Thursday, September 17, 2015

Bridging traditional and modern medicine with a data and informatics driven drug discovery framework

How could we possibly bridge elements from traditional medicinal knowledge and modern medicine with the help of computational tools to accelerate the drug discovery process?

Here I discuss an integrative strategy that is based on on our work conducted at CSIR-Institute of Himalayan Bioresource Technology (Palampur) and Indian Institute of Technology Jodhpur.

Diseases are manifestations of irregularities in cellular and molecular mechanisms. A large number of diseases have been scrutinized at the level of pathways and molecular causative agents, in addition to understanding contributing environmental factors. However, contrary to expectations, reductionist investigations of complex diseases have led to increase in noise making it difficult to ascertain specific causative molecular mechanisms that could be used to control the disease. Hence prompted by increasing need of integrating disparate molecular elements, systems biological strategies have been developed to create a holistic picture of molecular mechanisms underlying complex diseases. We have implemented network models, graph theoretical representations of interconnected systems, for the analysis of disease interactomes (Vashisht and Bagler, 2012; Randhawa and Bagler, 2012; Randhawa et al., 2013). These integrative models allow one to wade through the noise and to pin down specific targets and regulatory mechanisms, thus providing a rational strategy towards disease control. This approach has paved way for ‘network medicine’ towards deciphering causal relationship of diseases, molecular agents and regulatory mechanisms.

Historically, through trial and error, plant extracts have been identified as effective means of mitigating diseases without necessarily understanding their mode of action. Plants contain vast array of natural compounds with important pharmacological properties and their extracts have been used for treating various diseases from ancient times. Traditional medicinal systems are rich source of such information which is often complemented by modern medicinal studies. How could we possibly bridge traditional knowledge and modern medicine to facilitate accelerated drug discovery? Informed with our research explorations (Pathania et al., 2013;Pathania, Ramakrishnan, Randhawa, et al.,2015; Pathania, Ramakrishnan, and Bagler, 2015; Jain et al., 2015a; Perumal et al.,2015; Randhawa and Bagler, 2012; Randhawa etal., 2013; Vashisht and Bagler, 2012; Jain et al., 2015b; Jain and Bagler, 2015), we propose a data and informatics driven framework that juxtaposes systems biological models of complex diseases, reported efficacy of medicinal plant extracts, and compilations of structured libraries of small molecules, aimed at an effective and rational drug discovery process.

The proposed data and informatics driven integrative framework bridges traditional and modern medicine by bringing together various jigsaw pieces of knowledge as well as data enabled hypothesis driven search for therapeutic molecules. Following illustration depicts the framework and our contribution towards its various facets.


(An extended version of this article is to be published in the Advanced Techniques in Biology and Medicine journal)

References:
(2)   Randhawa,V. and Bagler,G. (2012) Identification of SRC as a Potent Drug Target for Asthma, Using anIntegrative Approach of Protein Interactome Analysis and In Silico DrugDiscovery. OMICS A Journal of Integrative Biology, 16(10), 512–526.
(3)   Randhawa,V., Sharma,P, Bhushan,S and Bagler,G (2013) Identification of key nodes of Type 2 Diabetes Mellitus protein interactome andstudy of their interactions with phloridzinOMICS A Journal of Integrative Biology, 17(6), 302–317.
(5)   Pathania,S., Ramakrishnan,S.M., Randhawa,V. and Bagler,G (2015) SerpentinaDB: a database of plant-derived moleculesof Rauvolfia serpentina. BMC Complementary and Alternative Medicine, 15, 262.
(6)   Pathania,S., Ramakrishnan,S.M., and Bagler,G. (2015) Phytochemica: a platform to explore phytochemicals ofmedicinal plants. Database (Oxford University Press), 2015, 1–8.
(7)   Jain,A, Rakhi,NK and Bagler,G (2015a) Spices form the basis of food pairing in Indian cuisine. arXiv:1502.03815.
(8)   Jain,A, Rakhi,NK and Bagler,G (2015b) Analysis of food pairing in regional cuisines of India. arXiv:1505.00890 (accepted, PLoS ONE).
(9)   Jain,A. and Bagler,G. (2015) Culinary evolution models for Indian cuisines. arXiv:1505.00155.
(10)  Perumal,S, Dubey,K, Badhwar,R, Kodimattan,JG, Sharma RK, Bagler,G, Madhan,B and Kar,K (2015) Capsaicin inhibits collagen fibril formation and increases the stability ofcollagen fibers. European Biophysical Journal, 44, 69–76.

Wednesday, September 9, 2015

Discovery of the molecular essence of Indian cuisine and opportunities for India

Are there fundamental principles underlying the composition of traditional recipes? Recipes have evolved for decades, if not for centuries, by the process of tinkering to emerge as survivors. They are shaped by complex interplay of culture, climate, geography and genetics. To expect to have an underlying pattern or rules by which they are designed is perhaps too much to ask for. One such principle that was suggested to be at the core of recipes is that of ‘food pairing’. Chef Heston Blumenthal proposed that a recipe tastes better when its ingredients are similar in flavor. This notion has been prevalent in the culinary industry across the world. While one doesn’t understand why humans would be wired to have olfactory (smell) and gustatory (taste) sensory mechanisms to appreciate one kind of pairing over the other, the concept of ‘positive food pairing’ has been in vogue among chefs, culinary enthusiasts and food scientists.


With the discovery of ‘contrasting food pairing’, hitherto unreported in the culinary world, with our research conducted at IIT Jodhpur, we showed that Indian cuisine is distinct and stands unique in its characteristic contrasting food pairing phenomenon (“Spices form the basis of food pairing in Indiancuisine”, A Jain, NK Rakhi and G Bagler, arXiv:1502:03815). This discovery has taken the culinary world by storm, and has been identified as an emerging technology by the prestigious MIT Technology Review.

Discovery of laws and principles propel technological innovations and commercial applications amply demonstrated in the past in the domains of physics, chemistry and biology. While invariant laws in culinary practices are a far cry from those in hard sciences, the knowledge of principles ingrained in their composition provides impetus for their scientific development and commercial utility. Understanding the molecular make up of recipe also reveals the inner instincts of its consumers and has the potential to transform food, catering and tourism industry. With the insights gained in the process of discovery of molecular essence of Indian cuisine, I present following four areas of opportunity that are made available to India.



Novel recipes
The space of possible recipes is astronomically large (~10174) given typical size of a recipe (8) and number of ingredients available (193). It is practically impossible to create all those recipes and identify the ones that are palatable. With the knowledge of ‘complementary food pairing’ principle in Indian cuisine, one could implement data- and computation-driven algorithmic strategies to mine for recipes with high culinary fitness. Something similar has been attempted through IBM Chef Watson (a computational algorithm), which creates novel recipes which has been termed as ‘cognitive cooking’.

With the knowledge of molecular wiring of Indian cuisine, we are putting together a computational framework which will generate recipes that comply with the existing pattern of recipes at the molecular level. This can be leveraged for variety of applications: (a) mobile app that recommends novel recipes, (b) software that complements chefs’ intuition to assist him/her to generate new combinations, and (c) software for creating nutritional recipes with available bioresources. 

Food design
The understanding of molecular nature of accepted food allows us to design new snacks and beverages. These could be tinkered to incorporate new ingredients and flavors to create contrasting compositions. The flavor principle could be applied to learn quintessential features of snacks as a category and to innovate newer snacks. Similarly, beverages such as tea withhold a tremendous commercial potential to synthesize new varieties that are both healthy and receptive to consumers. Composite ingredients such as spices combinations (eg. garam masala) are characteristic of Indian cuisine, and provide opportunity to create divergent combinations. Bioresource that are abundantly available but are not commercially exploited could be used as a base of new food products. Professional chefs and food enthusiasts could a play a big role in increasing the repertoire of recipes and foods as well as towards initial assessment.    

Food as medicine
Indian subcontinent has had a long history of culinary practices in which food has nutritional as well as medicinal value. Ayurveda, the classic medicinal system of India, proposes that food has as much therapeutic value as drugs. There are two ways the discovery of molecular essence of Indian cuisine could help us leverage food as a medicine. One, we could reposition existing food for therapeutic interventions knowing their effect on health. Secondly, at the molecular level, we could hunt for chemical constituents of the food aimed at identification of potential therapeutic agents.

Unhealthy diet is one of the crucial risk factors for noncommunable diseases, such as diabetes and cancer, which kill around 36 million people worldwide each year. Empirical evidence suggests that dietary chemicals act on human genome directly or indirectly, altering gene expression thereby affecting the health. Understanding of molecular composition of the diet, therefore, provides a way to manipulate cell functions through diet. This discovery provides an immense opportunity to identify traditional food that, by virtue of their inherent molecular constitution, could be of medicinal value.

It is worth noting that recent research explorations have been focusing on investigation of molecular constituents we consume on regular basis and their potential effect on health. Natural compounds are known to be good candidates for the drug discovery process. Traditional understanding of healing effects of food ingredients (such as spices) could well be exploited in search of drugs. Such drugs are also expected to have far less adverse drug reactions than synthetic molecules.   

Food tourism
Food shapes the identity of a culture. India is a country with diverse cultures, climates, geographies and cuisines. Interestingly, our research has revealed that despite the differences regional cuisines are similar in their ‘contrasting food pairing’ property. The evolution of regional cuisines seemingly has maintained the unique integrating culinary thread across the apparent diversity. Food can serve as a central theme for tourism with diverse cultures and their rich cuisines serving as centers of attraction. Our work has raised a lot of curiosity about Indian food and the molecular secret behind its taste and its worldwide popularity. This exposure could be leveraged to create an identity for authentic Indian food in contrast to other world cuisines and therefore to develop tourism in India. 

Ganesh Bagler
(This article is to be published in Food and Beverages News magazine)