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Mapped: largest range of proteins

New Delhi, May 28: An international research consortium led by Indian scientists has generated a catalogue of 17,294 proteins, a draft proteome map that could be a second big leap towards deciphering the body’s mechanisms, after the completion of the human genome sequencing effort in 2003.

The draft map covers 84 per cent of proteins coded by human genes and is the most comprehensive list of proteins in the human body crafted from scratch using blood cells and tissues from [ ] adults and foetuses, the scientists have said.

The study led by scientists at the Johns Hopkins University School of Medicine in Baltimore, US, and the Institute of Bioinformatics (IOB), Bangalore, has also discovered 2,535 so-called “missing proteins”, predicted to exist in the past by others but never observed. It has also found 200 new proteins that had not even been predicted before.

“We can now say with far greater accuracy than ever before which proteins are found in which human tissues or organs,” Akhilesh Pandey, professor of genetic medicine at Johns Hopkins and principal investigator of the study, told The Telegraph. “This is critical to understanding how the human body works at the molecular level.”

Pandey and his colleagues have described their draft proteome map in a paper set to appear in the journal Nature on Thursday. While a global consortium of scientists had completed sequencing the human genome in 2003, biologists have since then been trying to put together a giant map of the proteins that each gene codes.

Scientists who have not been directly associated with the Baltimore-Bangalore proteome-mapping effort that took a little over two years are calling it a landmark feat.

“This is an extraordinary collection of sets of data on which hypotheses of human biology in health and disease can be tested,” said Krishnaswamy VijayRaghavan, the secretary in the Centre’s department of biotechnology (DBT) that contributed funds for the study.

Study team member Harsha Gowda at the Institute of Bioinformatics in Bangalore

Proteins, which are made up of smaller units called amino acids, have unique 3D shapes and drive every action in the human body. They help sperm cells race towards oocytes, regulate foetal growth, digest food, activate the immune system when microbes enter the body and stir memories in the brain, among countless other functions.

“The genome sequence gave us the alphabets of the blueprint for life, but everything in the body is done by proteins,” said Shahid Jameel, the chief executive officer of the Wellcome Trust-DBT India Alliance that also supported the study. “We haven’t had a comprehensive catalogue of all proteins in the body — until now,” Jameel said.

The proteome-mapping effort was driven largely by PhD scholars at the IOB in Bangalore and in Pandey's laboratory at Johns Hopkins and relied on a shoestring budget of about $700,000 (Rs 4.13 crore) with the US National Institutes of Health also funding some components of the study.

The bill for the human genome sequencing effort was, by contrast, $2.7 billion (around Rs 15,900 crore).

“We still need to understand the exact functions of many of these proteins,” said Harsha Gowda, a research scientist at the IOB who was part of the study team. Among the 17,294 proteins catalogued, Gowda said, the functions of roughly half of these proteins remain unknown.

Over the past decade, scientists have used the human genome sequence data to predict the existence of some 3,500 proteins that hadn’t been found so far.

The new study has detected 2535 of these “missing proteins”. One of these is a component of haemoglobin found in red blood cells. “One might imagine that in 2014, we would know all there is to know about haemoglobin, but even this is not true,” said Pandey, a doctor-turned-scientist.

“We’re hoping this proteome map will accelerate efforts to understand better how specific proteins work and what they do — both in normal tissues and diseased tissues,” said Pandey, a doctor-turned-research scientist.

Pandey, the son of an Air Force officer, had studied in Kendriya Vidyalayas in Delhi, Kanpur, Mumbai, and Chennai before studying medicine at the Armed Forces Medical College, Pune, and moving to the US for doctoral research and residency training in pathology.

Another research team led by biochemist Bernhard Kuster in Germany has also independently assembled evidence of proteins for around 18,000 human genes, with a core set of 12,000 proteins expressed in different tissues. A paper describing that effort will also appear in Nature on Thursday.

But the Indian-American study used a novel analysis strategy that, Gowda said, helped the researchers discover the new, previously unknown proteins.

“The 200 novel proteins tell us that there is still a huge part of fundamental biology we don’t understand,” Gowda told this newspaper. “Many proteins appear to evade detection through conventional search strategies.”

Biotechnology secretary VijayRaghavan says the proteome mapping effort has a lesson for science and funding. “This is collaborative science between Bangalore and Baltimore and collaborative funding with many agencies," VijayRaghavan said. “Big barriers in science can collapse when people work together.”

The data sets generated by the Indian-American study and the German study are complementary in some ways and will allow the scientific community to refer to multiple lines of evidence for each protein coming from independent proteome-mapping efforts.

The other co-authors of the Indian-American study are based at the National Institute of Mental Health and Neurosciences, Bangalore, the Post-Graduate Institute of Medical Education and Research, Chandigarh, the Armed Forces Medical College, Pune, and other academic institutions in Canada, Chile, Hong Kong, the UK, and the US.