Infectious disease is one of the most formidable problems being faced in the world today. Recent emergence of new pathogens, antibiotic resistant strains of existing pathogens, and re-emergence of diseases thought to be eliminated have pointed out the importance of research to understand infectious diseases. The threat of pandemic from a novel strain of influenza or other viruses is ever present. Understanding the mechanisms of pathogenesis and the complex interplay between host and pathogen is extremely important but in large part has eluded scientific investigation. Pathogens have smaller genomes than their hosts, are present in far larger numbers than their hosts and evolve much more rapidly. Host defense systems are sophisticated and they have the ability to respond to a wide variety of pathogens. The interaction between host and pathogen is complex and involves many iterative responses on both sides in a struggle for survival. New insights into host-pathogen interactions will allow development of novel therapeutic strategies to combat disease.

The development of high-throughput data acquisition methods has prompted an explosion of systems-level data on host-pathogen systems that requires sophisticated and multi-faceted computational modeling approaches to interpret. There is a vast amount of knowledge about pathogens, hosts and their interactions in the form of scientific literature and a myriad of databases. Organization and interpretation of this information can allow a broader understanding of infectious disease processes. The interaction between host and pathogen is nuanced and complicated. Understanding these interactions requires systems biology approaches that aim to elucidate the relationships between components in the system and how these relationships give rise to higher order phenotypes such as pathogenesis.

Addressing these complicated issues requires sophisticated computational modeling approaches that involve statistical and mathematical models, high-throughput data analysis, integration of diverse forms of data, and working closely with the bench biologists, clinicians and epidemiologists who are investigating infectious disease. The community represented at ISMB is perfectly positioned to confront these problems. Our proposed session would highlight key approaches taken by leading investigators to answer crucial questions related to infectious diseases. It would serve to spur discussion in the computational biology community about this important problem.

Part A: Host Response Networks Against Influenza Infections: Virus Attack and Host Defense (2:30 p.m. - 2:55 p.m.)
Speaker Christian Forst, UT Southwestern Medical
Pathogens and host engage in an endless battle trying to out-compete each other. Pathogens (viruses in our case) attempt to hijack host processes for their advantage and for replication, whereas the host tries to defend against such attacks. We have employed two classes of whole-genome siRNA screens to identify (i) host and resistance factors for viral replication, as well as (ii) processes for host cell-survival and death. Together with biochemical network information we were able to identify distinct cellular factors and processes with respect to four distinct phenotypes: (i) resistance factors required for cell survival, (ii) restriction factors inducing cell death, (iii) host factors required for infection, and (iv) host factors that specify death in response to infection. Thus, we are not only able to pin-point processes of the viral life cycle, but also to identify host-defense pathways with diagnostic and therapeutic potential.

Part B: Reconstructing the Regulatory Network of TB: Deconstruction of the Hypoxic Response (3:00 p.m. - 3:25 p.m.)
Speaker: Elham Azizi, Boston University, United States

Part D: Systems Biology of Infectious Disease  (4:00 p.m. - 4:25 p.m.)
Speakers:  Jason McDermott, Pacific Northwest National Laboratory United States
Katrina Waters, Pacific Northwest National Laboratory United States

The study of infectious disease and the complex interplay between pathogens and their hosts has benefitted greatly from the ability to generate many different high-throughput measurements of systems, including transcriptomics, proteomics, and metabolomics. Ways to represent, interpret, and model such multimodal datasets allow improved understanding of the host-pathogen relationship at a systems biology level. We present recent results from systems biology studies of bacterial enteropathogens, Salmonella Typhimurium and Yersinia pestis, as well as respiratory viruses, influenza H5N1 and SARS coronavirus, interacting with their hosts. We will describe the use of network-based approaches to interpretation of high-throughput data and prediction of important components of the system, including experimental validation of some of these predictions. We will also describe how predictive modeling approaches can be used to model important aspects of the interaction and provide predictions of control points for pathogenesis and host response. Finally, we will discuss critical gaps that exist in the systems biology study of infectious diseases and future directions to address those gaps.

The National Centers for Biomedical Computing (NCBC) are cooperative agreement awards that are funded under the NIH Common Fund. The Special Session will highlight the computational scientific achievements of the NCBCs program as well as provide a full palette of software and resources that can be obtained from the individual Centers as accessed through the main portal http://www.ncbcs.org/ There are eight funded Centers that cover biophysical modeling, biomedical ontologies, information integration, tools for gene-phenotype and disease analysis, systems biology, image analysis, and health information modeling and analysis. The centers will create innovative software programs and other tools that enable the biomedical community to integrate, analyze, model, simulate, and share data on human health and disease. Each Center has Cores that are focused on (i) biomedical computational science and (ii) driving biological projects (DBPs) whose intent is to drive the interaction between computational and biomedical computational science. There are numerous efforts in education and training that emanate from the Centers and there is an annual all hands meeting. In addition to the Centers, the NIH and other government agencies have a number of funding announcements that are summarized in the Biomedical Information Science and Technology Initiative (BISTI) Funding Page http://www.bisti.nih.gov/funding/index.asp. The funding page summarizes all initiatives across Government that have a significant component of biomedical computing. This also includes a program for Collaborations with National Centers for Biomedical Computing. The Special Session at ISMB will include three talks from our PIs and a panel that combines representatives from all eight NCBCs and NIH representatives from the Project Team.

Part A:  Biomedical Imaging under the NCBC Program (10:45 a.m. - 11:10 a.m.)
Speakers: Ron Kikinis Brigham and Women's Hospital

A number of the NCBC centers focus on biomedical imaging. In particular, the National Alliance for Medical Image Computing (NA-MIC) researches computational tools for the analysis and visualization of medical image data, the Center for Computational Biology (CCB) is focused on the development of computational biological atlases of different populations, subjects, modalities, and spatio-temporal scales. Several of the other centers have imaging related aims, including IDASH and Simbios Centers.

Part B: Computational Biology and Systems Science under the NCBC Program (11:15 a.m. - 11:40 a.m)
Russ Altman Stanford University, United States