems theory to clinical medicine [2][3][4][5] . As these advances continue to broaden our understanding of human complexity and provide methodologies for patient-centric systems approach, it is pertinent to have a relook at the Indian medical system of ayurveda known to have an integrated approach to health and disease.…”

Copy Number Networks to Guide Combinatorial Therapy of Cancer and Proliferative Disorders

“…Regardless of modality, it is increasingly difficult to gain approval for new drugs, leading to blocked therapeutic pipelines (Csermely et al, 2013;Gupta et al, 2013;Pujol et al, 2010;Zou et al, 2013). New drugs can fail at multiple steps in the testing process, often because of unexpected safety or toxicological concerns.…”

“…In addition to identifying new drug targets, networks can be used to redeploy drugs from other disorders (Gupta et al, 2013;Zou et al, 2013). This approach is called drug repositioning or repurposing.…”