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Big Data From Alzheimer’s Disease Whole Genome Sequencing Will Be Available to Researchers Due to Novel Global Research Database

The Alzheimer’s Association and the Brin Wojcicki Foundation announced recently that massive amounts of new data have been generated by the first “Big Data” project for Alzheimer’s disease. The data will be made freely available to researchers worldwide to quickly advance Alzheimer’s science.

Discussed recently at the Alzheimer’s Association International Conference (AAIC) 2013 in Boston, the project obtained whole genome sequences on the largest cohort of individuals related to a single disease – more than 800 people enrolled in the Alzheimer’s Disease Neuroimaging Initiative (ADNI).

The genome sequencing data – estimated to be 200 terabytes – will be housed in and available through the Global Alzheimer’s Association Interactive Network (GAAIN), a planned massive network of Alzheimer’s disease research data made available by the world’s foremost Alzheimer’s researchers from their own laboratories, and which also is being publicly announced today at AAIC 2013. GAAIN is funded by an initial $5 million dollar investment by the Alzheimer’s Association, made possible due to the generous support of donors.

“The Alzheimer’s Association is committed to creating open access to research data, and we believe GAAIN will transform how neuroscience data is shared and accessed by scientists throughout the world,” said Maria Carrillo, Ph.D., Alzheimer’s Association vice president of Medical and Scientific Relations. “By fostering a higher level of global data sharing, GAAIN will accelerate investigation and discovery in Alzheimer’s through a system comparable to a search engine like Google or Bing for relevant data.”

“With the addition of more than 800 whole genomes on ADNI subjects that can be linked to the current rich dataset, ADNI data will be even more useful to scientists who are seeking new approaches to treatment and prevention of Alzheimer’s disease,” said Robert C. Green, M.D., M.P.H., of Brigham and Women’s Hospital and Harvard Medical School, who led the ADNI sequencing project. “ADNI is a leader in open data sharing, having provided clinical, imaging and biomarker data to over 4,000 qualified scientists around the world, which has generated over 700 scientific manuscripts.

First, Massive Whole Genome Sequencing Project in Alzheimer’s Disease

Whole genome sequencing determines all six billion letters in an individual’s DNA in one comprehensive analysis. The raw data from the ADNI project is being made available to qualified scientists around the globe to mine for novel targets for risk assessment, new therapies, and much-needed insight into the causes of the fatal brain disease. The new data may enable scientists to better understand how our genes cause and are affected by bodily changes associated with Alzheimer’s disease.

ADNI enrolls people with Alzheimer’s disease, mild cognitive impairment, and normal cognition who have agreed to be studied in great detail over time. The goal is to identify and understand markers of the disease in body fluids, structural changes in the brain, and measures of memory; the hope is to improve early diagnosis and accelerate the discovery of new treatments. ADNI is led by Principal Investigator Michael W. Weiner, M.D., of the University of California San Francisco and the San Francisco VA Medical Center. Dr. Green collaborated on managing the sequencing efforts with Arthur Toga, Ph.D., of UCLA and Andrew J. Saykin, Psy.D., of Indiana University. The actual genome sequencing was performed at Illumina, Inc.

ADNI is a public-private research project led by the National Institutes of Health (NIH) with private sector support through the Foundation for NIH. Launched in 2004, ADNI’s public-private funding consortium includes pharmaceutical companies, science-related businesses, and nonprofit organizations including the Alzheimer’s Association and the Northern California Institute for Research and Education.

The Global Alzheimer’s Association Interactive Network (GAAIN)

Data-sharing has already greatly benefitted scientific disciplines such as genetics, molecular biology, and the physical sciences. Data-sharing in genetics has led to dramatic advances in understanding the risk factors underlying complex diseases. The Alzheimer’s Disease Neuroimaging Initiative (ADNI) is a compelling example of dozens of geographically-dispersed researchers working together to share their data while making it freely available to others for analysis and publication.

“GAAIN is similar in spirit and goals to other ‘big data’ initiatives that seek to greatly improve the tools and techniques needed to access, organize, and make discoveries from huge volumes of digital data,” Carrillo said. “The advent of cloud computing makes it possible to link databases throughout the world and expand their data processing capability significantly to benefit the research community.”

Carrillo will supervise the development of GAAIN in conjunction with co-principal investigators Art Toga, Ph.D., of the Laboratory of Neuro Imaging (LONI) at the University of Southern California and Giovanni Frisoni, M.D., of the National Center for Alzheimer’s Disease Research and Care and the Instituto di Ricovero e Cura a Carattere Scientifico (IRCCS), Fatebenefratelli Hospital, Italy. Enrique Castro-Leon, Ph.D., who will serve as a consultant, is an enterprise and data center architect for strategic partner Intel Digital Enterprise Group.

GAAIN is built on an international database framework already in use by thousands of scientists and local computational facilities in North America and Europe. The network makes research data available free-of-charge for searching, downloading, and processing across a cloud-based, grid-network infrastructure accessible anywhere through Internet access.

The key to GAAIN’s innovation is its federation of data, which is unprecedented for such a system. GAAIN leadership will invite scientists conducting qualified studies to become partners by permitting GAAIN to link directly to their databases. This will enable researchers to add continually to their data sets and keep all data in GAAIN current and dynamic. It also will enable the scientists to retain control over access to their data, which the Association believes will be important to encouraging participation.

“This is unprecedented and of the utmost importance in brain research, where sometimes thousands of examples are required to observe even the smallest change in the brain,” said Giovanni Frisoni, M.D., neurologist and deputy scientific director at the National Center for Alzheimer’s Disease Research and Care at the IRCCS. He will lead the work of GAAIN in Europe.

“Through GAAIN we envision combining massive amounts of data from multiple sources across many subjects participating in numerous studies,” said Art Toga, Ph.D., professor of neurology at UCLA and director of LONI. “This will provide more statistical power than ever before.”

Source: Alzheimer’s Association

Crescendo Bioscience to Present New Data on Vectra DA Use to Assess Radiographic Progression Risk in Patients with Rheumatoid Arthritis Treated with Traditional and Biologic Therapies at the European League Against Rheumatism Annual Meeting (EULAR)

Crescendo Bioscience, a molecular diagnostics company dedicated to developing and commercializing quantitative blood tests for rheumatoid arthritis (RA) and other auto-immune diseases, announced today that it will present data from ten different studies that further support the important role Vectra® DA can play in managing Rheumatoid Arthritis (RA) at the European League Against Rheumatism (EULAR) Annual Meeting held in Madrid, Spain, on June 12-15. EULAR is the largest gathering of rheumatology healthcare professionals in Europe. Vectra DA is an objective, validated blood test that provides rheumatologists with a score of 1-100, giving biological insight into the level of disease activity of rheumatoid arthritis. Data presented at EULAR will demonstrate Vectra DA’s ability to assess risk of radiographic progression (joint damage over time) in patients with RA currently treated with traditional and biologic agents, including TNF inhibitors. In addition, data will show how Vectra DA can detect a high level of RA disease activity in patients with a low C-reactive protein (CRP) without being affected by fibromyalgia, a painful non-inflammatory condition that can co-exist with RA.

This week, researchers will present data from a study conducted by the University of Occupational and Environmental Health in Kitakyushu, Japan, A Multi-biomarker Disease Activity (Vectra DA Algorithm) Score is Associated with Radiographic Outcomes in RA Patients Treated with TNF inhibitors (#SAT0012) . This study found that patients who were being treated with adalimumab, etanercept or infliximab and had a low Vectra DA score (29 or less) in at least two of three visits over one year showed little or no radiographic progression. In contrast, patients with high scores (greater than 44) for at least two of three visits had a much higher risk of clinically relevant radiographic progression. In addition, researchers found that change in the Vectra DA score over the first six months of treatment correlated with radiographic outcomes in the first year. This is the first time risk of radiographic progression in patients treated with TNF inhibitors was assessed using Vectra DA over time.

“We know that anti-TNF drugs have been shown to help minimize the overall amount of radiographic progression,” said Yoshiya Tanaka, MD, PhD, Professor and Chairman, University of Occupational and Environmental Health, Kitakyushu, Japan. “This study underscores the clinical utility of Vectra DA to objectively assess which patients remain at risk of radiographic progression despite anti-TNF therapy. This information could be important in helping rheumatologists confirm or potentially revise their treatment plan.”

“This study demonstrates the additional value Vectra DA can bring to the overall RA patient management experience,” said Oscar Segurado, MD, PhD, Chief Medical Officer at Crescendo Bioscience. “With a number of RA drugs available today, and more than 50 agents in development, a quantifiable disease activity measurement test like Vectra DA can be a true asset for physicians.”

Researchers will also present new data regarding use of Vectra DA in patients with both RA and fibromyalgia. In Application of a Multi-Biomarker Disease Activity (Vectra DA) Score for Assessing Rheumatoid Arthritis Patients with Low CRP or Fibromyalgia (#SAT0099), researchers from the Brigham and Women’s Hospital and Harvard Medical School showed that in patients with RA, traditional methods of disease assessment, including tender joint count, DAS28-CRP, and Patient Global Assessment were markedly increased by the presence of fibromyalgia, a painful non-inflammatory syndrome that can confound the assessment of patients with RA. In contrast, the Vectra DA test measured essentially the same level of disease activity in patients with RA independent of the presence of fibromyalgia, which highlights the value of the objective nature of the test.

“Vectra DA provides additional information about disease activity that is not provided by other assessment tools such as C-reactive protein (CRP),” said Segurado. “This study showed that in patients with low CRP, nearly half had Vectra DA scores in the moderate to high disease activity range, indicating that their RA was actually more active than originally found with CRP. This information will help physicians attain better insight to the underlying biology of the disease.”

Additional Poster Highlights

A study selected by EULAR will be part of the Poster Tour (FRI0098) Friday, June 14 between 11:45 am and 1:30 pm, Biomarker-Based Estimates of Risk of Radiographic Progression in the Leiden Early Arthritis Cohort, and researchers from the Leiden University Medical Center, Leiden, the Netherlands will discuss the use of Vectra DA as a tool to estimate the risk of radiographic progression in RA.

“Using the Vectra DA score, we were able to see a correlation between the score and risk of radiographic progression over 12 months,” said Tom W.J. Huizinga, M.D., Head of the Department of Rheumatology, Leiden University Medical Center, Leiden, the Netherlands and primary investigator. “This tells us that Vectra DA can be helpful in identifying patients at high risk for radiographic progression and, thus, give rheumatologists more information to help prevent future progression.”

Another poster, A Multi-Biomarker Disease Activity Blood Test (Vectra DA) Correlates with Radiographic Progression in Early Rheumatoid Arthritis: Results from the SWEFOT Trial (#FRI0060), focused on use of Vectra DA in assessing risk of radiographic progression in early RA. The SWEFOT study is the Swedish Pharmacotherapy Trial out of the Karolinska Institutet in Stockholm.

In early RA patients starting methotrexate, the study found that Vectra DA’s score, when assessed at baseline, significantly correlated with radiographic progression in the first year. “A high MBDA score at baseline was associated with a higher risk of radiographic progression, even in patients who had moderate disease activity by DAS28 or low CRP at baseline,” said Ronald F. van Vollenhoven,M.D., Ph.D., Professor and Chief, Unit for Clinical Therapy Research, Inflammatory Diseases (ClinTRID), Chief, Clinical Trials Unit, Department of Rheumatology, the Karolinska Institute and primary investigator of the study.

Other Vectra DA Posters Presented at 2013 EULAR Annual meeting

Additional study results (presented in six posters listed below) further demonstrate and confirm the ability of Vectra DA to objectively assess disease activity and/or potentially identify risk for radiographic progression in early- and later-stage RA patients.

Poster #FRI0061

Multi-Biomarker Disease Activity (MBDA) Score and the 12 Individual Biomarkers in Early Rheumatoid Arthritis Patients Relate Differently to Clinical Response and Radiographic Progression: Results from SWEFOT Trial; K. Hambardzumyan, Karolinska Institutet, ClinTRID, Stockholm, Sweden, and other collaborators.

Poster #FRI0062

Evaluation of a Multi-Biomarker Disease Activity (Vectra DA Algorithm) in Early Rheumatoid Arthritis and Unclassified Arthritis Patients; K. I. Maijer, Department of Clinical Immunology and Rheumatology, Academic Medical Center/University of Amsterdam, Amsterdam, the Netherlands and other collaborators.

Poster #FRI0066

Behavior of the Multi-Biomarker Disease Activity (Vectra DA Algorithm) Score and Components in Patients with Rheumatoid Arthritis Treated with Tocilizumab; K. Hanami, The First Department Of Internal Medicine, University of Occupational and Environmental Health, Kitakyushu, Japan, and other collaborators.

Poster # FRI0075

A Multi-Biomarker Disease Activity (Vectra DA Algorithm) Score and Components are Associated with Sustained Clinical Remission in Rheumatoid Arthritis: the REMIRA Study; M. H. Ma, Academic Department of Rheumatology, King’s College London, London, United Kingdom and other collaborators.

Poster #FRI0079

Response to MTX Plus Prednisone in CAMERA II Using a Multi-Biomarker Disease Activity Test (Vectra DA) and DAS28-ESR; M. S. Jurgens, Rheumatology & Clinical Immunology, UMC UTRECHT, Utrecht, Netherlands and other collaborators.

Poster #SAT0033

Characterization of the Multi-Biomarker Disease Activity (Vectra DA Algorithm) Score in a Subgroup of Patients from the Epidemiological Investigation of Rheumatoid Arthritis (EIRA) Cohort Receiving Methotrexate; W. Li, Crescendo Bioscience, Inc., South San Francisco and other collaborators.

Source: GlobeNewswire

Cancer Biomarker Study Data Presented at the 2013 AACR Meeting

As we’ve done in previous years here at Biomarker Commons (AACR 2011 and AACR 2012), here’s a roundup of eight research studies on cancer biomarkers that were presented last month at the American Association for Cancer Research (AACR) Annual Meeting in Washington, DC. The theme of this year’s meeting was “Personalizing Cancer Care Through Discovery Science.”

  • Biomarker Analysis Identified Women Most Likely to Benefit From T-DM1

    According to data from a subanalysis of a phase III clinical trial that led the U.S. Food and Drug Administration to approve trastuzumab emtansine (T-DM1) in February, the amount of HER2 in tumors of women with metastatic, HER2-positive breast cancer might determine how much they benefit from the drug. The findings were presented by José Baselga, M.D., Ph.D., physician-in-chief at Memorial Sloan-Kettering Cancer Center in New York.

    Source: AACR

  • Novel Serum Biomarker Bilirubin Predicted Lung Cancer Risk in Smokers

    Researchers from MD Anderson Cancer Center in Houston, Texas, used a unique multiphase study design for the metabolomics profiling of serum samples from non-small lung cancer patients, and showed that bilirubin is a potential biomarker for lung cancer risk prediction. Men who were smokers and had low bilirubin levels had increased risk for cancer incidence and mortality.

    Source: AACR

  • Biomarkers Discovered That May Help Predict Response to Drugs Targeting KRAS-mutated NSCLC

    Massachusetts General Hospital scientists have identified biomarkers that may help predict whether patients with KRAS-mutated non-small cell lung cancer (NSCLC) will respond to concurrent treatment with an MEK inhibitor and a PI3 kinase inhibitor, a drug combination currently being investigated in ongoing clinical trials.

    Source: AACR

  • Screening Blood Samples for Cancer-driving Mutations More Comprehensive Than Analyzing Traditional Tumor Biopsy

    Using a tool called BEAMing technology, which can detect cancer-driving gene mutations in patients’ blood samples, researchers from Dana-Farber Cancer Institute and Harvard Medical School showed that were able to identify oncogenic mutations associated with distinct responses to therapies used to treat patients with gastrointestinal stromal tumors (GIST).

    Source: AACR

  • More Accurate Markers Identified for Detecting Response to Epigenetic Drugs for Myelodysplastic Syndromes

    Researchers from the University of Southern California, Los Angeles, have identified and validated two DNA methylation markers that could help physicians better determine a patient’s response to DNA methyltransferase inhibitors (DNMTi) for the treatment of myelodysplastic syndromes (MDS).

    Source: AACR

  • Cohort Study Indicates That Selenium May Be Protective Against Advanced Prostate Cancer

    According to a data presented by researchers from Maastricht University in the Netherlands, a greater level of toenail selenium is associated with a significant decrease in the risk for advanced prostate cancer.

    Source: AACR

  • Comprehensive Genomic Analysis Identified Alterations in Head and Neck Cancer That Could Lead to Targeted Therapy

    A National Institutes of Health project to catalog the genetic alterations responsible for several types of cancer, in particular those with a poor prognosis, finds that head and neck squamous cell carcinomas are genomically heterogeneous. However, those cancer with certain distinctive patterns could be amenable to specific targeted therapies.

    Source: AACR

  • Novel Drug Combination Showed Antitumor Activity in Patients With Incurable BRCA-deficient Cancers

    Researchers from Dana-Farber Cancer Institute and Harvard Medical School have identified two orally available experimental drugs — sapacitabine and seliciclib — from phase I trial data that, when given sequentially, work together to elicit antitumor effects in patients with incurable BRCA-deficient cancers.

    Source: AACR

Firm Hopes Big Data Can Personalize Health Care

When Colin Hill’s father was diagnosed with later-stage prostate cancer last summer, he was treated the same as every other patient with the illness.

This standardized approach bothered Hill, who believes medicine should approach each patient’s illness as unique, with medication tailored to the person’s history and biology.

“You show up to the hospital, and it’s like Groundhog Day,” Hill said, with patients being cared for the same way, over and over again. “It’s this outdated standard of care created for this hypothetical average patient. But no one’s an average patient.”

A genetic analysis of the tumor in his 69-year-old father, Foster Hill, found he had a genetic variant of the cancer that does not usually respond well to the hormone therapy Lupron, the current standard of care. But not knowing what else would work, doctors gave Foster Hill Lupron anyway. Luckily, the treatment seems to be helping, and his father’s outlook is much improved.

Hill hopes a Kendall Square company he founded 13 years ago, GNS Healthcare, will eventually improve medical care for his father — and for countless others — by providing personalized treatment. GNS is among the leaders in using Big Data analytics to learn more about diseases, patients, and treatments.

With data from thousands of cases, GNS uses artificial intelligence to determine what treatment made the crucial difference for each patient.

The company is deploying enormous computing power to produce a more complete understanding of treatments for rheumatoid arthritis, diabetes, cancers, and other illnesses.

For example, it is working with the Dana-Farber Cancer Institute and Mount Sinai Medical School to build a computer model of multiple myeloma, so researchers can better understand what works well for patients today, as well as develop more effective treatments for the blood cancer. It is involved in a similar collaboration with Brigham and Women’s Hospital and several other partners to learn more about multiple sclerosis.

Harvard Medical School recently agreed to use a GNS computing platform to analyze how cells replicate or transform into different types, for insights into­ conditions such as cancer and neurodegenerative diseases, Hill said.

And the company has a partnership with the Centers for Medicare & Medicaid Services and Health Services Advisory Group to assess health care quality measures, as well as other recent deals with pharmaceutical companies, hospitals, and advocacy groups, and the insurance giants Aetna and Blue Cross Blue Shield.

“It’s exciting times for us,” Hill said, after 13 years of developing his approach to analyzing health care. “We are now in the thick of things.”

Hill did not always have such an absorbing interest in science. He went to college at Virginia Tech — mainly to play tennis. “I was more serious than I was good,” he quipped.

But while there, he became fascinated by physics and chaos theory — the idea that complex patterns could result from simple rules.

His imagination was stoked by a summer job in 1996 at Santa Fe Institute, an interdisciplinary research center focused on highly complex issues. Hill then went on to graduate from McGill and then Cornell University.

By then, the Human Genome Project was becoming a reality, capturing the attention of many scientists, including a young Hill.

“That’s when two and two came together,” Hill said. “It was like ‘Oh yeah, the stuff we’re doing, though it’s pretty theoretical, it is going to be the thing that links these pieces together,’ ” including chaos theory, genetics, Big Data, and health care.

Now he’s in the middle of the so-called Big Data revolution in health care. Companies such as GNS have an enormous capacity for crunching troves of information on patients, diseases, and medical outcomes collected by medical providers, insurers, and other big players.

Hill likes to say he wants GNS to capture the “data exhaust thrown off” by every interaction a patient has with the health care system, from the doctor’s office to the hospital to the pharmacy. A bad reaction to medication is a data point worth having; ditto for other side effects, as well as results of all kinds of procedures and interventions — bad or good.

While such data sets are getting easier to find, Hill said, genetic information is still too expensive to be truly useful.

“What we don’t have yet for my dad and for other men with prostate cancer is a large coherent set of data on prostate cancer patients that includes the molecular level,” Hill said.

With information aggregated from thousands of cases, Hill said, GNS uses artificial intelligence algorithms developed out of chaos theory to determine what treatment made the crucial difference for each patient, and with it what is likely to work best for the next patient — rather than simply trying one medication after another, as is often done today.

“What we’re trying to get at is not just patterns and trends, but reverse engineer the mechanisms that gave rise to the data,” he said. “We’re trying to find the cause-effect relationships within the data.”

This ability to predict results is what sets GNS apart, said Dr. Atul Butte of Stanford University, one of the academic leaders of the Big Data movement. That’s the “nifty part of their technology,” Butte said.

Alexis Borisy, a partner at the Boston life sciences venture capital firm Third Rock Ventures, said GNS is in the vanguard of Big Data companies analyzing health care information.

“They’ve had a chance to learn, refine, and they’ve kept with it so they’ve had a lot of experience to build on,” Borisy said.

He and Hill have known each other since they were young business executives more than a decade ago, and he said he has tremendous respect for Hill’s intelligence, persistence, and communication skills.

“He is one of the visionaries in the space,” said Borisy, who also serves as chairman of Foundation Medicine, a molecular information company, and interim chief executive of Warp Drive Bio, both of Cambridge. “I think it’s fair to say he’s kept GNS growing and building by the force of his personality and the force of his efforts.”

Source: The Boston Globe

Better Diagnosis of Acute Heart Failure Using Pronota’s Novel Biomarker

Two independent validation studies demonstrate that Pronota’s biomarker CD146 significantly improves the diagnosis of acute heart failure for patients with shortness of breath. The biomarker, measured in blood, provides clinicians with unique additional information allowing better treatment of this challenging group of patients.

Current diagnosis for acute heart failure is limited

Current clinical practice for triaging patients with shortness of breath includes the measurement of specific peptides (B-type natriuretic peptides: BNP or NT-proBNP). Despite the widespread use of these biomarkers, there is still much room for improvement. “Natriuretic peptides have become standard tools to support making the correct diagnosis in patients with shortness of breath. However, clinicians clearly recognize the limitations of natriuretic peptides. The potential value of another biomarker to improve the diagnostic accuracy of BNP or NT-proBNP is considerable,” commented Prof. J. Januzzi (Massachusetts General Hospital, Harvard Medical School).

Pronota’s novel heart failure marker for accurate diagnosis

Pronota identified the biomarker CD146 from an unbiased proteomics effort. Its performance has now been confirmed in two independent studies totaling over 500 patients. Prof. A. Mebazaa (INSERM, Paris, France), principal investigator for the validation studies, commented: “It is exciting to see that novel biomarkers with underlying biological processes completely different from currently used biomarkers can still be discovered and validated. This not only provides more insight into the underlying disease mechanism, it also gives the physician tools to improve the management and care of heart failure patients. Pronota’s approach in this respect is unique and has proven to deliver on numerous occasions.”

Launch forecast: 2014

“Data from early verification and marker characterization studies were already highly exciting, but the recent independent validation studies exceeded our expectations and would not have been possible without the support of our network of key opinion leaders in the field” commented Katleen Verleysen, CEO of Pronota NV. “We anticipate launching this product in 2014, so that clinicians may get access to the tools they need to improve the treatment and care of their patients.”

Source: Pronota