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Wading through the literature: Using Charisma to explore body fluid based biomarkers in Multiple Sclerosis

by Rick Blevins, PhD, Co-founder and CIO at Virtual-Rx, and Allison Provost, PhD, Scientific Program Manager at Orion Bionetworks

May 21, 2015 at 12pm ET

The progression of multiple sclerosis (MS) is characterized by debilitating relapses that are difficult to predict. Biomarkers that can predict relapses or response to therapeutic intervention could be very helpful in the management of MS. Basic science research has identified a wealth of possible biomarker candidates, but very few have been clinically validated.

In our webinar, we will discuss a new computational tool we are using to evaluate the MS biomarker literature. Charisma is a new cyber-infrastructure which provides facile and normalized access to a wide range of data currently in use in the bioinformatics, genomics and clinical informatics domains (and many others). State of the art big-data, semantic and natural language tools allow the creation of knowledgebases which are self-updating and classically cybernetic.

We propose that computational approaches in the review of basic science literature will aide in the efficient identification of predictive biomarker candidates that may be prime for clinical validation in MS.

About Rick Blevins

Rick Blevins, PhD, has 30 years of pharmaceutical and academic research experience, and is an informatics expert – from chemical informatics through systems biology.  Rick served as the global head of bioinformatics at Merck, the US head of bioinformatics analysis at GSK and the director of cyber-infrastructure development for the NSF funded iPlant project at the University of Arizona Bio5 institute. Rick also designed and developed the infrastructure used at Caris Life Sciences in support of personalized medicine in oncology. Currently, Rick is a co-founder and CIO for Virtual-Rx, a virtual pharmaceutical platform company and president of Bridlewood Consulting.

About Allison Provost

Allison Provost is a Scientific Program Manager at Orion Bionetworks and overseeing Orion’s Initiative on Biomarkers in Neurodegenerative Disease, which seeks to facilitate the development of brain disease diagnostics through translational approaches. She received a Ph.D. in Neuroscience from Harvard University where she was a National Science Foundation Graduate Fellow and Sackler Fellow in Psychobiology. Allison’s dissertation research focused on the role of serotonin in normal brain function and the effects of neuromodulator release on time scales relevant to ongoing behavior. Additionally, she has developed her business skills through coursework at MIT’s Sloan School of Management and Harvard’s Mini-MBA. Allison obtained her BA with honors from UC Berkeley in Molecular and Cell Biology.

Orion Bionetworks is a Cambridge, MA, non-profit 501(c)(3) research organization that builds Bionetwork Alliance communities to assemble and integrate high-dimensional biomarker, biosensor, and phenotypic data and advance knowledge discovery through the power of predictive analytics and computer modeling to accelerate the development of new diagnostics, treatments, and cures for brain disorders.

Orion’s webinar series fosters an exchange of knowledge on the latest breakthroughs in a variety of technical fields including bioinformatics, computational modeling, biomarker research, and nanotechnologies, and discusses how these can be utilized to accelerate time to cure for brain disease. We are inviting expert speakers to submit proposals for future webinars on the above topics. Each webinar is 50 minutes in length, followed by a 10-minute Q&A with questions submitted virtually by the participants. All webinars are free and open to the public.

Click here to register for this webinar.

For any questions and to submit webinar proposals, please contact our colleagues at Percolation Communications (Gloria.Dunn@percolationcom.com).

We thank you in advance for helping to make this a dynamic and informative event.

The post Wading through the literature: Using Charisma to explore body fluid based biomarkers in Multiple Sclerosis appeared first on Orion Bionetworks.

My son’s first seizure happened when he was 14 weeks old. Ben was in the Baby Bjorn on my chest, apparently a peacefully sleeping infant. His eyes opened and rolled back into his head. It only lasted a few seconds. The first time it happened, I had no idea that it was a seizure. It took a few days and multiple, increasingly longer, episodes for me to realize that I should take him to the pediatrician’s office. Ben had a seizure in front of his doctor, who immediately admitted him to the hospital for a video EEG. For the next few weeks, they told us not to worry. Most babies’ seizures are easily treatable with medication. Most babies outgrow their seizures. Almost six years later, Ben is still having daily seizures. They have morphed over the years, getting longer and more severe. For the last two years, his seizures have lasted more than 15 minutes. He stops breathing during the initial tonic phase and turns blue. We keep an oxygen tank by his bed. He bites his lips and tongue which leaves a bloody stain on his pillow. His face grimaces and his little body convulses grotesquely. Almost every day. Even after trials of 12 different anti-seizure drugs. Even after surgical implantation of a vagus nerve stimulator; you can see the round disc through his skin by his left collarbone, its attached wire running under the skin up his neck. Even after resective brain surgery – during which he lost half of his right parietal lobe – and which left a wide scar that leads from just behind his right ear in an arc to the back of his head and up to his forehead.

This disease has devastated me. Unlike my husband, who says I can’t live and die by every seizure, I am in tears after most seizures. They are horrific to witness; it has not gotten easier over the years. Yet, I am grateful. Ben doesn’t have drop attacks. These are a particular type of seizure that can happen at any time, without warning. Children with drop attacks break bones and get concussions. I am grateful that Ben doesn’t experience ictal fear anymore. When he was two years old, he would scream out in absolute terror during a seizure. Now, he goes to sleep right after the seizure and wakes up the next morning, fairly well recovered. I am grateful that Ben is a happy child who lives in the moment. He doesn’t seem to know that he has these awful seizures in his sleep. I am incredibly grateful for that. When Ben was two, I made a choice not to be a suffering mother, to let joy live side by side with grief. It has taken me almost six years, but I do now get glimpses that life can be joyful. This disease has taken a big toll on me and my family, but it hasn’t beaten us.

An estimated 3 million Americans and 65 million people worldwide suffer from epilepsy. Thirty percent of these patients live with uncontrolled seizures. That is, current treatments do not stop seizures from occurring in almost 1 million Americans and 20 million people worldwide. Sudden Unexpected Death in Epilepsy (SUDEP) accounts for 34% of all sudden deaths in children. Epilepsy affects more people than multiples sclerosis, cerebral palsy, muscular dystrophy and Parkinson’s disease combined – yet receives fewer federal dollars per patient than each of these diseases (cureepilepsy.org). I want epilepsy removed from the shadows, talked about openly, and given the amount of attention commensurate with its impact on the population.

Drug development efforts have, unfortunately, failed to address treatment-resistant epilepsy. The percentage of patients living with uncontrolled seizures has not changed over the last 50 years despite the development of ~30 new drugs. There are a few reasons for this: two-thirds of diagnosed epilepsies have no known cause; animal models don’t adequately model human disease; and most of the drugs are not rationally designed – they are blanket drugs that serve to decrease overall excitability in the brain. The problem with that approach is that epilepsy is not one disease. Brain malformations, metabolic disorders, brain trauma, and ion channel mutations are just some of the molecularly very different known etiologies underlying epilepsy. These all likely require distinct treatments. History shows us that traditional hypothesis-driven research cannot adequately address the complexity of this brain disease. Orion Bionetworks engages in a completely different approach to understanding brain disease – hypothesis-generating research that harnesses the power of big data analytics. This approach can both help us understand the natural history of the disease, and identify molecular pathways as drug targets that might otherwise remain undiscovered. I am incredibly optimistic that Orion, through its partnerships and whole brain approach, can make a meaningful difference to people not only living with epilepsy, but all brain disorders that it tackles. In the world of scientific discovery, true collaboration serves the patient best, but is very rare. Orion’s approach depends on collaboration; it openly and freely shares its data to encourage new discoveries.

The post State of Mind – Epilepsy appeared first on Orion Bionetworks.

Gaining Insights in Multiple Sclerosis by Causal Network Analysis

by Dr. Boris Hayete, Senior Director of Genomic Medicine at GNS Healthcare

April 30, 2015 at 12pm ET

Network methods can reveal insights into disease biology and have been successfully applied to a variety of datasets. A particular field of network inference is causal inference, which focuses on inference that differentiates between likely causal and likely reactive relationships among variables, resulting in greater parsimony and biological relevance of the findings. In this webinar, Dr. Hayete will present the application of GNS Healthcare’s proprietary causal inference platform to the Orion MS dataset, discussing both the methodology and the generated findings.

About Dr. Boris Hayete

As Senior Director of Genomic Medicine at GNS Healthcare, Boris Hayete, PhD, leads a scientific team focusing on systems biology and related areas. He has coauthored a number of peer-reviewed articles on systems biology and has developed a widely used network inference algorithm.

Dr. Hayete has more than a decade of experience in network inference and systems biology; he has been at GNS Healthcare for over 7 years and was previously at the Boston University Bioinformatics PhD program. Prior to earning his PhD, Dr. Hayete conducted research and applied work in web search, and he has a bachelor’s degree and master’s degree in computer science with a focus on machine learning and natural language processing from the Johns Hopkins University.

Orion Bionetworks is a Cambridge, MA, non-profit 501(c)(3) research organization that builds Bionetwork Alliance communities to assemble and integrate high-dimensional biomarker, biosensor, and phenotypic data and advance knowledge discovery through the power of predictive analytics and computer modeling to accelerate the development of new diagnostics, treatments, and cures for brain disorders.

Orion’s webinar series fosters an exchange of knowledge on the latest breakthroughs in a variety of technical fields including bioinformatics, computational modeling, biomarker research, and nanotechnologies, and discusses how these can be utilized to accelerate time to cure for brain disease. We are inviting expert speakers to submit proposals for future webinars on the above topics. Each webinar is 50 minutes in length, followed by a 10-minute Q&A with questions submitted virtually by the participants. All webinars are free and open to the public.

Click here to register for this webinar.

For any questions and to submit webinar proposals, please contact our colleagues at Percolation Communications (Gloria.Dunn@percolationcom.com).

We thank you in advance for helping to make this a dynamic and informative event.

The post Gaining Insights in Multiple Sclerosis by Causal Network Analysis appeared first on Orion Bionetworks.

I was first diagnosed with depression when I was 33, right after the birth of my first child.  It was textbook postpartum depression, but there were other previous symptoms that were over looked this time around.  I found a therapist and began sessions and my primary care physician was able to prescribe an antidepressant for me.  I was on the meds for about a week or two and the difference in my behavior and outlook on life was amazing.  I called my doctor and said to him, there’s no need for me to be on this, I feel great, back to my “normal” self.  He kind of chuckled and said that’s great but it was the meds that were helping me and I needed to stay on them for a while longer.  So I took the meds for 6 months and then I was able to go off them.  I stopped my therapy because I was doing great, a new mom with a wonderful new baby and life.  I never gave depression another thought.  Three years later I got pregnant with my second child and this time things were very different…

My first trimester was very normal as it was with my first child but by the second trimester I knew something wasn’t right.  I had these symptoms with my first child but not as severe and this time I knew I needed to get help right away.  I called my therapist, my GP and my obstetrician.  I was diagnosed with Antepartum Depression and again started medication and therapy.  I looked into this condition because I had never heard of it and this is a little of what I discovered: 

All too often, depression is not diagnosed properly during pregnancy because people think it is just another type of hormonal imbalance. This assumption can be dangerous for the mother and the unborn baby.  According to The American Congress of Obstetricians and Gynecologists, between 14-23% of women will struggle with some symptoms of depression in pregnancy.

Depression during pregnancy, or antepartum depression, is a mood disorder just like clinical depression. Mood disorders are biological illnesses that involve changes in brain chemistry. During pregnancy, hormone changes can affect brain chemicals, which are directly related to depression and anxiety.  These can be worsened by difficult life situations, which can result in depression during pregnancy.  Untreated depression can lead to poor nutrition, drinking, smoking, and suicidal behavior, which can then cause premature birth, low birth weight, and developmental problems. Babies born to mothers who are depressed may be less active, show less attention and are more irritable and agitated than babies born to moms who are not depressed. This is why getting the right help is so important for both mom and baby.   (Information taken from http://americanpregnancy.org/pregnancy-health/depression-during-pregnancy/)

As you get older it seems this condition gets more intense and that’s what made me go for help, I just couldn’t get through it this time on my own.  But I did manage to get through everything with a lot of support and in the end I was blessed with another healthy baby, but my symptoms did not go away as quickly as was the case with my first child.  It was much harder to get back to “normal” this time and I was on the medication and going for therapy for over a year.  Then finally the time came where I was better and able to handle life and all its bumps so again I was off the medication but I stayed with my therapy to help me cope when things were difficult.  Well I have been in therapy for a little over 12 years and have been on and off medication for depression several times. 

Yes it has to do with brain chemistry and hormones but depression can also be hereditary, and mine is.  I discovered people in my family who suffered with depression but not many received or looked for help.  Many times self-medication was the answer, and that meant drinking.  I come from a long line of alcoholics as well, these disorders or diseases seem to go hand in hand.  After thinking back, I noticed that I would do the same thing before I had my children.  I had a bad day at work, have a drink.  I was “blue” or upset, have a drink.  Something with me “just didn’t feel right”, have a drink.  The drinking really didn’t help but it made me numb to the problem at hand and for a while I was good and was able to deal with things.  This didn’t happen very often either so I never saw a pattern to it until now looking back. 

I’m 45 now and currently on medication for depression but over the years I developed anxiety as well and that seems to be giving me the most trouble now.  Yes I get blue but it passes fairly quickly.  What is difficult now is dealing with the anxiety and if it gets very bad, the panic attacks that go along with it.  I see that when I am overwhelmed its worse and I need my meds more.  And the bad thing about the medication is, it can make you lethargic/sleepy and you’re not motivated to get things done, or you’re slow to accomplish them, and then get anxious about not doing things on time or at all and I get that feeling again and I’m right back to an attack of anxiety….it’s a vicious cycle.

I’ve learned over the years how to deal with depression and now anxiety but it was not easy.  It affected everything in my life; my self-esteem – I saw myself as ugly, stupid, not worthy of being alive.  My health – I let my eating habits get bad, I have yo-yoed with my weight, I’m still smoking even though I have tried many times to quit, it also effects my family and my children – they see me struggle with bad days, I cry, I get wound up and seem to have so much nervous energy, sometime I snap at them too.  That’s the part I hate the most, but I always apologize after and try to explain why I did what I did or said what I said.  And work was affected as well, not being able to do the work or do it on time, forgetting things, missed days because of a bad day and more.  Depression affects more than the person suffering from it but if you have a good support system, people who understand you and what you are going through, it makes it a lot more bearable and I am so grateful to have so many wonderful people and family members behind me.

Orion Bionetworks is working on finding better treatments and cures for brain disorders like depression and many others.  As I understand it, they are using computer and medical technologies along with biological and gene data, brain function and many other types of information and data to understand, study, explore and piece together these brain diseases/disorders to find better ways of treating and maybe one day curing them.  But until that day comes, I know I have these conditions, but I refuse to let them dictate my entire life, I will overcome the bad days and cherish the good and never stop trying to better myself physically, mentally and emotionally.

The post State of Mind – Living with Depression appeared first on Orion Bionetworks.

ClarifyRA: Getting to Holistic Disease Management for RA Patients

by Dr. Renée Deehan Kenney, Senior Vice President of Research & Development at Selventa

March 11, 2015 at 12pm ET

RA patients are faced with a myriad of therapeutic choices after failure to respond to first line therapies. While this is encouraging, RA is a progressive disease and time spent on the wrong therapy results in irrevocable disease progression. ClarifyRA is an attempt towards providing a holistic diagnostic that not only provides a molecular measure of patient’s disease activity but also information about the likelihood of response to treatment.

About Dr. Renée Deehan Kenney

Dr. Renée Deehan Kenney joined Selventa, a personalized medicine company that specializes in working with large-scale molecular and clinical data in 2006.  As Head of Research, she develops and executes the scientific strategy for Selventa’s internal discovery programs as well as consulting services.  She leverages her understanding of both the industry and client needs to develop custom strategies that translate scientific challenges into navigable solutions that are predicated on her fundamental belief that a comprehensive understanding of the molecular basis of an individual patient’s disease is required for successful target discovery and biomarker development and ultimately for personalized medicine in the clinic.  Dr. Deehan Kenney has led over 50 collaborations with pharmaceutical, consumer product, and academic partners.  Before Selventa, she was earning her Ph.D in molecular and cell biology at the University of California, Berkeley and holds a BSE in engineering from the University of Pennsylvania.

The post ClarifyRA: Getting to Holistic Disease Management for RA Patients appeared first on Orion Bionetworks.

The former head of Johnson & Johnson’s ($JNJ) initiative to develop stratified drugs for Alzheimer’s disease is trying to crowdfund the development of computer simulations of brain disorders. Magali Haas is seeking $299,900 for the project, which builds on a multiple sclerosis prediction model created by her nonprofit, Orion Bionetworks.

Haas began raising the money through crowdfunding site Indiegogo earlier this month. At the time of this writing, the campaign has attracted $5,354. Whatever cash is raised–regardless of whether the campaign falls short of its $299,900 target–will go toward the development of Orion MS 2.0, a scaling-up and expansion of the nonprofit’s first venture into MS modeling. Orion MS 1.0 used cash from J&J’s Janssen and data on 9,000 patients from Brigham and Women’s Hospital, PatientsLikeMe and Accelerated Cure Project to build a computer model of MS.

For version 2.0, Orion Bionetworks wants to gather data using biosensors and other methods from 1,000 people in PatientsLikeMe’s network, while also expanding the array of computational methods it uses to crunch the data. Whatever Orion Bionetworks can raise through Indiegogo is unlikely to fully fund its ambitions, but the organization thinks the cash can help it tap more traditional sources of financing. The plan is to add more members to the alliance, continue writing grant proposals and land a funding partnership.

Read the full article here.

Visit the fundraising campaign here.

The post Orion Crowdfunding Campaign Featured in FierceBiotechIT appeared first on Orion Bionetworks.

by Christina McCarthy

It began with a phone call.  The guidance counselor from our local high school, calling to say my oldest daughter, Madison, was being transported to a local emergency room. As a parent of 4 children, having a child rushed to an emergency room is old hat, but this wasn’t an “I can handle it” typical situation. Madison was being sent to a psychiatric emergency room for immediate evaluation. To say I was stunned is a complete understatement. Madison was a brilliant honor roll student, scoring almost 2000 on her SATs without even studying. She was an amazing actress with lead or secondary rolls in most performances in school. She had scholarships to colleges of her choice by her junior year and was planning her future in every minute detail.  Planning…planning her final days with us because she had made a decision that she was tired. Tired of being the brilliant kid, who was so disorganized she couldn’t find her homework from the night before that she swore she put it away. Tired of always scoring 100+ on her tests but couldn’t organize herself to handle each day therefore her grades begin to suffer to Cs & Ds. Tired of acting like her life was great, when in actuality, she was suffering from severe depression, anxiety, bulimia, mood swings and bipolar disorder – all undiagnosed.  

Madison, my brilliant and amazing unraveled daughter is actually my stepdaughter. She unfortunately was dealt a hand that she had no control over because her biological mother’s line has mental illness that goes back at least three generations with schizophrenia and borderline personality disorder.  Given her family history, her father made a decision to give her as much information as possible so she could be prepared “in case” she ever showed any signs of MI. She was prepared, she already knew that her road was beginning to bend in a direction that she wasn’t going to be able to control but she never spoke up or told us the truth about how she was feeling. 

This day was the beginning of a rollercoaster ride for a family of six.  Madison was transferred to a long-term facility for two weeks, nothing that anyone in our family has ever experienced. There was uncertainty and confusion, especially for her younger sisters and brother. As a parent, who has to remain strong for the rest of your family, you don’t have the luxury to breakdown, to wake up and realize that is wasn’t a really bad dream, and this is now the life that we all will lead into our future. 

The past seven years we have seen two full hospitalizations, two long-term outpatient treatment programs, countless hours of counseling along with years of compliance and non-compliance with medications. As a parent, we have attended numerous psychiatric appointments, parent meetings, self-help classes and read an unimaginable amount of books on mental illness and bi-polar disorder. We participate in the annual NAMI walks to raise awareness and promote removing the stigma that people perceive about mental illness. 

The one thing we do have is Madison, she is alive and as well as she wants to be as an adult. She has come to a decision that she refuses to take any medication because it makes her feel fuzzy and unemotional. She works full-time as a bank teller and currently lives at home with the goal to move out on her own within one year. As a parent, we are supportive in her decision because she is an adult but have strict guidelines within our home so that any emotional changes she does go through, we can protect her younger brother and sisters. Do we agree that she shouldn’t be medicated? No, we believe that every person, adult or child, which is diagnosed with a disorder should be taking medication, provided that quality of life is maintained or improved. We have learned that is it critical that you listen to your children constantly and try to understand how and why they feel the way they do. 

Madison’s future is uncharted and although she would love to start a family one day, she has already made a decision that she doesn’t want to have her own children. She is fearful that she will continue to pass the mental illness to her own children and she “wouldn’t wish that upon her worst enemy.”  She hopes for a future that provides better insight for mental illness patients.  Having a company, like Orion Bionetworks, with their predictive biomarkers research would help people like Madison.  A future in which we could know the probability that someone would become ill and we could be more proactive in an individual’s care. Getting ahead of a mental illness and understanding how to treat it is half the battle, Orion Bionetworks can help to pave the way through that battlefield.  

The post STATE OF MIND: History can’t repeat itself appeared first on Orion Bionetworks.

Mechanism-based CNS Disease Modeling: Applications in Neurology and Psychiatry Drug Research & Development

by Hugo Geerts, PhD, Chief Scientific Officer of In Silico Biosciences, faculty at Perelman School of Medicine (University of Pennsylvania) and Drexel University Department of Pharmacology

February 26, 2015 at 12pm ET

The post Mechanism-based CNS Disease Modeling: Applications in Neurology and Psychiatry Drug Research & Development appeared first on Orion Bionetworks.

For over 20 years, Tri-Conference attendees gained insight and knowledge by attending the event, knowledge that they were able to take with them, and have an immediate impact on their research. Plan to attend this year’s event where you can be part of driving change and working towards shaping the future of medicine. Learn more at TriConference.com.

The post Molecular Medicine Tri-Conference | February 15-20, 2015 | San Francisco, CA appeared first on Orion Bionetworks.