India remains on-board in exploring the human proteome

Fifteen years ago, India missed the human genome bus. But a bunch of 50-odd young Indian researchers, mostly from Bangalore, has now ensured that India remains on-board in exploring the human proteome – the next big thing in biology that promises to change the medical landscape.

Proteome is a comprehensive map of all human proteins responsible for different biological functions in the body.

The young team was led by Akhilesh Pandey, a professor at Johns Hopkins University School of Medicine, who set up the Institute of Bioinformatics in Bangalore. Son of an Indian Air Force officer, Pandey was born in Dibrugarh and grew up in Delhi, Kanpur, Varanasi, Mumbai, Deolali, Bangalore and Chennai because of his father's transfers. He wanted to pursue a research career in the military but eventually opted out for higher studies in the University of Michigan, Harvard Medical School and Massachusetts Institute of Technology. Pandey spoke to Deccan Herald's Kalyan Ray on the research and its implications.

Excerpts:
The proteome map is coming out almost 15 years after the human genome map -- what is its significance?

The human genome was a very well organised and well funded effort with significant community participation. A similar analysis of the human proteome has been challenging for a number of reasons that including lack of funding and lack of a consensus regarding the approach to be used for characterising the proteome. Given that mass spectrometry-based technologies are quite mature, we simply used the best available mass spectrometers to carry out a systematic analysis of a variety of normal human organs and cell types. This is the largest single proteomic data set for any organism. Thus, we now have a reference for the normal human proteome, which is significant because although DNA provides instructions for making the proteins, ultimately it is the proteins that are responsible for all biological processes in cells and tissues. Importantly, the genome only provided an estimate for genes – we now know for sure which parts of the human genome truly code for proteins.
Did you find out anything unexpected?

The unexpected findings mainly related to what was incorrectly predicted about protein-coding parts of the human genome. We found regions that were designated as ‘noncoding RNAs’ and ‘pseudogenes’ that we found to be translated (i.e. made into proteins). This suggests that: (i) we do not yet have a thorough understanding of how our own genome works; and, (ii) we could learn from this type of unbiased data and reformulate the ‘rules’ of biology that have been defined by us. We also found a number of proteins that were hitherto labeled as ‘hypothetical’ to have very interesting pattern of expression in organs and cells.
Will it improve the medical science in future?

Yes, a knowledge of organ-specific proteins could provide a list of potential biomarkers that could be used for detection of diseases arising from those organs by using simple test such as a blood test. Drug companies will be able to use the location of each protein to understand and to explain side effects of drugs. Finally, having a map of normal human tissues will facilitate analysis of tissues when they are affected by diseases.
Are the functions of some of these proteins already known? What additional knowledge would this discovery bring to the table?

The functions of roughly half of the human proteins are not really understood. Based on this map, we now know which protein is located where and which proteins are restricted to one organ or cell type – this information is not encoded in the genome and can provide clues to biologists to elucidate the function of individual proteins.
It is widely stated India missed the human genome bus -- will it be right to say that Indians are on board with the proteome project?

You are absolutely right about missing the bus on the human genome project! This work took us over two years to complete and half of all of the work was done in Bangalore at IOB. Without this crucial component, we would not have been able to achieve this goal. This is truly a matter of pride for science and scientists in India. Although India did not participate in the human genome project, completion of a human proteome map by this team now puts India at the forefront of the international efforts to characterise the human proteome.
What's the difference between your paper and the second paper from the German group in the same issue of Nature?

We were not aware of any other effort to define the human proteome using mass spectrometry to profile normal human tissues. Thus it is truly a coincidence that work by Kuster et al is being published simultaneously with our study. The data sets are complementary in many ways and the research community now has the advantage of referring to multiple lines of evidence for each protein, coming from independent laboratories.

One of the fundamental differences between our studies is that we have used a single mass spectrometry platform and data analysis pipeline to generate our data while Kuster and colleagues have assimilated publicly available heterogeneous data sets, generated on different mass spectrometry platforms from multiple labs, in addition to generating some of their own proteomic data.

Our data was generated using only normal tissues and cells whereas Kuster and colleagues have combined data from both cancer cell lines and normal tissues. Our study also employed a novel analysis strategy that made it possible for us to discover many novel proteins produced by alternate open reading frames and ‘pseudogenes’. It will be interesting to compare our datasets to extend our understanding of the human proteome.

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