Showing 13 ideas for tag "precision"

Goal 3: Advance Translational Research

Understanding Chronic Lung Disease Subtypes

What are the subtypes of chronic obstructive lung disease that share a common pathogenesis and can be a basis for precision medicine?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Chronic Obstructive Pulmonary Disease (COPD) is a complex heterogeneous syndrome. The current approach of regarding this disease as a single entity has limited the ability to develop effective therapies and prevention. Understanding the major subtypes of COPD could lead to more biologically relevant disease classifications, improved prognostic information, and precision medicine treatment.

Feasibility and challenges of addressing this CQ or CC

The optimal analytical approaches and data types to define complex disease subtypes have not been determined.

Name of idea submitter and other team members who worked on this idea Ed Silverman, James Crapo and COPDGene Executive Committee

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32 net votes
50 up votes
18 down votes
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Goal 2: Reduce Human Disease

Precision medicine in non-malignant lung diseases

NIH has a major initiative in Precision Medicine, including whole genome sequencing. In contrast to cancer, mutations with large clinical effects are expected to be uncommon in most non-malignant chronic diseases, such as asthma and COPD. Other data types such as gene expression, biomarkers, and micro RNAs must be combined with clinical and imaging phenotyping to advance Precision medicine in non-malignant lung diseases.... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

The goal is to combine clinical and molecular data to identify subtypes of patients within the major chronic respiratory diseases. Understanding molecular pathways will first lead to more appropriate drug repositioning and eventually novel drug development.

Feasibility and challenges of addressing this CQ or CC

NHLBI has many cohorts of subjects with chronic lung diseases with longitudinal clinical characterization, many with banked biospecimens. It is quite feasible to perform genomic, epigenetic and biomarker assays on these specimens. Based on these results, hypothesis-based targeted profiling can be done in prospective studies.

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12 net votes
15 up votes
3 down votes
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Goal 4: Develop Workforce and Resources

Preserving and promoting expertise in integrative physiology

From my perspective, one of the key “critical challenges” facing the NHLBI in particular, and medical science in general, is to avoid being blinded by the promises of the reductionists in the “personalized, precision medicine” of the future. In order to understand the advances being made at the molecular level, we need to preserve and promote expertise in truly integrative physiology, what I like to call “PHYSIOMICS”.... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Unfortunately, human physiologists are being squeezed out of the medical industrial complex by the basic scientists on one end, and the epidemiologists on the other. Most departments of medicine now require on 80/20 commitment to have a significant research component of an academic career, and it is becoming increasingly difficult for those few of us physiologists remaining to compete with the pressures of both research funding and clinical mandates. I urge the leadership at NHLBI to preserve a strong focus on human physiology, and continue to support the small, but high resolution studies that are required to answer key research questions. I would submit that studying an individual patient’s unique physiology is as much “personalized” or “precision” medicine as it is to read their genome. Remember, despite billions of dollars of research support, there remains nothing better to predict the risk of diabetes, than a simple measure of waist size!

Name of idea submitter and other team members who worked on this idea Benjamin Levine

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6 net votes
16 up votes
10 down votes
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Goal 3: Advance Translational Research

Addressing Unrecognized and Over Diagnosis of COPD

How can we create precision diagnostics for COPD in practice settings that will help inform the transition from screening to better diagnosis and treatment strategies and that will help identify patients or communities at highest risk for unrecognized or over diagnosed COPD.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

About 12 million individuals are estimated to have undiagnosed COPD and in most cases patients aren’t diagnosed until they have lost over half of their lung function leading to worse outcomes short and long term. Conversely there are challenges with over and mis diagnosed COPD that can result in over treatment and incorrect treatment. Fine tuning screening, diagnostic and management tools can result in earlier and proper identification of disease, earlier initiation of risk mitigation and/or treatment strategies and improved health outcomes as well as improved efficiencies in the healthcare system.

Name of idea submitter and other team members who worked on this idea COPD Foundation, Nancy Leidy, COPDF MASAC

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11 net votes
12 up votes
1 down votes
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Goal 1: Promote Human Health

Predictive analytics to engage healthy behaviors and maintain health while reducing cost

Predictive Health employs the principle that using modern health testing and predictive analytics will better define true health (not just absence of disease) and, in combination with large-scale data analytics, will facilitate predicting deviations from the healthy trajectory earlier than traditional disease diagnosis, thus allowing more effective and less costly interventions to maintain health. Predictive Health educates... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

By addressing this CC the health of the nation will be improved: better national and individual understanding of health, greater longevity of sustained health and productivity, reduced costs of healthcare by focusing on health than on disease diagnosis and management.

Feasibility and challenges of addressing this CQ or CC

The Emory/Georgia Tech Predictive Health Institute (http://predictivehealth.emory.edu) was founded ~10 years ago by launching educational (http://predictivehealth.emory.edu/education/index.html) and scientific (http://predictivehealth.emory.edu/chd/index.html) programs to achieve the Predictive Health goals. The scientific approach created a prospective longitudinal cohort of individuals who have been richly phenotyped according to traditional medical testing (clinical laboratory, stress testing, etc) and research testing (genomics, metabolomics, regenerative cell potential, oxidative stress) to create the deepest understanding of current and future health. The success of the Predictive Health Institute demonstrates the feasibility and potential success of such a critical challenge to both human health and healthcare expenditures.

Name of idea submitter and other team members who worked on this idea Greg Martin, for the Emory/Georgia Tech Predictive Health Institute

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5 net votes
9 up votes
4 down votes
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Goal 3: Advance Translational Research

Durable gene activity map at the individual level

A durable gene activity map of the individual to understand when certain gene sets are on vs off or dysfunctional over an individual’s lifetime as one way of guiding the precision of medicine for that patient. It would need to be person portable and universally exportable and interpretable across all of the EHRs.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Committee/Council

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3 up votes
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Goal 2: Reduce Human Disease

The importance of cosidering sex and gender in presicion medicine

Precision medicine will be invested in across NIH, as per the President's "Precision Medicine Initiative". It is critical that the population base be reflective of the US population, including 50% women. Gender, especially as it relates to exposures, must be a dominant consideration, as these factors are critical to the development of human disease and therefore will be important to prevention.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Precision medicine that can be applied accurately to different groups within o our population, in particular women and racial and ethnic minorities.

Feasibility and challenges of addressing this CQ or CC

Achieving this goal is feasible and essential.

Name of idea submitter and other team members who worked on this idea Paula Johnson

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2 net votes
2 up votes
0 down votes
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Goal 2: Reduce Human Disease

Balancing Risks and Benefits: How Do Clinical Guidelines in Cardiovascular Medicine Promote the Health of an Individual?

Much of the hopes for precision medicine (as outlined Dr. Dr. Collins) are based on deriving large amounts of genomic, proteomic, epigenomic and metabolomic data on large cohorts of patients. It will take decades to build these cohorts and even more time to analyze them and derive specific conclusions on how these will help individualize treatments.

However, there is a pressing need for how to individualize contemporary... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Decisions on whether or not to place a patient with atrial fibrillation on chronic anticoagulation or on statin therapy are often based on guidelines and cardiovascular risk calculators.

Patients with a higher risk of stroke are more likely to receive anticoagulation and patients with a higher risk of a myocardial infarction are more likely to receive statin therapy.

However, these cardiovascular risk calculators do not really take into account the potential side effects and impact on the lifestyle of the patients.

Physicians will stop anticoagulation in a patient with atrial fibrillation if the patient has suffered a life-threatening bleed but there are no specific evidence-based guidelines as to how one should proceed if the bleeding is minor.

it is easy to compute the cardiovascular risk and overall mortality benefit of placing a patient on statins but how does one factor in the impact that statins have on the quality of life of an individual?

Developing novel evidence-based approaches to individualize therapies that factor in cardiovascular benefits as well as potential side effects and diminished quality of life could have a major impact on appropriately using treatments and reduce the arbitrariness of some medical decisions.

Name of idea submitter and other team members who worked on this idea Jalees Rehman

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1 up votes
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Goal 3: Advance Translational Research

Translational Bioinformatics Spanning Multiple Scales of Biologic Complexity to Implement Precision Pulmonary Medicine at the Po

What translational bioinformatics tools could be used in pulmonary medicine to allow multidimensional, multi-scale modeling of clinical and biomolecular data to assist clinical decision-making?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Deployment of bioinformatics tools to construct multi-dimensional, multi-scale models of pulmonary (mal)functioning from large heterogeneous data sets spanning biological molecules, subcellular compartments, signaling pathways, cells, tissues, organs, organ systems and clinical therapeutics trials to predict actionable precision medicine for clinicians at the point of pulmonary care.

Feasibility and challenges of addressing this CQ or CC

A variety of existing powerful informatics methods for integrating a vast wealth of clinical and high-dimensional data across DNA to organism compartments to develop multi-scale modeling approaches to improve point-of-care precision medicine. Consistent with a continuous learning healthcare system, precision medicine modeling is recursive, tentative pending better understanding and therefore continuously learning.
Fundamental to implementation of precision medicine is the ability to extract heterogeneous data from basic and clinical research to be integrated systematically into clinical practice in a cohesive and large-scale manner. Deployment of precision medicine models to predict (mal)functioning progression and response the treatment in daily practice relies strongly on the availability of an efficient bioinformatics platform that assists in the translation of basic and clinical science knowledge.

Name of idea submitter and other team members who worked on this idea NHLBI Staff

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-2 net votes
10 up votes
12 down votes
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Goal 2: Reduce Human Disease

Bringing Personalized Biochemistry and Biophysics to Bear on Problems of Personalized Heart, Lung and Blood Medicine

Precision medicine will provide unprecedented opportunities to tailor health care based on knowledge of personal patterns of genetic variations. These variations usually impact protein or RNA sequences, resulting in altered properties. These alterations can result in increased susceptibility to a particular disease or intolerance to common therapeutics. To take full advantage of knowing a patient’s set of gene variations,... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

As detailed in the attached review (Kroncke et al. Biochemistry 2015, 54, 2551−2559) the successful practice of personalized medicine will in many cases require a molecular-level understanding of the nature of the defects that are caused by disease-predisposing genetic variations. As widespread personal genome sequencing becomes routine, numerous genetic variations (many millions) of uncertain significance will be discovered. Using both experimental and computational tools associated with the fields of biochemistry, biophysics, and structural biology it is in many cases possible to ascertain whether a newly-discovered gene variation adversely impacts a critical protein or RNA function and, if so, how. Among various clinical applications this information can be used (i) to project whether a patient not currently showing symptoms for a particular disease is likely to present with that disease in the future (sometimes enabling prophylactic therapy), (ii) to help establish the molecular etiology of a disease currently afflicting the patient, and (iii) to guide the therapeutic strategy pursued for that patient.

Feasibility and challenges of addressing this CQ or CC

My lab is already participating in a project (RO1 HL122010) with two other labs (those of Drs. Jens Meiler--Vanderbilt and Alfred George--Northwestern) to develop personalized biochemical and biophysical approaches for application to genetic variations impacting the KCNQ1 gene, potentially predisposing patients to long QT syndrome, a cardiac arrhythmia. However, our project deals with one gene and one disorder only. There clearly is a need for improved and expanded communication and collaboration between those practicing personalized/precision medicine and those who are well-equipped to provide medically actionable molecular insight using the approaches of personalized biochemistry, biophysics, and structural biology.

Name of idea submitter and other team members who worked on this idea Charles R. Sanders, Prof. of Biochemistry, Vanderbilt University (With Drs. Alfred George--Northwestern University and Jens Meiler--Vanderbilt University)

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-2 net votes
9 up votes
11 down votes
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Goal 3: Advance Translational Research

Use isogenic iPS cells to advance Precision Medicine

The goals of Precision Medicine can be achieved if we determine the biological basis of disease-associated variants for NHLBI diseases. Advances in genetic research have yielded hundreds of disease-associated DNA polymorphisms, yet we lack robust methods to experimentally test their functional relevance in human cells. Determining the molecular and cellular basis of human phenotypic variation is one of the great challenges... more »

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Critical Challenge (CC)

Details on the impact of addressing this CQ or CC

Identifying how disease mutations result in cellular phenotypes will provide an experimental basis for Precision Medicine. Advances in genome engineering and iPS cell technology now offer a unique opportunity for NHLBI researchers to make a focused effort to produce isogenic disease models, to determining the function of putative disease loci. Just a few years ago, the barriers to this type of project seemed insurmountable, as iPS cells were made with damaging DNA insertions, designer nucleases were difficult to make, complex material-transfer agreements (MTAs) inhibited the open sharing of reagents, and cell-engineering methods were cumbersome. Remarkably, all of these barriers have fallen substantially in recent years, to reveal strategic new opportunities. The phenotypes are determined in isogenic human iPS-models, these observations can be applied to animal models, and human clinical studies.

Feasibility and challenges of addressing this CQ or CC

Progress towards this goal is being made, but slow pace does not meet opportunity that the NHLBI community has. The NHLBI has a much larger opportunity than other institutes because so many genetic variants have already been determined via excellent genetic studies using robust physiological phenotypes. The genetic variants provide hypotheses that are ripe for direct experimental testing in isogenic iPS cell models. Fortunately, many diseases of interest to NHLBI can be modeled in iPS-derived tissues. Other part of NIH (e.g. NIMH, NIDA, NIAAA ) lack abundance of high probability genetic "hits" that NHLBI now has. NHLBI should take advantage of this opportunity.

Name of idea submitter and other team members who worked on this idea Bruce Conklin

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-19 net votes
8 up votes
27 down votes
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Goal 2: Reduce Human Disease

Consequences of drug interactions leading to QTc prolongation

Better understand the consequences of drug interactions leading to QTc prolongation. About 1/3 of cardiac ICU patients develop QT prolongation and about 45% receive drugs that are possibly contributing to this problem. The full spectrum of contributors and causes, as well as the patient-centered and health-system-centered clinical outcomes, are not known.

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Details on the impact of addressing this CQ or CC

Reduction in adverse drug events and preventable deaths

Feasibility and challenges of addressing this CQ or CC

Combining the power of predictive analytics of high dimensional data streaming continuously from critically ill patients, combined with precision medicine genomics and metabolomics, makes this imminently feasible.

Name of idea submitter and other team members who worked on this idea Society of Critical Care Medicine Executive Council

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-1 net votes
1 up votes
2 down votes
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Goal 2: Reduce Human Disease

Basic Research & Precision Medicine

How can NHLBI best encourage basic research areas that are critical to the development of precision medicine approaches for lung disease?

Is this idea a Compelling Question (CQ) or Critical Challenge (CC)? Compelling Question (CQ)

Name of idea submitter and other team members who worked on this idea Cystic Fibrosis Foundation

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-2 net votes
3 up votes
5 down votes
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