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RESEARCH AREA

Life Sciences

Reading genomes to tell the future.

 

Overview

The core focus of the life sciences research area team is computational genomics. This involves researching and designing solutions that employ a combination of artificial intelligence, cognitive computing capabilities, robotic process automation, the internet of things, and cloud computing to fully digitize the life sciences value chain.

Fields

The team works across the following areas of research:

  • Human genome variation interpretation: This group works on the development of tools and algorithms in the area of human genome interpretation with DNAseq, RNAseq and epigenetic data analyses. Key collaborative projects include diagnoses of rare disorders of unknown etiology for better understanding of gene pathways and disease pathology, exploration of next-generation sequencing as a replacement for screening tests and genetics in cancer treatment modalities. Another area of research is the construction and use of genotype-phenotype-disease networks using natural language processing to identify novel gene-disease relationships.

The group is led by Dr. Rajgopal Srinivasan and includes Akriti Jain, Poulami Chaudhuri, Sadhna Rana, Sutapa Datta, Uma Sunderam, Aditya Rao, V G Saipradeep, Naveen Sivadasan & Thomas Joseph

Academic Partners: University of California at Berkeley, Tata Medical Center Kolkata

Key Publications:

Adhikari AN, Gallagher RC, Wang Y, Currier RJ, Amatuni G, Bassaganyas L, Chen F, Kundu K, Kvale M, Mooney SD, Nussbaum RL, Randi SS, Sanford J, Shieh JT, Srinivasan R, Sunderam U, Tang H, Vaka D, Zou Y, Koenig BA, Kwok PY, Risch N, Puck JM, Brenner SE. 2020 The role of exome sequencing in newborn screening for inborn errors of metabolism. Nature Medicine (2020) PMID:32778825 doi:10.1038/s41591-020-0966-5

Adhikari AN, Currier RJ, Tang H, Turgeon CT, Nussbaum RL, Srinivasan R, Sunderam U, Kwok PY, Brenner SE, Gavrilov DK, Puck JM, Gallagher R. 2020. Genomic analysis of historical cases with positive newborn screens for short chain acyl-CoA dehydrogenase deficiency shows that a validated second tier biochemical test can replace future sequencing. International Journal of Neonatal Screening, 6(2), 41 doi:10.3390/ijns6020041

Volpi S et al. EXTL3 mutations cause skeletal dysplasia, immune deficiency, and developmental delay. The Journal of Experimental Medicine, 214 (3), 623-637

  • Pan-genome analysis: This team works on developing efficient algorithms to represent a collection of genomes as a graph (pan-genome), and use them for improved modeling and analysis.

The group is led by Dr. Naveen Sivadasan, and includes Kavya Vaddadi, Vidushi Walia, Aditya Ramakrishna Rao, V G Saipradeep, Sujatha Kotte and Thomas Joseph

Key Publications

Rao A, Joseph T, Saipradeep VG, Kotte S, Sivadasan N, Srinivasan R. PRIORI-T: A tool for rare disease gene prioritization using MEDLINE. PLoS ONE. 2020 Apr 21;15(4):e0231728.

Kasak L et al. CAGI SickKids challenges: Assessment of phenotype and variant predictions derived from clinical and genomic data of children with undiagnosed diseases. Human Mutation Jul 19 (2019)

Kavya Vaddadi, Kshitij Tayal, Rajgopal Srinivasan, Naveen Sivadasan. Sequence Alignment on Directed Graphs. Journal of Computational Biology, January 2019. 

Kavya Vaddadi, Rajgopal Srinivasan, Naveen Sivadasan. Read Mapping on Genome Variation Graphs. WABI, September 2019.

Rao A, Saipradeep VG, Joseph T, Kotte S, Sivadasan N, Srinivasan R. Phenotype-driven gene prioritization for rare diseases using graph convolution on heterogeneous networks. BMC Medical Genomics Jul 6;11(1):57 (2018)

  • Metagenomics and systems biology: This group specializes in identifying microbiome-based biomarkers that have clinical application or utility in the early detection or diagnosis of asymptomatic diseases and metabolic or genetic disorders. Modeling and simulation of biological systems that affect different hierarchies of life is also another area of interest

The group is led by Dr. Sharmila Mande and includes Mohammed Monzoorul Haque, Anirban Dutta, Swadha Anand, Kuntal Kumar Bhusan, Chandrani Das, Tungadri Bose, Nishal Kumar Pinna, Sunil Nagpal, Deepak Yadav, Mitali Merchant, Venkata Siva Kumar Reddy Chennareddy, Harrisham Kaur, Rashmi Singh, Vineet Bhatt, Anwesha Mohapatra, Subhrajit Bhar, Arvind Shankar, Krishanu Das Baksi, Preethi Sampath

Academic Partners: AIIMS, New Delhi; ICGEB, New Delhi; NCCS, Pune; IISc, Bangalore; CDFD, Hyderabad; Bose Institute, Kolkata; IISER, Mohali; IIT Bombay; IIT Kharagpur; MDRF, Chennai; NCL, Pune; NII, New Delhi; THSTI, Gurgaon; University of Hyderabad; University of Copenhagen

  • Computational structural biology: This team is working on:

  1. Using multi-scale modelling and simulation to obtain fundamental insights into the structural dynamics of biomolecules (especially drug targets)

  2. Applying deep learning and other AI-based methods for drug discovery

  3. Using network-based methods for drug target identification and drug repurposing.

The team is led by Dr. Arijit Roy, and includes Dr. Siladitya Padhi, Dr. Navneet Bung, Dr. Broto Chakrabarty, Dibyajyoti Das, and Sowmya Ramaswamy Krishnan.

Academic Collaborations: University of Oxford, Oxford, UK; Icahn School of Medicine, New York, USA; Dr. Reddy’s Institute of Life Sciences, Hyderabad, India; International Institute of Information Technology, Hyderabad, India; University of Hyderabad, Hyderabad, India

Key Publications:

(1) Bailey HJ, Bezerra GA, Marcero JR, Padhi S, Foster WR, Rembeza E, Roy A, Bishop DF, Desnick RJ, Bulusu G, Dailey HA, Yue WW (2020) Human aminolevulinate synthase structure reveals a eukaryotic-specific autoinhibitory loop regulating substrate binding and product release. Nat Commun 11(1):1-2.

(2) Das D, Krishnan SR, Roy A, Bulusu G (2019) A network-based approach reveals novel invasion and Maurer’s cleft-related proteins in Plasmodium falciparum. Mol Omics 15(6):431-441.

(3) Das D, Krishnan S R, Bulusu G, Roy A (2019) Computational predictions of host-pathogen interactions using domain and sequence signature. 2019 IEEE International Conference on Bioinformatics and Biomedicine, San Diego, USA.

(4) Bung N, Roy A, Chen B, Das D, Pradhan M, Yasuda M, New MI, Desnick RJ, Bulusu G (2018) Human hydroxymethylbilane synthase: Molecular dynamics of the pyrrole chain elongation identifies step-specific residues that cause AIP. Proc Natl Acad Sci USA 115(17): E4071-E4080.

(5) Bung N, Surepalli S, Seshadri S, Patel S, Peddasomayajula S, Kummari LK, Kumar ST, Babu PP, Parsa KVL, Poondra RR, Bulusu G, Misra P (2018) 2-[2-(4-(trifluoromethyl) phenylamino) thiazol-4-yl] acetic acid (Activator-3) is a potent activator of AMPK. Sci Rep 8(1):1-16.

  • Model-informed drug discovery and development: This performs research in the following areas: 1) PK-PD Data Analyses 2) Drug safety Prediction and Drug Repurposing based on clinical side effects, gene expressions and other types of drug related information. Furthermore, they develop tools that incorporate accurate models to estimate the viability of candidate drug molecules and to discard unviable molecules as early as possible in the drug discovery and development process

The group is led by Dr. R Narayanan (Principal Scientist) and includes Ibrahim Roshan, Mastan, Shyam Sundar Das, Amit Patil and Pritish Ranjan

  • Patents and publications (2016 onwards): This research area team has received three patents and has had its work published in over 30 conferences, workshops, and journals

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