Clinical OMICS

MAY-JUN 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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www.clinicalomics.com May/June 2017 Clinical OMICs 31 uals, said Wayne C. Koff, Ph.D., presi- dent and CEO of the Human Vaccines Project. "This will help us understand how the immune system works in healthy people, so we can compare it to the compromised immune systems orfin- dividuals with specific diseases," Dr. Koff said. "By looking at immune-me- diated diseases, such as diabetes or inflammatory bowel disease [IBD], and potentially even Alzheimer 's, we can see if there are signatures— biomarkers that will identify these huge diseases earlier than our current tools, and ultimately provide the basis for new diagnostics, vaccines and therapies." For the first three patients, Dr. Crowe said, "we spent probably $200,000 per person just doing the sequencing. It's a little hard to project the final cost of doing 1,000 people, because it's an evolving scenario. But we estimate the total costs will be somewhere between $100 million to $200 million." Dr. Koff has estimated the program costs may decrease as sequencing costs have fallen. Illumina has projected its NovaSeq sequencers, announced in January, will enable a $100 genome. The top-of-the-line NovaSeq 6000, which began shipping during the first quarter, offers an output range of up to 6 Tb, and up to 20 billion reads per run. The Program most likely will use NovaSeqs to sequence the T cell reper- toire, Dr. Crowe said, while relying on Illumina's HiSeq 2500 sequencer for sequencing the B cell repertoire, which will require a system capable of longer reads. The HiSeq 2500 offers an output range of 9 Gb to 1 Tb, and from 300 million up to 4 billion reads per run. "Successfully defining the human immunome will provide the founda- tional knowledge to usher in a new era of vaccine, diagnostic and thera- peutic development," Gary Schroth, Ph.D., distinguished scientist and VP of product development at Illumina, said in a statement. Also supporting the Human Immu- nome Program is an analysis of its datasets through the Human Vaccines Project Bioinformatics and Data Man- agement Core, located at the J. Craig Venter Institute, and the San Diego SuperComputer Center at the Uni- versity of California, San Diego. The Human Immunome Program is one of two key initiatives of the Human Vac- cines Project. The other is the Rules of Immunogenicity Program, which seeks to define the rules of immuno- logical protection. Among key questions the Human Immunome Program expects to address: Just how vast and complex is the immunome? The number of B-cell and T-cell receptors has been estimated as large as 1014, up to 1018 when mutations are figured in. "Our hypothesis is that the vast majority of antibody sequences that could be used are not used," Dr. Crowe said, due to autoimmunity and the fact some sequences just don't fold correctly. "We are hypothesizing that probably less than 1 one-millionth of a potential repertoire actually exists." That hypothesis may prove correct, he added, since the first three partici- pants showed B and T cell repertoires to be remarkably smaller than the potential number. "We want to understand better what's missing, and why is it miss- ing," Dr. Crowe added. "Or, you could turn that around and say, 'What sur- vives this stringent selection, and why is it allowed to survive?'" Researchers hope the program will reveal specific components of the immune system and how it prevents and controls disease. Vanderbilt Vaccine Center

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