Research Activities
Theoretical studies of biological systems
We study biological systems at levels ranging from ecological to genetic. Along with models in tissue pattern formation in Developmental Biology and population dynamics in Ecology and Epidemiology, we also are involved in computational genome analysis, reconstruction and analysis of intracellular biochemical networks, protein contact networks, development of tools and databases, as well as innovation of new theoretical methods, algorithms, and software tools that can be used to harness bioinformatic information.
1.1. Genome Analysis:
High genetic diversity in the human immunodeficiency virus, HIV type 1, responsible for the world-wide pandemic of AIDS, has led to the existence of different variants or subtypes prevalent in different parts of the world, which display differential infectivity and transmissibility. Accurate classifications of isolates are thus important for monitoring the epidemic and are vital for effective drug therapy. Phylogenetic methods based on the comparison of genes and parts of genomes have sometimes yielded incorrect results. However, no simple methodology exists that can directly classify HIV-1 subtype from the complete genome sequence. We developed an alignment-free method using the Chaos Game Representation (CGR) to map the genome on a 2D plot and identify the distinctive genomic signature associated with the genetic sequence organization in different HIV-1 subtypes. Nucleotide word lengths (2 to 8) on HIV-1 group M genomes were analyzed, and optimum word length of 6, could classify HIV-1 subtypes. Using the optimized word length, we showed accurate classification of the HIV-1 subtypes from both the Reference Set sequences and available sequences in the database. We also predicted the subtypes of five unclassified HIV-1 sequences from Africa and Europe. Thus, CGR is a simple and computationally less intensive genomic signature-based approach, which when used with suitable word length optimization, can be applied to classify intra-species variations. We propose that it will be useful in subtype annotation of the newly sequenced HIV-1 genomes [1]. Base compositional organisation in genomes has been shown to have a multi-fractal structure indicating involvement of multiple length scales. We have used the spectral properties of the HTLV, HIV-1, HIV-2, and SIV genomes and shown that these properties can segregate the genomes to different clusters [2].
Researcher(s):
- Dr. Somdatta Sinha & Group
1.2. Biochemical networks:
Cellular functions are carried out by large, highly interconnected networks of biochemical pathways. Thus perturbations in one pathway can propagate to other pathways and affect the overall cellular behavior in an unpredictable manner. We have been involved in large scale reconstruction and analysis of biochemical pathways of whole organisms from existing databases to understand the common design principles, structure and evolution of pathways, enzymes and genes involved. We are using such methods to study important pathways implicated in cancer, using flux balance analysis (FBA) and other methods. We have also developed a web-based resource, called ORBiP (On-line Resource on Biochemical Pathways) for studying biochemical pathways.
Researcher(s):
- Dr. Somdatta Sinha & Group