Debasis Dash, PhD

Dr Dash, an indigenously grown scientist, who had the courage to address major global challenges with limited computational resources but using extremely innovative ideas and algorithms to make a global impact and able to establish a vibrant school in the area of genome informatics. Dr Debasis Dash trained as a biophysicist self-learned genome sequence analysis in late 90’s, when genome sequences have just started to appear in public domain. Using innovative ideas he addressed major global challenges with limited computational resources when India was under sanction and did not have access to multiprocessor computers. Inspite of these difficulties, he has made outstanding contribution by brilliantly interfacing experimental functional genomics with in silico biology. He has developed various award winning (Banglore Bio 2005, 2006 best product presentation) commercialized software suits (PLHost, Genocluster etc.) using entirely original concepts that has led to the recognition of invariant peptides as specific functional signatures. These software suits are effective in identifying the most susceptible sites for mutations resulting in disease phenotypes in humans. These tools are used by 33 R&D institutes, educational institutes, universities & colleges in the country including IISc, BARC, Pune University, MKU, CSIR labs and internationally by RIKEN, Japan. Utilizing the PLHost tool, his collaborators have identified INO- 80, novel genes coding for chromatin remodeling proteins [BBRC, 2004], which has been reported in the prestigious Online Mendelian Inheritance in Man (OMIM) (http://www.omim.org/entry/610169). Using PLHost and CoPS (Comprehensive Peptide Signature database) [Bioinformatics, 2004] he assigned function to large number of unknown hypothetical proteins in bacterial and human genome and deciphered the role of these invariant peptide signatures as folding nucleus [JMB, 2005] of proteins that could be potential drug targets in M. tubeculosis. This was the genesis of the famous, globally visible Open Source Drug Discovery project (www.osdd.net).

His unique algorithm of GeneD’cipher has identified three novel genes in SARS virus [Bioinformatics, 2004] that helped in diagnosis during outbreak in China. This outstanding contribution was covered by all major media reports such as, “Indian scientists find three new genes of SARS”, Economic Times Dec 30, 2003; Indians find SARS virus genes, The Hindu, Dec30, 2003; "Gene Decipher" that can analyze small genomes with ease. Using this software, the scientists have identified three new SARS genes which apparently have critical functions in the virus”, India Today, January 19, 2004 etc. Dr Debasis has been instrumental in setting up of the GN Ramachandran Knowledge Centre for Genome Informatics at IGIB. Over the last one and half decade, he grew up with the field of genome sequencing, variation analysis to proteomics. He has mastered himself in analyzing high throughput data in making biological discovery. He has extensively and successfully collaborated with several experimental biologists by providing insights into functional genomics. Given below is the impact of his contribution to the field of biological sciences.

Genomics:

Dr Debasis played a central role of data analysis to database creation in the Indian Genome Variation Consortium, which is largest study conducted on healthy individuals to catalogue basal genomic variation in India in terms of its population and genomics coverage. Thegene-mapping study catalogued genes, involved in cancer, ageing, eye-diseases, cardiovascular disorders, and neuro-psychiatric disorders and analyzed variations within these genes among the sample population. The Indian Genome Variation Consortium project provided the first comprehensive genetic landscape of the Indian population [Hum Genetics, 2005, J of Genetics, 2008, Database, 2010]. The consortium has generated data on genome wide neutral SNPs as well as informative SNPs from 1000 genes implicated in diseases and drug response in 55 diverse Indian populations and provides a framework for carrying out genetic studies of diseases prevalent in India (http://www.igvdb.res.in). This was one of the largest projects in biological science in India and led to the capacity building in genomics in a number of collaborating institutes as well as global visibility (Nature Review Genetics 2008). Dr. Debasis has himself participated in identifying copy number variations as well as unique admixture events and signatures of selections using this variation data [Am J Hum Genet, 2011, Human Genet, 2012, Genome Biol Evol, 2014]. This data has also been used to identify predictive markers in high altitude adaptation, markers for susceptibility to infectious diseases, tracing human migrations and history of diseases as well as identifying founders for diseases. Due to his contribution in these projects he has been acknowledged as an author as a Indian Genome Variation consortium member in 37 publications many of which have been published in prestigious peer reviewed journals like Science, PNAS, PloS Genetics, Molecular Biology and Evolution etc. In fact, he is the only scientist from India, who has contributed actively in the global effort of development of Phenotype and Genotype Experiment Object Model (PaGE-OM) [Hum Mut,2009] for the interoperability of biological data among various databases (eg., dbSNP, jSNP, Alfred, HGVbase etc.) and HGVBaseG2P [NAR, 2009]. Dr Debasis is the only Indian scientist in a team of 22 from Stanford University, Yale University, USA, DNA Data Bank of Japan, RIKEN, Tokyo Institute of Technology, Japan, Institute for Molecular Medicine Finland (FIMM), Finland, University College London (UCL), and University of Leicester, UK representing 9 countries who proposed PaGE-OM. His work positioned CSIR-IGIB among the leading bioinformatics institutions of the world.

The success and visibility of the IGV project also led IGIB to host the XIII th International Human Genome Meeting in 2008. India was the third country after Japan and China to host this event in Asia and this reflected our positioning in genomics era. Indian Genome Variation project has featured in many International journals and also had a major coverage in leading newspapers and magazines. (http://www.igvdb.res.in/media.php).

Dr Dash in the last 7-8 years has concentrated his efforts in the area of next generation sequencing analysis specifically with a focus on helping clinicians identify novel mutations through exome sequencing analysis. The first clinical exome sequencing in collaboration with AIIMS led to identification of novel mutation in spinocerebellar ataxia in India (Clinical genetics, 2014). The pipeline for exome sequencing is now being extensively used for identification and creation of diagnostic panels for a multitude of disease by clinicians across the country. Dr Dash is also heading the informatics group in a new multidisciplinary initiative of Ayurgenomics that aims to integrate Ayurveda and Genomics for predictive and personalized medicine. This project involves phenomic stratification of thousands of individuals from diverse cohorts across the country. A large number of omics technologies for studying exomes, transcriptomes and metagenomes are being used to study subjects, where Dr Dash is a lead member involved in development of pipelines as well as machine-learning methods for carrying out integrative analysis of large scale multi- dimensional data.

Proteomics:

Dr Debasis and his research group have shown various functional roles of intrinsically disordered proteins (IDPs). He is the first person to associate IDPs with PEST motifs-responsible for protein degradation and explained how conformational flexibility allows multiple cellular interactions (PROTEINS: Structure, Function, and Bioinformatics, 2006). His unique work of revealing role IDPs in transient interaction (PROTEINS: Structure, Function, and Bioinformatics, 2007) alone has been cited more than 120 times. His work on unraveling the potential of intrinsically disordered proteins as drug targets: application to Mycobacterium tuberculosis has led to identification of GlmU as a potential target [Mol Biosyst, 2009]. Further, he in collaboration developed a webserver for finding inhibitors for GlmU [BMC Pharmacology,2011].

Proteogenomics:

Dr Debasis realizing the need for development of peptide spectral matching (PSM) algorithm as there were many unassigned spectra in the database, developed MassWiz [J Prot Res, 2011]. It is only PSM scorer from the country and has been recognized by MIT Technology Review (TR35 innovation from India, 2013 ) and have honored his student among young innovators whose inventions and research they find most exciting. He and his team have developed open source computational algorithms and associated software suites, MassWiz, flexifdr [PloS one, 2012] and ProteoStats [Bioinformatics, 2013] which enable low-cost, high accuracy proteomics data mining and analysis. He was invited as a visiting faculty to Johns Hopkins Medical Institute, USA in Indo-US S&T fellowship program. Combining his strength in genomics and proteomics, Dr Debasis has made several discoveries in proteogenomics. Most notably, his systematic analysis of proteomics data using multiple algorithms have resulted in discovery of 101 proteins in human plasma [PloS one, 2011], 41 gene products in M. tuberculosis [MCP, 2011], 59 proteins in agriculturally important symbiont B. Japonicum [MCP, 2013], 28 proteins in human pathogen S. flexinery, most importantly, 28 proteoforms in human missing proteome [J Prot Res, 2015] and 27 splice variants & 15 non-coding exons in Rattus norvegicus microglia [MCP, 2016]. In order to streamline the process of this novel discovery and ease of use by experimental biologist, he has developed in house pipelines such as GenoSuite and EuGenosuite for high throughput proteomics data analysis. His visibility in the field of proteogenomics fetched his student prestigious Australian Endeavour fellowship and paved the way to work in world famous Queensland Institute of Medical Research, Brisbane. This led to the identification of more than 170 toxin proteins in the box jellyfish, Chironex fleckeri, [BMC Genomics, 2015] the largest and most dangerous cubozoan jellyfish to humans through collaborative research. Findings from this work are highlighted by Christie Wilcox, in Science Sushi, June 2, 2015. Few excerpts are “Despite the economic and medical impact that this jellyfish has on Australia (and similar species worldwide) we know very little about what is exactly in the venom,” ....The team’s goal was to perform the most in-depth analysis of Chironex venom to date, producing both a proteome (a library of the proteins present) and a transcriptome (a library of which genes are expressed).”

Dr Dash has been invited to many international conferences as speaker, which demonstrates his enormous scientific contribution in the field. The largest contribution, in my opinion, Dr Dash’s work has made is creation of a vibrant school of genome informatics in India and many of his trained students have received prestigious fellowships like Welcome Trust, IYBA, D.S. Kothari and are faculties at IIT, IISER, THSTI, Delhi University. In short, work of Dr. Dash has made a major impact in an emerging field of new biology as his work has received over 1700 citations in scholarly articles.