Orion Bionetworks 2015 Annual Conference
Orion Bionetworks hosted their second annual conference at the Broad Institute in Cambridge, MA on June 12, 2015. The day was packed with presentations from leaders in patient advocacy, wearable technologies, neuropsychiatric biomarkers research, and computational modeling of brain diseases.
- Neuropsychiatric illness is an enormous burden worldwide, and faster progress can be made if we unite our research efforts by sharing data, protocols, resources, and knowledge.
- Wearable technologies are becoming more complex, ubiquitous, and useful and when utilized to collect patient data, can lead to key insights into disease as well as patient empowerment.
- Getting to precision medicine for neuropsychiatric disorders requires deeper biological knowledge concerning the heterogeneity of brain disease, and we will only gain this knowledge through well-planned and carefully executed population studies of patients on the “omic” scale.
- Knowledge engineering is the application of bioinformatics tools to help identify what is already known in neuropsychiatric disease within the published domain, across diseases and animal models, and will drive research forward more efficiently. It also creates a space for negative results to be reported.
- Computational modeling of neuropsychiatric diseases can lead to better patient stratification, prediction and refinement of clinical trials, deeper understanding of disease progression, and meaningful insights into the underlying disease biology.
Magali Haas, CEO, founder, and President of Orion Bionetworks, LLC, kicked off the day by outlining the international burden of neuropsychiatric and neurological disorders, noting that an article from the Lancet Article reported that neuropsychiatric disorders rank in the top ten causes of disability in all countries. One in five people will suffer from brain disease in their lifetime and this disease burden costs over a trillion dollars annually. Society is buckling under this immense social and financial burden because of lack of cures, diagnostics, and knowledge of the underlying causes of disease. These are the issues that Orion Bionetworks is seeking to tackle. Dr. Haas presented a strategic overview and a roadmap of Orion’s activities. She provided a compelling case for shifting the paradigm of translational science to one that embraces complexity, i.e. Systems Biology and which reverse- engineers disease from human data via next-generation technologies that measure biosignals and biomarkers. Finally, she described how the multiple sclerosis (MS) 1.0 bionetwork program brought together multi-disciplinary partners from academia, computational & bioinformatics industry, non-profits, and patient-powered networks to create the world’s largest MS biorepository housed in TranSMART and build the first predictive multi-dimensional disease models. Early results of the MS model are promising and there are significant opportunities to extract deeper insights with further study of the models.
The Whole Brain Movement
To discuss large scale, community-based solutions to cure brain disease, a panel entitled “Patient Matters- Busting the Diagnostic Silos” featuring a speech by David Eichenbaum, a political strategist interested in building a social campaign in favor of a “Whole Brain Approach.” He pointed out that 1.4 billion people suffer from brain disease worldwide, a staggering number, yet brain disease research is heavily siloed by disease. Considering the massiveness of the global brain disease problem, Eichenbaum asked citizens, scientists, and patients to work together to break down the barriers for data and resource sharing in neuroscience research. A panel consisting of Heather Snyder, Director of Medical and Scientific Operations at the Alzheimer’s Association, Inez Jabalpurwala, CEO of Brain Canada, Catherine Jacobsen, an epilepsy advocate, and Robert McBurney, CEO of Accelerated Cure Project for MS, and Eichenbaum, discussed the need for engagement and education of government entities, patients, and scientists on the benefits of a united front in the funding and research of brain disorders. Brain disorder socioeconomic burden is greater than diabetes, cardiovascular disease and cancer combined. Many organizations, including the Alzheimer’s Association and Accelerated Cure Project for MS, have gone to great lengths to ensure that researchers who they support share their data and findings openly within the scientific community. Canada has a successful program in which Brain Canada doubles all money to researchers contingent upon data sharing in the Brain Canada database.
Patient Empowerment through Wearable Technologies
Following the “Whole Brain” discussion the conference moved on to personal wearable devices that can empower and engage patients in their own care. Pablo Arce of Ymedia Labs and project lead on the ResearchKit for the Apple Watch delivered the Keynote address about the power and potential of the ResearchKit in brain research. The ResearchKit allows patients to collect individual data via active tasks as well as surveys and share it with researchers through stringent informed consent protocols. After launching in March 2015, they are finding that patients are providing high quality data because the device is helpful to patients and patients can see immediate benefits. Building on the theme of wearable devices, Rudi Cartyvels Sr. Vice President of Imec and Giampaolo Brichetto, Coordinator of Research and Rehabilitation at the Italian Multiple Sclerosis Society, each presented on next generation wearable technologies. Imec is making tremendous advancements in nanotechnology and the use of silicon technologies for diagnostics in brain disease and beyond. From microfluidic chips that can detect single cancer cells to devices that can record from 456 sites in the brain simultaneously, Imec is creating the technologies of tomorrow through collaboration and precompetitive agreements with industry partners. Brichetto presented an initiative by the Italian MS Society to empower MS patients by arming patients with devices to self report their health status and creating decision tools for patients based on their personal status through the DECIDEMS program of which Orion is a partner. The DECIDEMS devices are focused on tracking the progress of neurological symptoms and helping to determine whether therapeutic interventions alleviate symptoms in real time.
Precision Medicine: Where’s the Precision?
In light of the vast quantities of patient data collected by wearable devices and in medical facilities, how close are we to delivering precision medicine that is it tailored to individual patients? In a panel called “Precision Medicine: Where’s the Precision?” Andreas Jeromin of Iron Horse Diagnostics, Sid O’Bryant of Institute for Aging and Alzheimer’s Disease Research, University of North Texas Health Science Center, Diana Perkins of the University of North Carolina, Chapel Hill and the North American Prodrome Longitudinal Study each presented on gaps in medical knowledge that are keeping us from precision medicine. Biomarkers of disease progress are crucial for precision medicine. Jeromin suggested that we must change the business model for advancing a biomarker assay to market. While basic scientists are reporting many new discoveries in brain disorder biomarkers, the infrastructure to validate these biomarkers is extremely poor, so few biomarkers make it past the discovery stage. Therefore, there is a dearth of diagnostics for patients. Perkins pointed out that key barrier to progress is lack of high quality biobanking from longitudinal studies. 1 in 100 people have schizophrenia, and the time to diagnosis and treating patients is long and arduous. A blood biomarker or set of biomarkers to distinguish young people at risk for early intervention would greatly facilitate drug development and treatment. Also understanding the biology behind blood biomarkers, which tend to be markers of inflammation, will lead to a deeper understanding of the inflammation’s role in schizophrenia and other developmental brain diseases. O’Bryant pointed out that we treat the disease rather than the patient. As in schizophrenia, inflammation, in addition to neurodegeneration, plays a major role in Alzheimer’s Disease, and he is finding that a significant percentage of patients respond to treatment with NSAIDS which are widely available drugs. O’Bryant also reported on the first consensus guidelines developed to address standardization of pre-analytic methods in fluid-based biomarker collection.
To find cures and better treatments for brain diseases we must grasp what has already been discovered and build on these results. As mentioned above, much has been reported at the discovery phase, but the majority of it must be validated. Organizing these findings into a knowledgebase that can be used to tackle the problem of converting publications into understanding. Moreover, ideally, one would like to integrate new data with published findings, so creating ecosystems where this is possible is key. Systems biology is meant to work in this complex space, and we, as researchers, must utilize its potential.
Knowledge integration is the main focus of Martin Hoffman-Aptitius from the Fraunhofer Institute for Algorithms and Scientific Computing (SCAI) who presented Aetionomy, a powerful tool that gathers information from the scientific literature in an automated way and translates paper findings into the OpenBel language that can allows for integration of concepts across papers and easy visualization. This knowledge management and knowledge visualization toolkit can be used to deeply understand the existing state of the research across neuroscience disciplines.
Organized and carefully quantified preclinical research, is also a necessity, and while meta-analysis of clinical data has exploded, meta-analysis of preclinical studies is still quite uncommon. SYPHAD (SYstematic neuropsychoPHArmacological Database), presented by Hamid R. Noori of the Central Institute of Mental Health in Mannheim, converges data from more than 30,000 preclinical studies to fill gaps in preclinical knowledge describing the neurochemical effects of psychiatric medications. This is an important step towards robust and repeatable preclinical data and findings which is critically important in bolstering the pipeline for future drugs in brain disease.
Integrating the findings from both clinical and preclinical work has been key to building biophysical models of disease. Hugo Geerts of In Silico Biosciences presented Quantitative Systems Pharmacology (QSP) modeling, a biophysical modeling technique that integrates biophysics, neural network circuits, and clinical outputs and can be used to predict patient drugs responses. These models have successfully projected the outcomes of drug trials in multiple neuropsychiatric conditions, including in Alzheimer’s disease and schizophrenia.
Orion’s Multiple Sclerosis 1.0 Deep Dive
The final part of the day was devoted to presenting Orion’s Multiple Sclerosis (MS) 1.0 project publicly for the first time. Orion used a tour de force of data and modeling talent to model both patient reported data and clinical and bio fluid derived data from the Brigham and Women’s Hospital CLIMB study in MS.
Orion collaborated with PatientsLikeMe (PLM), a social media website for people with chronic illness, to analyze their MS community that consists of over 30,000 patients with provocative results. First, PLM established that their disability scoring system scales with the widely used clinical measures utilized in clinical trials (EDSS), and is therefore, a relevant way to track patient health. Diving into the MS patient reported data showed that relapses are generally characterized by an increase in the number of disabilities rather than the worsening of a single disability. For example, a patient suffering from difficulty controlling hand movements likely will experience a disability in another motor or sensory modality, for example vision, rather than a worsening of hand dexterity. This new finding allows for a deeper understanding evolution of MS in patients.
To better treat MS, we must understand the cellular underpinnings of a relapse. Orion worked with Thomson Reuters to build a pathway driven model on a subset of the CLIMB data (demographic, genomic expression data and clinical outcomes) to identify 56 pathways and 26 subnetworks associated with time to relapse in MS. A k-means clustering analysis identified three distinct stratified patient cohorts whose pathway expression patterns were associated with a high, medium or low risk of relapse. This integration of prior pathway knowledge and patient gene expression data led to more robust models of molecular signatures for patient stratification biomarkers.
To better understand the causal biology of MS, Orion and GNS Healthcare built a data-driven model from CLIMB data, which was presented by Keith Elliston, Consulting Scientific Director at Orion, and Boris Hayete of GNS Healthcare. Using Bayesian inference to go beyond correlations and make causal inferences between data nodes, the Orion MS 1.0 model has uncovered novel genetic drivers of MS as well as new gene expression pathways that may also contribute to disease outcomes. The model is expansive and currently under rigorous study to better understand new drivers of MS. The model has been integrated with a suite of software packages such as Cytoscape, a network visualization software, and NDEX, to allow for big data mining. Additionally, Orion Bionetwork’s partner, Exaptive, a data visualization company, created an interactive interface for the model, allowing users to simulate and interact with the model in real time. Also, to seamlessly cross reference hits from the model with the scientific literature, Orion partner, Virtual Rx, has created an interface with their cybernetic, natural language processing knowledge base, Charisma.
During conference breaks, Orion Alliance Partner, Metacell demonstrated their Gepetto platform. They have created an open data integration and real-time simulation platform.
Finally, we would like to thank the Sponsors of the 2nd Annual Conference, our Silver Sponsors, Biogen and Janssen Pharmaceutica and our Bronze Sponsors, IMEC, Octave Biosciences, PatientsLikeMe, Takeda Pharmaceuticals and Thomson Reuters.