Having missed the bus in the blockbuster international Human Genome Project, Indian scientists have now made up by leading a global project to map its protein equivalent -- the Human Proteome Map. The map, an initial catalog of all of the proteins in the human body, has also identified 193 novel proteins from regions of the genome not predicted to code for proteins so far1.
“We missed being involved in the Human Genome Project, so it’s really exciting to have played a significant role in putting together the Human Proteome Map,” says Harsha Gowda of the Institute of Bioinformatics (IOB) in Bangalore, who co-led the project with Akhilesh Pandey, founder director of the institute now at The Johns Hopkins University, USA.
The scientists used 30 different human tissues to identify proteins encoded by 17,294 genes, which is about 84 percent of all of the genes in the human genome predicted to encode proteins.
Gowda, a Wellcome Trust-DBT India Alliance Fellow at IOB, says this is the largest proteome dataset described till date.
In another study published simultaneously2, Bernard Kuster from Technische Universität München, Germany and colleagues have assembled protein evidence for around 18,000 human genes, including a core of 10,000–12,000 proteins expressed in several different tissues. They also identified protein markers that may predict an individual’s resistance or sensitivity to drugs.
Pseudogenes no more
The human genome was successfully sequenced in 2003. Ever since, scientists have strived to determine all the protein-coding genes in the human genome. Estimates of the number of protein coding genes in the human genome relied on indirect methods since studying proteins directly is far more technically challenging than studying genes.
Using cutting edge technologies in protein measurement, the international team has now identified a majority of human genetic protein. The mammoth two-year effort that resulted in massive amounts of data, has thrown up some unexpected results.
For one, a class of genes earlier described as ‘pseudogenes’ for being 'non-functional', have been found to to be coding for proteins after all. “We can’t call them pseudogenes or non-coding RNAs anymore since we now have experimental evidence that they do code for some proteins,” Gowda says. The map will put the spotlight on these new players in the genetic potpourri. “Some bits of our textbooks will perhaps have to be rewritten,” he adds.
The comprehensive human protein dataset will make it easier for other researchers to identify the proteins in their experiments, Pandey says. “We believe our data will become the gold standard in the field, especially because they were all generated using uniform methods and analysis, and state-of-the-art machines,” he said in a Johns Hopkins release.
Spotlight on India
Besides IOB, the Indian contingent in the proteome mapping project comprises about 40 scientists and researchers from the Postgraduate Institute of Medical Education and Research, Chandigarh; Armed Forces Medical College, Pune and National Institute of Mental Health and Neurosciences, Bangalore.
Gowda says the mapping project also marks a significant step in India’s international presence in the ‘omics’ arena. “Until now, the ‘omic’ sciences were not believed to be India’s strong point in the international community. This project, drawing from so many different Indian institutions, proves that with the right infrastructure and knowhow, world class science is possible.”
Shahid Jameel, eminent virologist and CEO of The Wellcome Trust/DBT India Alliance, which part-funded the mapping project, says the Human Genome Project led to deciphering the alphabet of life but how that translates into action and diversity remains to be established. “The Human Proteome Map is a major step in that direction.”
Jameel says while this is an international effort, a majority of the authors work at institutions in India. "This pan-India effort puts India firmly on the global ‘omics’ map.”
Till now the researchers have mapped normal body tissues. They now plan to build on this and look at other organs and tissues. “We are also looking at tissues in pathological conditions such as neurological disorders and various types of cancers to find marker proteins that could help diagnose or treat these disorders,” Gowda says.
1. Kim, M. S. et al. A draft map of the human proteome. Nature 582 (2014) doi: 10.1038/nature13302
2. Wilhelm, M. et al. Mass-spectrometry-based draft of the human proteome. Nature 582 (2014) doi: 10.1038/nature13319