Track B report by Dr. John McKinnon
1. Introduction by Francis Collins
Review: As costs for human genome sequencing decrease that application of genomics have continued to expand. In the HIV field, identification of CCR5 delta 32 has been associated for resistance of HIV infection and development of therapeutic agents as Maraviroc. Genomics have also been applied to ART toxicity risk such as the HLA B*5701 allele for ABC hypersensitivity. The field is involved in several areas of HIV research including vaccine development, co-infection , cancer in HIV and other areas
2. Systems biology: when it will deliver for the clinician?, by Sumit Chanda
Review: Next generation sequencing technologies are expected to enhance our understanding of HIV pathogenesis and aid in several areas such as novel therapeutic targets, clearance of viral researvoirs, impact of host genetic variants on disease progression, host immune responses and possible personalization of treatment strategies.
3. Innate immunity: implications for viral control, by Frederic Bushman
Review: Using System Biology approaches several innate immune factors have been recognized such as APOBECs, Trim 5α, Tetherin/BST2 and the newest factor SAMHDI. New research priorities directed at HVI prevention, treatment and cure research will lead the field of research in innate immunity. Crowdsourcing discovery with gene overlapper is a new web tool to help in the study of this genome wide datasets.
4. Genomics: coming to a clinical theater near you, by Philip Tarr
Review: Increasing genomic research is starting to impact clinical care such as HLA B*5701 for abacavir hypersensitivity; understanding genetic determinants of drug levels (ATV, EFV) and toxicities (UGT1A1 with ATV hyperbilirubinemia); inform more complex situations such HIV and co-infections, treatment success for HCV co-infected and better understanding of complex metabolic and aging related conditions such as diabetes and coronary artery disease.
5. HLAB57 does not fully explain the ability of HIV controllers to spontaneously clear Hepatitis C virus (HCV) infection, by Alice Asher
Conclusion: HIV controllers’ patients from the SCOPE cohort were more likely to clear HCV infection than non-controllers. Enrichment of HLA B57 alleles did not explain spontaneous clearance HCV infection in HIV controllers, suggesting that other host factors may be relevant.
Action: Continued evaluation of genomic predictors of HIV control and HCV clearance will further elucidate the immune mechanisms related to successful host immune system disease control.
Track A report by Jacques Fellay
To start the genomics session, Francis Collins shared his thoughts on the future of genomics in HIV medicine. Knowledge of human genetic variation has already has already been successfully applied in the HIV field, most notably in pharmacogenetics. From the resistance phenotype conferred by CCR5 Δ32, a drug has been created, a patient has been cured, and gene therapy is being developed. Emerging large-scale technologies will accelerate the use of genomic tools to address challenges in HIV vaccine development, and in many other areas of HIV research.
Sumit Chandra then presented a global overview of systems biology approaches to HIV. To take advantage of the current proliferation of “omics” technologies, it is necessary to figure out how they interact, to use mathematical modeling to understand how the pieces fit together and to detect emerging properties. The idea is thus to combine the multiple genome-wide studies performed in recent years in HIV in order to create a big HIV-host interaction network, and then to go from static models to prediction of disease outcome. Derived approaches can be used for systems vaccinology (prediction of immunological signatures, testing, modeling, and iterative improvement of vaccine design).
Fred Bushman described a systems approach to innate immune defense against HIV, starting with a description of known HIV restriction factors (APOBECs, TRIM5, BST2 and SAMHD1), and presenting then his plan to uncover additional factors, by combining information on HIV-host protein interaction and on genome-wide siRNA screens. He finished with an invitation to play with the enormous amount of data that is being generated – crowdsourcing discovery: http://microb32.med.upenn.edu/.
Finally, Philip Tarr gave a clinician perspective on HIV genomics: he described a few well-established pharmacogenetic markers, before providing into a more global assessment of the potential of genomics to predict non-HIV-related complications like diabetes and coronary artery disease. Genomic technology, and in particular sequencing, holds enormous potential for researchers, clinicians and patients, even if challenges are considerable.