Transplantomics 2012: La Jolla Conference Report
The third "Transplantomics" meeting on functional genomics, genetics, proteomics, microbiomics and biomarker discoveries in transplantation.
Jeremy Chapman, TTS Immediate Past President
and Daniel R. Salomon, Chair
Held in La Jolla, California on March 8-10, 2012 and hosted by TTS and Program Chair Daniel Salomon of The Scripps Research Institute, the Transplantomics conference opened with the challenges confronting transplantation that "omics" may resolve: better understanding of the mechanisms of chronic graft loss, and minimally invasive biomarkers to personalize immunosuppressive therapy and predicted outcomes. Five "state of the art" lectures covered biopsy expression profiling (Philip Halloran), peripheral blood gene expression for acute rejection in kidney and heart transplantation (Bruce McManus), quantitative PCR profiling of urine in kidney transplants (Manikkam Suthanthiran), profiling tolerance in liver and kidney transplants (Alberto Sanchez-Fueyo) and advancing our understanding of chronic allograft injury (Mark Stegall).
The second day provided sessions on genetics, proteomics, epigenetics and microbiomics, and finally, molecular HLA typing and metabolomics. The complexities of genome-wide association studies (GWAS) to correlate individual single-nucleotide polymorphism (SNP) variations to chronic kidney transplant rejection were apparent and despite several thousand patient samples it is clear that GWAS will be valuable, but may not provide the level of genetic insight originally anticipated. Pharmacogenetics and exome-wide sequencing of patients with chronic rejection were considered. Exome sequencing provides single base detail for the protein coding sequences of the entire human genome in each individual—it was interesting to hear whole genome sequencing including the other 99% of the human genome whose function is not entirely clear.
A fascinating paired discussion of the cutting edges of the Proteome field was held that involved either starting with peptides (bottom-up) or proteins (top-down) and in the end constructing complementary pictures of proteins and the critical modifications that determine functions. The Human Proteome Project was described as designed to determine the proteomics of every known human gene. Finally, a novel approach to quantitative proteomics using multi-parameter flow cytometry was described, allowing a whole new approach to clinical diagnostics for transplant rejection and immunosuppression monitoring.
Dan Salomon described strategies developed to profile the immune-epigenomics of naïve and memory T cells at the level of methylating individual CpG sequences in gene promoter regions, while John Iacomini reviewed the master regulatory functions of small noncoding RNAs (microRNAs), emphasizing how epigenetics modifies the flow of information from the fixed sequences of genomic DNA, adding a complex layer of cell regulation. Microbiomics opened a discussion of the way microbes are synergistically associated with human beings and involved in health and disease beyond antibiotic associated diarrhea.
Henry Erlich reviewed an entirely new layer of genetic complexity revealed by molecular HLA typing using deep DNA sequencing. Metabolomics of plasma and urine were presented as methods to develop diagnostic signatures for transplant rejection, tissue injury and function and the Human Metabolome Project was highlighted—the "GenBank of metabolomics." Bioinformatics approaches were elucidated for network mapping using Cytoscape and for making sense of DNA sequencing at the whole exome and whole genome levels. Latest advances in high resolution digital imaging of biopsy histology to create objective and quantitative metrics for transplant pathology showed how we may expect to read and interpret histology in the future.
Allan Kirk described how the immune response evolves from childhood to old age and related this to the challenges of immune-senescence in transplantation. Dan Salomon proposed an integrated view of inflammation as a central driving mechanism of health and disease. We concluded by trying to understand the "value proposition" of diagnostic and predictive biomarkers for clinical transplantation—the next generation of clinical studies of biomarkers and drug therapies must integrate the new discipline of patient-centered, outcomes-based research before we may anticipate persuading anyone to pay.
The 4th International Transplantomics Conference will be held in Cambridge, England in April 2013. Put it in your diary now! Change in our field will be driven by the evolution and application of new technologies—we are just at the beginning.