Nov 14 2014

A Symposium to Remember

by at 5:16 pm

With vibrant talks and over 300 attendees from academia, industry and government, the 3rd Annual Biomedical Informatics Symposium at Georgetown was a great place to be on October 2, 2014. I hope many of you had the opportunity to take part and soak in the advances presented from multiple facets of Big Data in biomedical research. If not, you can access the talks, photos and the program here.  Below is a quick recap of the symposium as I witnessed it.

Stanford professor and biotech entrepreneur Atul Butte (@atulbutte) opened his keynote lecture by reminding us of the data deluge at the epicenter of the next scientific revolution. He described four scientific paradigms spanning the centuries as: 1) “Theory” – where people in ancient Greece and China explained their observations of the world around them through natural laws; 2) “Experimentation” – by the 17th century scientists like Newton had begun to devise hypotheses and test them through experimentation; 3) Computation & simulation – The later half of the 20th century witnessed the advent of supercomputers that allowed scientists to explore areas inaccessible to theory or experimentation such as galaxy formation and climate; leading up to the current new paradigm shift in the scientific process; and 4) “Data mining” –exploring relationships among enormous amounts of data to generate and test hypotheses. He illustrated the tremendous benefit of mining public data, such as mining gene expression data from EBI ArrayXpress and NCBI GEO, to discover and develop molecular diagnostics for transplant rejection and preeclampsia.

Did you know that the price to bring a drug to market in the US would pay for 371 Super Bowl ads? With patent cliffs for blockbuster drugs such as Plavix and Lipitor and $290 B in sales risk, Pharma turn to new innovation models such as academic partnering and drug repurposing. In this context, Atul discussed his lab’s work published in Science Translational Medicine using computational repositioning to discover an anti-seizure drug effective against inflammatory bowel disease. He concluded by encouraging participants to take a creative approach to funding science, and treat it as a continuum supported by federal agencies and private organizations. He provided numerous examples of startups originating through ARRA or NIH pilot funding and who have successfully launched companies with robust VC funding to continue development and marketing.

Professor of Oncology and Deputy Director of Lombardi, Mike Atkins, organized and facilitated a panel titled “Cancer Immunotherapies – what can we learn from emerging data?”  Panelist Jim Mule, EVP at Moffitt Cancer Center described ORIEN, the Oncology Research Information Exchange Network between Moffitt and The James Ohio State cancer centers, enabling big data integration and sharing for cancer research and care. As of May 2014, the network assembled data on 443,000 patients. He described a powerful example of precision medicine projects enabled by the network including a 12 chemokine gene expression signatures that predict overall survival in stage IV melanoma patients.

Yvonne Saenger, Director of Melanoma Immunotherapy at Columbia University, discussed a 53 immune-gene panel that is predictive of non-progression in melanoma with resectable stage I, II disease. She and her colleagues used NanoString technology to study transcriptomics with extensive bioinformatics involving literature mining to select genes for the NanoString assay as well as Bayesian approaches to identify key modulatory pathways.

Kate Nathanson, cancer geneticist from Penn, presented the role of inherited (germline) variations in determining drug response to ipilimumab, a monoclonal antibody recently approved by the FDA for treatment of Melanoma and works to activate the immune system by targeting Cytotoxic T Lymphocyte Associated protein (CTLA4). This work provided a nice complement to the somatic studies presented by others on the panel.

Industry perspective was brought to the panel when Julie Gil from Adaptive Biotechnologies discussed the ImmunoSequencing platform tailored to T-Cell and B-Cell receptors for generating diagnostic applications in Oncology.

The recent approval of novel mechanism-based cancer immunotherapies, ipilimumab (Yervoy) and sipuleucel-T (Provenge) has motivated further investigation into the role of immunity in tumor pathogenesis. Despite the recent successes, the field of immunotherapy has experienced nearly a dozen failures in Phase 3. Three major issues need to be addressed to reduce the high failure rates: 1) Finding specific signatures in the tumor microenvironment associated with, or necessary for, response to therapy; 2) Determining molecular mechanisms employed by malignancies to defeat immune recognition and destruction – are they related to specific mutations, pathways, clonal signatures, or organs of origin?; and 3) Identifying a ‘non-inflamed’ tumor that evades the immune system, and then making it ‘inflamed’ for effective immunotherapy treatment. As noted by Kate Nathanson and Robert Vonderheide in Nature Medicine, despite the existing biological and technical hurdles, a framework to implement personalized cancer vaccines in the clinic may be worth considering. The cancer immunotherapies panel at the ICBI symposium shed some new light in this novel direction.

The afternoon panel was kicked-off by UChicago/Argonne National Labs Professor of Computer Science, Ian Foster (@ianfoster), who described the Globus Genomics cloud-based big data analysis platform to accelerate discovery without requiring every lab generating data to acquire a “haystack–sorting” machine to find that proverbial needle. He described projects ranging from 75 to 200 exomes that were analyzed in less than 6 days using a few hundred thousand core compute hours.

As a complement to the infrastructure discussion by Ian, Ben Langmead from Johns Hopkins (@BenLangmead) highlighted tools he and his colleagues developed for RNASeq analysis (Myrna) and multi-experiment gene counts (ReCount). These tools were applied to HapMap and GEUVADIS (Genetic European Variation in Health and Disease) datasets resulting in high profile Nature publications: Understanding mechanisms underlying human gene expression variation with RNA sequencing and Transcriptome and genome sequencing uncovers functional variation in humans. Corporate presentations included Amazon’s Angel Pizarro working with sensitive genomic data on the Amazon cloud, and Qiagen-Ingenuity Systems’ Kate Wendelsdorf’s presentation on assays and informatics tools to study mechanisms of metastases.

A “reality check” special session entitled “Finding Value in Cancer Care” was delivered by Ruesch Center director, John Marshall, who illustrated how the interests of different stakeholders (patients, Pharma, regulatory agencies, and payers) need to be balanced in applying the best and most cost-efficient cancer care.

The event culminated with a reception and poster session with hors devours and wine but not before best poster awards for G-DOC Plus (3rd place), medical literature based clinical decision support (2nd place) and the iPAD award winning first prize to Lombardi’s Luciane Cavalli and her team for “Targeting triple negative breast cancer in African-American Women.”

The free and open-invitation event was made possible by generous support from Lombardi Cancer Center, Georgetown-Howard Universities CTSA, Center for excellence in regulatory science and Georgetown center for cancer systems biology as well as our corporate sponsors.

As I prepare to take off for the annual cancer center informatics directors’ conference in Sonoma, CA (yes more wine coming my way), I am rejuvenated by the vibrant exchanges at the Symposium that promise exciting days ahead for data scientists and bioinformaticians to make impactful contributions to biomedical research.  Let’s continue the conversation – contact me at subha.madhavan@georgetown.edu or find me on Twitter @subhamadhavan

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