India needs focused, sustained policies to promote translational research in proteomics

India is on the edge of a remarkable evolution in proteomic science with dramatic expansion taking place in the last decade. Despite success stories, India is yet to realise successful translation of laboratory findings into clinical practice. In conversation

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Dr Ashok Kumar Mohanty, Principal Scientist, NDRI

What is the current status of India in proteomics research?
Indian researchers have been a major contributor in drafting the "human proteome map" along with international teams. Currently, more than 100 research/academic institutes are involved in core proteomics research across India. In addition to this, labs training courses, e-learning proteomics courses and remote triggered proteomics programmes are organised by institutes/private companies to educate people regarding advancement in instrument, method development and data analysis. The establishment of Proteomics Society, India (PSI) has created a platform for Indian proteomics researchers to share ideas, hold research collaborations, besides conducting annual conferences and workshops.

What are some of the recent developments in this field?
The ultimate aim of proteomics is to fully identify and quantify the entire complement of genes and post-translational modifications in biological samples of interest. For the past 15 years, liquid chromatography-tandem mass spectrometry (LC-MS/MS) in data-dependent acquisition (DDA) mode has been the standard for proteomics when sampling breadth and discovery are the main objectives; multiple reaction monitoring (MRM) LC-MS/MS has been the standard for targeted proteomics when precise quantification, reproducibility, and validation are the main objectives. Recently, improvements in mass spectrometer design and bioinformatics algorithms have resulted in the rediscovery and development of another sampling method: data-independent acquisition (DIA). Currently, DIA approaches the identification breadth of DDA while achieving the reproducible quantification characteristic of MRM or its newest version, parallel reaction monitoring (PRM). DIA is still a work in progress towards the goal of sensitive, reproducible, and precise quantification without external spectral libraries. New software tools applied to DIA analysis have to deal with deconvolution of complex spectra as well as proper filtering of false positives and false negatives. However, the future outlook is positive, and various researchers are working on novel bioinformatics techniques to address these issues and increase the reproducibility, fidelity, and identification breadth of DIA.

Proteomics is taking key position in biology and biomedical research. How crucial is the role of proteomics research in diagnosis and treatment of major human diseases?
Most of the attention on infectious diseases of the developing world has focused on the development of rapid diagnostic tests and novel therapeutics to ensure timely treatment and improved survival rates. For over a decade now, several attempts to discover novel biomarkers in human bio-fluids such as serum, plasma and urine have been made by various research groups. Such studies have involved the use of proteomic technologies to profile host responses to infectious diseases. The high-throughput proteomic technology platforms not only investigate the systemic alterations of protein expression in response to diseases but also enable visualisation of the underlying interconnecting protein networks and signalling pathways, facilitating the discovery of unique markers of infection. One of the first attempts to unravel the proteome of the malaria parasite Plasmodium vivax from clinical samples provided new leads towards the identification of diagnostic markers, novel therapeutic targets and an enhanced understanding of malaria pathogenesis.

Similarly, analysis of serum proteome of dengue and leptospirosis patients has led to the identification of unique protein signatures and molecular targets. A comparative serum proteomic analysis of severe and non-severe malaria in search of prognostic markers using quantitative proteomics has highlighted the presence of muscular, cytoskeletal and anti-oxidant proteins in patient sera revealing extensive oxidative stress and cellular damage in severe malaria. These findings are currently being validated in a larger cohort of patients using immunoassays. The application of proteomic technologies has shown promising leads. However, early disease detection, measurement of therapeutic efficacy, prediction of disease severity and tailored patient therapy are still some distance away.

India is playing an increasingly significant role in global proteomics research in the post-genomic era. What are your views?
Although the development of proteomics research in India was rather slow at the outset, the last decade or so has seen a dramatic expansion in the proteomics community. The most important application of proteomics is believed to be discovery of disease biomarkers and drug targets which can lead to designing of products aimed at diagnosis and treatment of diseases like cancer, cardiovascular diseases, obesity and type 2 diabetes. A lot of laboratories in India are focussing deeply into proteomic research in the area of human biology, agriculture, disease diagnosis, animal sciences including fisheries. India has taken a lead to advance proteomic research in collaboration with world communities for which Proteomic Society of India is playing a big role.

 

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