The Coast to Coast Seminar is an hour-long presentation given on a scientific topic and made accessible to audiences at a number of remote sites through collaboration technology. C2C seminars are held every two weeks throughout the academic year alternating between the West Coast and the East Coast of Canada.
The topic of the Fall 2014 C2C seminar series is "Deep Sequencing Antibody and T-cell Receptor Repertoires for the Study of Infectious and Autoimmune Disease, and Development of Vaccines and Therapeutics".
This Fall 2014 Coast to Coast Seminar Series will examine an immediate and pressing “Big Data” problem faced by researchers examining the immune response to infectious and autoimmune diseases, and those developing vaccines and therapeutic antibodies. The series is partly motivated by a specific middleware prototype that The IRMACS Centre is developing called iReceptor, supported by a CANARIE contract. More importantly, the proposed series will be an important opportunity to help integrate the Canadian and greater international community that is grappling with this Big Data problem.
Only a few years ago, a researcher attempting to characterize the human immune response would have been able to sequence only a few hundred Antibody/B-cell receptor or T-cell receptor sequences per patient. This sequencing might have been conducted as part of research on infectious (e.g., flu, HIV) or autoimmune diseases (e.g., Multiple Sclerosis, Type 1 Diabetes), or during the development of vaccines or therapeutic antibodies. However, with the application of “deep sequencing” or “next generation sequencing” (NGS) techniques, it is now possible to sequence millions of these sequences per individual, per time point (e.g., early or late in infection, before or after vaccination), and from different sets of cells within the body. This is a prime example of the challenge of “Big Data.” In order to optimize the utility of these data for biomedical research and patient care, it will be critical to store, share and compare these huge databases. At present there is no integrated system to easily conduct these comparisons. Such a system will have to present a common data format, for both the sequence data and the sample metadata such as ethnicity, genetic background, treatment regime, gene expression, and clinical outcome, to highlight just some of the supporting data. The ability to share and compare these data is critical to using them optimally for biomedical research and patient care, and will involve significant hurdles in terms of ethics and consent, confidentiality and data security, intellectual property. This is the purpose of the workshops that are being organized in Vancouver, and a Coast to Coast seminar series addressing this topic will help to integrate the Canadian and greater international community as one step in this initiative.
Please contact us at email@example.com if you want to attend one of these seminars.
The first lecture in the series will be broadcast on September 30, 2014
Details can be found at http://www.irmacs.sfu.ca/events/coast-coast-seminars.
Dr George Georgiou, Institute for Cell and Molecular Biology, University of Texas, Austin
Antibodies comprise the effector arm of humoral immunity in humans and thus play a central and essential role in protection against disease. It is straightforward to detect whether an individual has developed a (polyclonal) antibody response to a pathogen or disease agent. However, until now, more than 100 years since the discovery of antibodies, it had not been possible to determine the identities, relative concentrations and functional characteristics of the individual antibodies that comprise the polyclonal response in serum and secretions.
We recently developed a suite of: (i) proteomic, (ii) informatic, (iii) single cell sequencing and (iv) high throughput protein structure-function analysis technologies that has now enabled the deconvolution of the polyclonal antibody pool in biological fluids. These technologies are helping delineate the relationships between steady state antibody production (serological memory) and B cell stimulation/differentiation processes in human health and disease. Novel insights on how vaccines (e.g. tetanus, seasonal flu etc) induce long term protection against pathogen challenge will be discussed.
Dr. George Georgiou is a Cockrell Family Regents Chair in Engineering #9 at the University of Texas, Austin. He is also the head of the Laboratory of Protein Therapeutics and Applied Immunology, which since 2009 has been focused on the discovery and development of protein therapeutics and on the analysis of adaptive immune responses. Dr. Georgiou's current projects include Engineering and preclinical/clinical development of human enzyme therapeutics for the treatment of solid tumors and leukemias; Development of methods for the molecular-level identification of the human antibody repertoire in blood and in secretions, and Analysis of the antibody repertoire elicited by viral infection (e.g. HIV-1) and vaccination to aid the development of more efficient vaccination strategies, among others. Earlier work by the Georgiou lab focused on redox homeostasis and protein biogenesis in bacteria and on the development of platform technologies for protein expression and engineering. These studies led to a number of mechanistic advances that are being used commercially for therapeutic protein manufacturing and protein engineering.
Jacob Glanville, Chief Science Officer, Distributed Bio, Seattle
In the past five years, high throughput immune repertoire sequencing has gone from a novel technique to a ubiquitous assay in immunology, bioengineering and diagnostics discovery. Although the method has given rise to numerous companies and has become increasingly commoditized, its users continue to grapple with the challenge of identifying best applications, best analytical practices, and creating models that fruitfully capture the fundamental diversity structure of the data under investigation. In this seminar I'll introduce our mission of commoditizing routine interpretation of complex repertoire datasets, and review some of what we consider to be the most and least productive uses of repertoire sequencing that have emerged.
Jacob Glanville did his undergraduate studies in Molecular and Cell Biology at UC Berkeley, with an emphasis in Genetics, Genomics and Development. He performed research in two academic laboratories that specialized in quantitative biology. In Dr. Glenys Thomson's HLA Population Genetics laboratory, Jacob designed HLA allele drift simulators, and developed equivalency metrics across HLA typing protocols of various resolutions. In Dr. Sjolander's Berkeley Phylogenomics Group, Jacob published an automated webserver pipeline for phylogenomic functional analysis of proteins. In March 2008, Jacob was recruited to become Principal Scientist at Pfizer's Rinat research facility, where he developed novel computational immunology methods for characterizing and optimizing functions of the adaptive immune system. His published research emphasizes the sequence, structure and functional analysis of antibody repertoires for characterizing genetic variation in patient populations, optimizing phage display libraries based on profiles of natural selection, and engineering monoclonal antibody biologic medicines. Jacob joined as the Scientific Director of Distributed Bio in April 2012.
Dr Andrew Bradbury, Group Leader, Advanced Measurement Science, Los Alamos National Laboratory
Dr. Andrew Bradbury was trained in medicine at the universities of Oxford and London, and subsequently practiced medicine for five years in the UK. He received his Ph.D. (Cambridge University) in the MRC Laboratory of Molecular Biology under the guidance of Dr. Cesar Milstein. After his Ph.D. he spent ten years in Italy: three years as a post doc in the CNR Institute of neurobiology, Rome, Italy; and seven years in Trieste, where he was first visiting professor, and subsequently tenured as assistant professor at the International School for Advanced Studies (SISSA, Trieste, Italy). He has been a staff member at Los Alamos National Lab since July 1999.
He has worked in the field of phage display and antibody engineering for fifteen years, and has helped organize over thirty international congresses and practical courses in this field, both in Europe and the US. He has published over eighty peer reviewed articles, including a number of reviews and commentaries on phage display and antibody engineering, and has 12 filed patents/invention disclosures. He is one of the founder members of “The Antibody Society”, and is on the editorial board of three journals.
Dr. Bradbury's research interests include the application of phage antibody display methods to the study and treatment of human disease and the development of affinity reagents based on fluorescent proteins which he believes will become the affinity reagents of choice for high throughput biology.
Dr. Bradbury's research is funded in part by the New Mexico Spatiotemporal Modeling Center, one of the NIGMS-funded National Centers for Systems Biology.
Dr. Lindsay Cowell, Associate Professor, Department of Clinical Science, UT Southwestern Medical Center, Dallas, Texas
VDJServer is a freely available infrastructure enabling users to leverage national and international cyberinfrastructure for managing, sharing, archiving, and analyzing immune repertoire sequence data. We are collaboratively developing standards for data sharing and software interoperability. Part of these standards are implemented in the mark-up language VDJML. These tools developed in our lab enable the creation of analysis pipelines that can be reused and shared to support scientific reproducibility.
HPCVL offers access to the ADF computational chemistry package. This includes the Amsterdam Density Functional (ADF) code for molecular DFT, as well as the BAND solid-state software, and other components. The software runs on our main M9000 comp[ute cluster. To use this software, please type or include in your setup files the command:
Alternatively, you can type
and will be set up for the most current version. If you need to continue to use earlier versions, you can do so by typing
use adf2008.01 or
Details about using ADF on our systems can be found in the FAQ file.
Please let us know if you encounter any problems with the new version or need assistance running ADF jobs.
Apart from a substantial increase in available disk space, some other alteration have been made to our systems:
Note, that if a specific cluster is desired (for instance, if you have compiled code specifically for the M9000 servers) it can be requested by inserting a line:
#$ -l qname=x.q
into the Grid Engine script, where x.q is 25k.q for the Sunfires and m9k.q is for the M9000's.
HPCVL provides resources to many researchers external to the four CFI applicant institutions. The graph below shows external usage of the CFI funded CPU cluster at the central site. The Canada Foundation for Innovation (CFI),the Ontario Innovation Trust (OIT), and the Ontario Ministry of Research and Innovation have funded the resources at that site and the usage is represented as the percent of the usage of that equipment. Currently, 40 CPUs of the 1008 CPU cores Sun Fire cluster are set aside as workup and test resources and are not included in the percent usage of the cluster.
The total number of installed CPUs in the Sun Fire cluster is 1008 with the additional CPUs being funded through the Sun Microsystems. The total disk storage capacity is 160 TB of T3 StorEdge.