“The completion of the Human Genome Project Is A Milestone Not Just For Science But For Humanity Itself.”

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Since the completion of Human Genome Project (HGP) efforts are on to investigate all the human proteins. On October 19, 2020, the international Human Proteome Organization (HUPO) released the draft human proteome at the 19th Human Proteome Organization World Congress, connecting virtually, with this Virtual Issue of the Journal of Proteome Research, “Celebrating 90% Completion of the Human Proteome”.

These findings will be valuable for the future biomedical science discovery and precision medicine.

On a more technical side, the number of protein-coding genes from HGP was estimated to be >100,000 but now this number is ~19,700 with recent HGP draft release. The protein-coding genes estimated from neXtProt’s 2020 release are 19,773. However, credible PE1 evidence (at least nine amino acid residues long, peptides non-nested, FDR at peptide and protein levels 1%), for 90.4% of the human proteome (17,874 PE1s from the 19,773).

League of India talks with Dr Sanjeeva Srivastava about the development. Dr Srivastava serves on the Executive Council of Human Proteome Organization (HUPO) and Proteomics Society, India (PSI). He is also the man behind one of the first-ever documentaries on proteomics – “Proteomics: Translating the Code of Life” and “Human Proteome Project (HPP)”.

Also Read: COVID-19 Dialogue: “Like Humans, Microbes Too Find Newer Ways To Survive And Thrive”

How the advancement of technology has helped to unravel the Human Genome to Human Proteome?

Dr Srivastava: 13-year-long effort from 1990 to 2003 has determined the human genome for the very first time. The completion of the Human Genome Project is a milestone in humanity and science. The initiative has opened and motivated thinkers and scientific forums all over the world which has eventually introduced Proteomics to investigate the total proteome.

The initiative was triggered by the thinking that a genomic map followed by proteome map could unravel different complex human disease progression.

An effort has been made from Akhilesh Pandey and his team to elucidate the human proteome map using Mass Spectrometry based proteomics for the very first time in 2014. The study has identified proteins encoded by 17,294 which accounts for around 84% of the total annotated protein-coding genes in humans. This publication has opened a window for the multiple new publications that have unravelled proteome of different organs and tissues of Human.

The huge boom in proteomics has enriched the publicly available databases like Nextprot, Human Proteome Atlas and Peptide Atlas.

The worldwide collaborations and efforts from the scientific community could represent 89% of all 19, 823 coding genes published in 2019 Metrics from the HUPO Human Proteome Project. The same publication also reported that the missing protein has been reduced from 2949 to 2129 since 2016.

The recent publication “A high-stringency blueprint of the human proteome” published in 2020 reported a 90.4% complete high-stringency human proteome. This report has mentioned that a confident detection of Human Proteome has risen from 69.8% in 2011 to 90.4% in 2020.

But the decrease in the missing protein identification with the course of time could lead to an understanding that confident identification of the other 1899 missing proteins might be difficult.

How the unravelling of 90.4% of human proteome can help in understanding disease biology? How the Human Proteome Projects could open new opportunity in research?

Dr Srivastava: The understanding and diagnosis of a disease progression are massively dependent on the alteration of the human proteome. The early biomarker detection could help diagnosis of complex diseases and curing it in the primary phase. Even the understanding the disease progression and unravelling the therapeutic modalities are also dependent on human proteome information.

The enrichment of human proteome and its expression in normal healthy tissue is very important to understand the alteration of that particular protein in the biological disorder.

In our lab, we do face this hurdle and understood the crucial role of healthy tissue and basal level protein expression in biomarker identification.

A global initiative like HGP (Human Genome Project) and HPP (Human Proteome Project) from a long time has taken initiatives to understand the molecular mechanism underlying health and diseases. The human proteome project has introduced Biology/Disease-driven Human Proteome Project (B/D-HPP) which could focus on disease research and understand the biology behind it.

The enrichment and understanding of human proteome could not only accelerate disease biology research but could improve the confidence level of biomarker identification.

We are proud to represent India in this milestone paper, which was published recently in Nature Communications here: https://www.nature.com/articles/s41467-020-19045-9

How India as a country is contributing to the Human Proteome Project? What is the role of Indian scientists in understanding the disease biology using proteomics?

Dr Srivastava: India being a blooming country in science and technology has taken multiple initiatives and excel in a different arena. Looking at the current scenario in COVID pandemic, I feel proud to say that Indian scientists and community has really shown their positivity in fighting this sudden viral attack. Labs from different states have managed to help in some or the other way.

On one hand, I found labs who have come forward and trying to understand the biology of COVID infection to help healthcare sector for better diagnosis whereas on the other hand scientists have tried to make innovative gadgets and techniques to deal with this pandemic.

With the same spirit, I believe that many labs from India will contribute more in the Human Proteome Project and disease biology.

India has entered the CPTAC (Clinical Proteomic Tumor Analysis Consortium) in 2016 under the leadership of IIT Bombay and Tata Memorial Cancer Hospital, Mumbai.

It’s being a decade that my lab is working closely with many clinicians and industry in Brain Tumors link Meningioma, Glioblastoma, Medulloblastoma and infectious diseases like Malaria and Dengue. We have tried different approaches to understand these complete diseases based primarily on proteomics. I believe in coming days we can deliver more in terms of translational research and help health care sectors more precisely.

My lab is also working in a collaborative project under HUPO which aims to deliver the neuroanatomical region and inter-hemispheric region-based human brain proteome which can accelerate the research in neuroscience.

Recently one of our research work on malaria proteomics is published in Communications Biology – Nature here: https://www.nature.com/articles/s42003-020-01384-4

What could be the future steps that HUPO can take in the light of the Human Proteome Project? What is your take-home message for the young researchers and scientists?

Dr Srivastava: It is true that the worldwide effort has helped in the unravelling of 90.4% of human proteome but still we need to achieve the missing proteome too. I do believe that getting confident identification of left-over missing proteome will be accomplished. This challenge of left-over missing protein identification could lead to introducing new experimental strategies and also the advancement of mass spectrometry.

On the other hand, the post-translational modification plays an important role in disease biology and understanding the molecular mechanism. This could be another arena where Human Proteome project might intervene.

Together with this, HUPO aims to unravel the functions of many unknown proteins, development of multi-omics technologies, expansion of many sub-domains of HPP and improving biobank facilities. I personally believe and experienced, when experts from different arenas sit together to solve a problem, it not only works and better but also opens new windows.

I will suggest that India should come up and understand the power of proteogenomics collaborations in science, which could introduce multi-institute projects, big-data analysis centres and biobanks to work on complex diseases like cancer as well as wellness of healthy individuals.

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