Structural and functional impacts of Human proteins harboring disease mutations: We have been exploring how known disease-causing mutations impact protein structure, hence, their molecular functions and further, their interactions with the other biomolecules. Our past studies resulted in the development of a computational tool called HANSA for prediction of functional impact of disease-causing missense mutations in human proteins. We were part of collaborative studies where we had investigated effects of several disease-causing mutations on the protein harboring them. Currently we are investigating Loss-of-Function as well as Gain-of-Function mutations in human proteins.
Molecular properties of centrally important proteins in protein-protein interaction networks: Protein-protein interaction networks are characterized by the presence of few proteins with high degree, betweenness and other centrality values. When tissue-specific protein-protein interactions were analysed we could find a dichotomy among the highly connected proteins (hubs). Some of the highly connected proteins are expressed in very tissues and cell types and hence designated as “local hubs” and some others are universally expressed in most of the tissues and hence were designated as “global hubs”. These two categories of proteins show distinct molecular and functional proteins. Similarly, we also found trichotomy among the proteins with high degree and high betweenness values which we referred to as pure-hubs, pure-bottlenecks and hub-bottlenecks
Metagenome analyses of environmental microbiomes: We investigate relationships between microbiome profiles and their habitats. We are currently analyzing metagenomes of the human gut microbiota. We are also analyzing marine microbiomes. The analyses include microbial diversities, co-existing microbial communities and their functional biopathways.
Deciphering the human "dark proteome" - structure and functions of non-canonical peptides and small proteins: Traditionally, the definition of a proteome of a living organism has been restricted to all the canonical proteins expressed from the major isoforms of annotated genes largely discounting the large pool of peptides and small proteins of non-canonical origin that are the products of transcripts borne out of alternative splicing mechanism and also the products of upstream ORFs (uORFs), downstream ORFs (dORFs), overlapping ORFs (oORFs), and even long non-coding RNAs (lncRNAs) or untranslated regions (UTRs) of mRNAs. As the data are increasingly available for the proteins/peptides of non-canonical origin, we have emarked on characterising such peptides/proteins for structure and functions in an attempt to throw some light on the dark side of the functional proteome.