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HUPO Creates New Biomarker Initiatives as Old Initiatives Move Beyond Pilot Phases


MUNICH, Germany — The Human Proteome Organization is creating several new initiatives to help researchers around the world identify proteomic biomarkers for certain diseases, HUPO leaders said here this week during the organization's Fourth Annual World Congress.

The new initiatives, called the HUPO Disease Biomarker Initiatives, will focus initially on cancer and diseases of the central nervous system, kidneys, and cardiovascular system, according to Samir Hanash, chair of HUPO's Initiative Committee.

As part of the initiatives, HUPO will organize research efforts so that scientists can pool resources and develop protocols, standards, and evaluation methods, said HUPO president John Bergeron.

"For any one of these projects, they are far more ambitious than the sequencing of the human genome," said Bergeron, who is also a professor in the department of anatomy and cell biology at McGill University in Montreal. "They are beyond the intellectual and financial resources of any single investigator."

"For any one of these projects, they are far more ambitious than the sequencing of the human genome. They are beyond the intellectual and financial resources of any single investigator."

Rolf Apweiler, the HUPO's new president-elect (see Industry Briefs), added that having an international body would facilitate good discussion between laboratories — something which is essential for large-scale projects.

"With large scale projects, it involves more than just solving a scientific problem. It's much more necessary to have good discussion between labs and to ensure that important results don't get overlooked," said Apweiler, who heads the sequence database group at the European Bioinformatics Institute and chairs HUPO's Proteomics Standards Initiative.

While it is not clear yet who will lead the various disease initiatives, Hanash said that Lee Hartwell of the Fred Hutchinson Cancer Research Center, who won the Nobel Prize in 2001 for his work on uncovering the genetics of cell division, had expressed interest in leading the HUPO cancer initiative.

Bergeron said that under the newly determined management system for the disease initiatives, there would be a built-in rotation of leadership to help bring in additional scientific colleagues.

"We want to balance maximum competition with collaboration," said Bergeron.

HUPO does not provide funding for any of its initiatives, noted Young-Ki Paik, the secretary general of HUPO who is also the director of Korea's Yonsei Proteome Research Center and president of K-HUPO. In order to become official HUPO initiatives, groups must submit proposals to HUPO indicating their sources of funding, resources, and researchers, Paik said.

In order to be considered as an initiative, the group must meet certain standards for being collaborative effort, rather than being based mainly on a single or small group of investigators, Paik added.

As the HUPO Disease Biomarker Initiatives are forming, requests for more tissue-based initiatives and initiatives based on differentially modified proteins continue to grow.

According to Hanash, HUPO has received initiatives requests for research into disease areas for muscles, kidneys, lungs, breasts, prostates, stem cells, urine, saliva, cerebral spinal fluid, nasal mucus, and nipple aspirates, as well as requests for membrane protein, DNA-binding protein, and phosphoprotein initiatives.

A list of criteria for establishing a HUPO initiative will be announced this month, according to the HUPO web site.

Going Beyond Pilot Phases

Meanwhile, a number of established HUPO initiatives are advancing from their pilot phases into their secondary phases. One of the youngest HUPO initiatives, the Human Antibody Initiative, reached a milestone recently by launching the first version of the Human Protein Atlas database, which contains 400,000 immunohistochemistry images created from 718 antibodies (see Proteomics Pioneer).

"In the post-genome era, we have to do high throughput proteomic science."

According to Matthias Uhlén, the chair of the HAI, members of the HAI are validating about 35 antibodies per week. For each antibody, initiative members have about 100 aliquots. They plan to release 50 aliquots to the scientific community as a way of not only sharing, but also further validating the antibodies.

Uhlén said he plans to work systematically through the genome to create an antibody against every protein encoded by a gene. Splice variants are dealt with by aligning all the known variants and attempting to make an antibody that will cover all the variants.

"In the post-genome era, we have to do high throughput proteomic science," said Uhlén. "I will focus on genome-based proteomics and the systematic gene-by-gene analysis of every protein."

He said that in 10 years there will be a collection of antibodies against every human protein.

Within the Human Plasma Proteome Project, the most established HUPO initiative, researchers debated whether the second phase of the initiative should involve disease research (see story). Though some members of the HPPP objected to the initiative becoming involved in clinical studies, Gil Omenn, the chair of the HPPP, said that the initiative would conduct some disease-related studies and contribute to the forming of the HUPO Disease Biomarker Initiatives.

Omenn encouraged members of the scientific community to reanalyze the HPPP pilot data, which is now freely available from the EBI's PRIDE database, the University of Michigan database, and the Institute of Systems Biology's PeptideAtlas database.

Omenn said that the next phase of the HPPP would involve continuing to define standard operation protocols and doing reproducibility studies. In addition, the HPPP plans to put together a list of priority plasma proteins to submit to the HAI for antibody production.

On a deeper level, the HPPP would move on to analyze subproteomes, such as glycoproteins, phosphoproteins, proteotypic peptides, and low molecular weight proteins and peptides within the plasma proteome, Omenn said.

On the liver front, researchers involved with the Human Liver Proteome Project have collected about 100 pieces of liver from French subjects and distributed them among eight reference laboratories. In addition, they have collected about 73 pieces of liver from Chinese subjects and distributed them among seven reference labs.

MS/MS data from the liver analysis are being stored in EBI's PRIDE database.

On the brain front, preliminary analysis of brains from differentially aged mice (see ProteoMonitor 8/5/2005) showed 99 differentially detected spots between adult and juvenile mice; 184 differentially detected spots between adult and fetal mice; and 85 differentially detected spots between juvenile and fetal mice.

A jamboree for the analysis of data collected by researchers involved in the Human Brain Proteome Project is being planned for January 2006 at EBI's headquarters in Hinxton, UK.

— Tien Shun Lee ([email protected])

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