Ø  The exchange of information between organs and tissues is critical for proper functioning & survival of all living organisms

Ø  This allows organisms to adapt to changes in the environment, assess energy reserves & maintain overall well-being.

Ø  ‘Multicens’ will help uncover key molecular mediators of inter-organ communication.

CHENNAI, 25^th July 2023: Indian Institute of Technology Madras (IIT Madras) scientists at the Robert Bosch Centre for Data Science and Artificial Intelligence (RBC-DSAI) have developed a computational approach called ‘MultiCens’ to understand the interactions between genes that are responsible for inter-organ communication within the body.

Communication among cells in different tissues and organs is pivotal to multicellular life. Molecular basis of such communication has long been studied, but genome-wide screens for genes and other biomolecules mediating tissue-tissue signaling are lacking.

To systematically identify inter-tissue mediators, IIT Madras researchers developed ‘MultiCens’ (Multilayer/Multi-tissue network Centrality measures). The exchange of information between organs and tissues of the body is critical for the proper functioning and survival of all living organisms.

This inter-organ communication network (ICN) allows organisms to adapt to changes in their environment, assess their energy reserves, and maintain overall well-being. This research represents a significant advance in the development of methods to understand inter-organ communication and its implications.

Many molecules including hormones, gut microbiota produced metabolites, etc., serve as messengers in the ICN process. They affect key decisions such as growth, survival, and regulated cell death. Previous studies, mostly conducted on model organisms like fruit flies, have revealed highly complex ICNs.

The findings of this research have been published in the reputed peer-reviewed journal PLOS Computational Biology (https://doi.org/10.1371/journal.pcbi.1011022). The paper was co-authored by IIT Madras researchers Dr. Tarun Kumar, Dr. Sanga Mitra, Prof. B. Ravindran and Prof. Manikandan Narayanan, along with Intel Corporation researcher Dr. Ramanathan Sethuraman, who closely and actively collaborated together with the IIT Madras team towards this research.

Highlighting the important applications of this research, Prof. B. Ravindran, Mindtree Faculty Fellow and Head, RBC-DSAI, IIT Madras, said, “Much of the research on the Inter-organ Communication Network (ICN) has primarily involved experiments on model organisms like the fruit fly, which may not directly apply to humans and other non-model organisms. Moreover, the experimental techniques used can be time-consuming due to the numerous interactions between biomolecules in different tissues. As a result, our knowledge of the ICN is currently incomplete.”

Prof. B. Ravindran, who is also a faculty in the Department of Computer Science and Engineering, IIT Madras, added, “There is thus, a need for alternate methods of analysing ICNs in order to gain a comprehensive understanding of their role in maintaining good health and addressing diseases.”

The researchers from IIT Madras have created an innovative computational method to study the connections between the genes responsible for different organs and tissues. They utilized the genomic information available for various tissues to develop a method called ‘MultiCens.’ There are several research applications of this tool.

Elaborating further on the significance of this research, Prof. Manikandan Narayanan, faculty in the Department of Computer Science and Engineering at IIT Madras, a DBT/Wellcome Trust India Alliance Fellow, and corresponding author of the study said, “The importance of our MultiCens method lies in its ability to identify the key genes in the ICN in various healthy or disease conditions. At the heart of MultiCens are network science algorithms that quantify the importance of genes within a tissue as well as across multiple tissues in a hierarchical fashion.  This method was developed as a focused team effort among all authors of the paper, with especially close interactions between the members in my Bioinformatics and Integrative Data Science (BIRDS) lab - Dr. Tarun Kumar, then a PhD student, and Dr. Sanga Mitra, a senior project scientist”.

Dr. Tarun Kumar with his expertise in algorithms for rich graph structures added that “Using algorithms for computing multi-layer network centrality measures, which are extended from traditional single-layer network centrality algorithms, we examined the relationships among genes that interact within and between tissues, and identified the key genes involved in communication between different parts of the body.”

Dr. Sanga Mitra, a seasoned researcher in applications of bioinformatics methods and biological interpretation of the resulting predictions added, “We explored applications of MultiCens in two diverse settings – in one setting, we predicted genes closely associated with hormones, which are essential for numerous bodily functions; and in another, we unveiled changes in gene interactions within and across different brain regions affected by Alzheimer's disease.” The application can be further expanded to understanding cancer metastasis, as cancer originates in a single organ and in due course of time spreads to others.

Dr. Ramanathan Sethuraman, Healthcare Architect and Principal Engineer at Intel and co-author of this work explained, “Understanding the molecular pathway for disease manifestation and to identify the causal targets are of prime importance in any disease management. MultiCens is a step in this research direction.”

MultiCens can be applied to other healthy and disease genomic settings as well. MultiCens source code is openly available, and ongoing work on web interface to the method and experimental validation of its predictions can further enable a comprehensive understanding of the ICN and its role in overall health and well-being.”

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