Summary of Research Activities by Key Approach and Resource
Disease Registries, Databases, and Biomedical Information Systems
The Atlanta physician had never before treated a boy complaining of “numb chin.” He sent the lad to the examining room
to undress and quickly turned to his personal computer. He typed in the term “numb chin” and read from the screen a lengthy
description of an article on just that subject. This information provided the vital clue the physician needed to diagnose
a form of lymphoma. Similar scenes are reenacted thousands of times every day in physicians’ offices, research laboratories,
hospital nurses’ stations, and medical schools–in short, wherever health professionals require information. The system this
physician tapped into is MEDLINE, just one of the National Library of Medicine’s growing numbers of online databases
containing medical references, abstracts, and other essential health information for professionals as well as the general public.
From bench to bedside and from database to desktop, information itself has become a primary driver of progress in the
biomedical and health care enterprise. For example, the volumes of data resulting from sequencing the genomes of thousands
of patients have become primary resources for identifying associations between specific genes and diseases. The data that
flow from large-scale clinical studies, advanced diagnostic and imaging equipment, and electronic medical records is a key
enabler of improvements in clinical practice and individual patient care. Up-to-date information from disease registries
has become a critical resource for studying disease incidence and treatment patterns and forms the basis for public health
interventions. The availability of this and other health information on the Internet enables consumers to play a more active
role in managing their health and further increases demand for reliable and authoritative health information.
The development, deployment, and utilization of disease registries, databases, and other biomedical information systems are
essential to managing large amounts of data for improved health. Such systems permit the efficient collection, storage,
and accessing of biomedical information. Disease registries collect information about the occurrence of specific diseases,
such as cancer and Parkinson's disease, the kinds of treatment that registered patients receive, and other information that
might be relevant to researchers or public health officials. This information can help in identifying causal factors of
disease, assessing the effectiveness of various interventions, and identifying questions of concern to researchers, clinical
professionals, and policymakers. Biomedical databases serve as repositories for a wide range of information, from the results
of scientific or clinical research studies, to genomic information, to standard reference materials (such as genome sequences
or anatomical images), to published journal articles and citations to the medical literature. They are widely used by
biomedical researchers, as well as a growing number of clinicians, public health officials, and consumers.
Increasingly, biomedical databases serve not only as repositories of information, but also as research tools in and of
themselves. Discoveries can be made by examining the information they contain. Scientists can use molecular databases
to study the molecular profiles of individual tumors and create small-molecule anticancer agents to target them. They
can analyze large-scale databases linking genotype and phenotype information from thousands of individuals to identify
the genes associated with particular observable traits (e.g., obesity) or diseases (e.g., diabetes, cancer). In these
ways, biomedical information systems are changing the nature of research itself, and promise to change the nature of
clinical care and public health.
The utility of biomedical information systems rests on many factors, including the quality of the data they contain,
accessibility to the full range of potential users, how easily they can be searched to find relevant and interesting
results, and the availability of useful tools for analyzing the information they contain. New data must be added on a
regular basis, while existing data are maintained or updated to reflect new findings. Improved search tools are needed
to comb through the massive datasets and retrieve relevant results. Standard vocabularies that are used to organize
information and ensure accurate retrieval must be updated to accommodate new concepts and relationships. New analytical
tools are needed to explore increasingly complex questions, such as how the expression patterns of multiple genes are
associated with a particular trait or response. Preserving, protecting, and ensuring the validity and security of
information stored in biomedical databases remains of paramount importance.
Scope of NIH Activities in Disease Registries, Databases, and Biomedical Information Systems
Because of the growing importance of information and its management in biomedical science, clinical care, and public
health, virtually every NIH IC is engaged in the development, deployment, and use of biomedical information systems
that support their mission. Several trans-NIH Roadmap activities also feature the development of significant biomedical
information resources, including the tools, infrastructure, and associated research needed to make databases and
registries more valuable.
Most evident among NIH's biomedical information resources are major scientific databases such as GenBank
(genomic sequence data), PubChem
(small molecules data), and dbGaP
(database of Genotype and Phenotype). These and many similar databases (NLM alone oversees 36) have become indispensable national and international resources for biomedical and health research and public health. DNA sequence data stored at NIH, for example, allowed rapid identification of the first known polio case in the United States since 1999 and the rapid initiation of treatment.
NIH also houses the leading source of authoritative biomedical literature for professional and lay audiences. NLM's exhaustive Medline/PubMed
database, for example, indexes citations to some 5,000 peer-reviewed scientific journals on a regular basis. PubMed Central
, its digital archive of full-text articles, provides online access to a growing number of scientific journal articles deposited by publishers and by NIH-funded researchers who are complying with the NIH Public Access Policy
. These comprehensive resources are widely used by scientists, health care providers, and consumers who seek peer-reviewed information on biomedical and health topics of interest. As another example, peer-reviewed studies from the National Toxicology Program
are used by State, local, and Federal health officials to assess the toxicologic potential of environmental compounds to cause adverse health effects such as cancer.
NIH also works with other Federal and private entities to integrate disease registries for national and local use. For example, for 34 years the Surveillance, Epidemiology, and End Results
(SEER) program has collected and published cancer incidence and survival data from cancer registries covering approximately 26 percent of the American population. SEER information has been the foundation for innumerable studies, including recent research into links between hormone therapy and breast cancer. NIAMS
supports a dozen registries
associated with specific diseases, including lupus, muscular dystrophy, and rheumatoid arthritis.
NIH's work on biomedical information systems goes beyond the establishment of databases and registries. NIH is
also the largest Federal funder of biomedical informatics research, which aims to advance the applications of
computing to biomedicine—for both research and clinical care. Grant programs support research and training in
medical informatics and medical librarianship. NIH also leads the government's efforts to develop standardized
vocabularies and terminology to support interoperability among biomedical information systems and has developed
numerous tools to facilitate data analysis. These efforts aim to create and sustain the biomedical information
infrastructure needed for research, clinical care (including electronic health records), and public health.
Summary of NIH Activities
Expanding and Enhancing NIH Scientific Databases
Keeping pace with the expanding biomedical knowledge base is a continuing challenge for scientists; thus, NIH
devotes considerable attention and resources to developing, expanding, and maintaining tools and resources
for information management. NLM's Medline/PubMed database of the peer-reviewed bioscience literature, for
example, added almost 1.3 million new citations to its archive in the 2-year period of FYs 2006-2007 and now contains
indexed citations of more than 17 million articles, editorials, comments, and other materials. PubMed Central,
NIH's electronic archive of full-text journal articles, passed the 1 million article mark in June 2007. NIH's
online registry of clinical trials, Clinicaltrials.gov
added information on more than 23,000 clinical research studies in FY 2006-2007 and by the end of FY 2007 contained information
on some 47,000 clinical trials conducted in more than 140 countries. Many other NIH databases have seen similar growth,
placing greater demand on NIH's information infrastructure and on the resources needed to input, store, and index
information. Ongoing efforts are needed to streamline such processes and boost their productivity.
Increased utilization goes hand in hand with the expanding content of NIH's databases.
alone logged nearly 900 million searches in FY 2006,
almost twice the level of FY 2003, and Clinicaltrials.gov saw some 500 thousand unique visitors
in June 2007, double the number 2 years earlier. Some of this increase is attributable to an
expanding scope of users—not just biomedical researchers, but also clinicians, consumers,
and other practitioners. NIH actively endeavors to make its information resources more
accessible to varied types of users, as illustrated by its work on
NLM's comprehensive health information source for consumers and health professionals, and
, the Wireless
Information System for Emergency Responders. WISER makes information available to emergency
responders from NIH's TOXNET
databases. TOXNET, is a cluster of 14 large databases covering toxicology, hazardous chemicals,
environmental health, and related topics. It has been used by toxicologists for decades, assisting
them in locating toxicology data, literature references, and toxic release information on particular
chemicals, as well as in identifying chemicals that cause specific health effects. To make these
resources more useful to first responders at the scene of a disaster, NIH developed the WISER
system, which enables wireless access to a selection of the most relevant data for emergency
responders. WISER can be installed on personal digital assistants, providing emergency personnel
with access to critical information for identifying and safely cleaning up spilled chemicals,
understanding their health effects, treating exposed victims, and assessing environmental impact.
A Web-based version of WISER, released in FY 2006, can be accessed from any Web-enabled device.
WISER was used to access information on dangerous chemicals to which Hurricane Katrina victims
may have been exposed.
Genomic Information Systems
NIH also has made great strides in developing information resources to support genetics research.
NIH has long supported genetic information resources through widely used repositories such as
the NIH genetic sequence database. More recent efforts have aimed to support the analysis of
data from genome-wide association studies, which explore the connection between specific genes
(genotype information) and phenotype information, such as observable traits
(e.g., blood pressure, weight) or a particular disease. NIH's
(database of Genotype and Phenotype) was launched in December 2006 to house data from a number of
genome-wide association studies. By the end of FY 2007, dbGaP contained more than 12 large datasets,
including genetic analyses from the landmark
Framingham Heart Study
and studies of age-related eye diseases and Parkinson's disease. The wide availability of
information linking genotype to phenotype should help researchers better understand gene-based diseases
and speed development of effective therapies.
Several NIH ICs have established genetics repositories to accelerate research and multidisciplinary
collaborations in specific disease areas. Programs such as the
NIMH Genetics Repository
the NINDS Human Genetics Repository
the NCBI Influenza Virus Resource
the NIA Genetics of Alzheimer's Disease Data Storage Site
and the National Database for Autism Research
give researchers access to vast storehouses of genetic and genomic data, DNA samples, and clinical data,
along with informatics tools designed to facilitate their analyses. For example, the Influenza Virus
Resource database, comprising information obtained from the NIAID Influenza Genome Sequencing Project
and GenBank, contains more than 40,000 influenza virus sequences, including the sequences of more than
2,500 whole influenza genomes. More than 11,000 sequences were added in FY 2006, along with new search
and annotation tools. This resource enables scientists to compare influenza virus strains so that
emergent variants can be more rapidly identified and vaccines developed accordingly. As the library
of viral sequences grows it will be an increasingly important reference to help further understand
how avian viruses spread to humans, and how influenza activity spreads throughout the world.
Disease Registries and Surveillance Systems
NIH-supported disease registries have paid many dividends over the years. Recently, for example,
with the participation of patients from the
Alopecia Areata Registry
, NIH-supported scientists discovered four chromosomal locations that appear to be associated with
susceptibility to this common autoimmune disease, which is characterized by patchy hair loss.
Understanding the mechanisms of the genes found at these locations could lead to the development
of an effective treatment for the disease, which is presently untreatable.
Registries also serve as an effective mechanism to gather data on the incidence, prevalence,
and natural history of diseases. The NIEHS-supported
California Parkinson's Disease Registry
for example, enables researchers to identify the possible environmental and genetic origins
of this progressive neurological disorder suffered by an estimated 1.5 million Americans.
Data in the registry can help to determine whether race, ethnicity, gender, age, environmental
factors, or place of residence influence the likelihood of getting the disease, and can help
track incidence and demographic trends.
Registries also are integral elements of more comprehensive NIH programs designed to monitor
and analyze disease trends in the United States. For example, the
Surveillance, Epidemiology, and End Results (SEER)
program has a rich track record of identifying emerging trends, geographic variation,
ethnic disparities, and other patterns that have provided new directions for epidemiologic
research in cancer etiology and control. SEER data provided critical insight into the
relationship between hormone therapy and breast cancer incident rates. Reported incidents
of breast cancer in the SEER registry began to decline in mid-2002, shortly after a highly
publicized series of reports from the NIH
Women's Health Initiative
(WHI) revealed an association between the risk of breast cancer and the use of hormone therapy.
By analyzing SEER data on breast cancer incidence rates using several key factors such as the
estrogen-receptor status of tumors, WHI researchers demonstrated that the incidence of tumors
most likely to be affected by changes in hormone therapy reflected usage patterns, while
trends for other tumors did not.
Surveillance and monitoring programs are also crucial sources of information and analysis for
policymakers, legislators, public health officials, clinicians, and the public. SEER participates
in Cancer Control P.L.A.N.E.T.
(Plan, Link, Act, Network with Evidence-based Tools), a Web portal that provides links to
comprehensive cancer control resources and data for public health professionals. NIDA supports
several epidemiologic programs designed to gather ongoing data and monitor emerging drug abuse
trends in adolescents and other populations, helping to guide national and global prevention
efforts, drug control, and public health policy. Among the projects is the
Monitoring the Future (MTF) Survey
which has been tracking trends in substance use, attitudes, and beliefs among adolescents and
young adults in the United States since 1975. Data from the 2007 MTF Survey show good news and
continuing areas of concern. For although teen drug use continues to decline—including cigarette
smoking, now at the lowest rate in the survey's history—use of prescription-type drugs is still high,
with more than 15 percent of 12th graders reporting nonmedical use within the past year.
Enhancing the Utility of Data Resources: Tools and Standards
Other efforts aim to enhance the utility of NIH databases. A key element of this work is to
exploit the inherent relationships among information in disparate databases. NIH's
database, for example, is an integrated hub within the Entrez suite of biomedical
information resources. PubChem is the repository for data flowing from the high-throughput
bioassay centers that were established with NIH funding under the
Molecular Libraries Initiative
of the NIH Roadmap. It provides information about the biological activity of small molecules, organized as three linked
databases along with a chemical structure similarity search tool. PubChem's chemical structure and bioassay records are
interlinked with the biomedical literature in PubMed and with three-dimensional protein structure records.
This integration provides many routes by which biomedical researchers may discover the candidate probes
developed by the Molecular Libraries Initiative. A researcher examining a protein sequence record, for example,
may see that a particular protein has been screened, view the active compounds, and examine structure-activity
relationships using PubChem analysis tools. NLM's Discovery Initiative, launched in FY 2006-2007, aims to take
database linking to the next level. The Discovery Initiative will improve the presentation of results from search
queries conducted across a range of NIH databases so that users, who often do not go beyond retrieving the basic
results of a search query, are more likely to be drawn to related information that could lead to serendipitous discoveries,
even if that information resides in another NIH database.
Other efforts relate to the development of standardized nomenclatures and data protocols. Medical terminology can
be difficult to remember and can vary from one laboratory or clinical facility to another. Often there are many
names for a single concept (e.g., cancer of the colon, colonic neoplasm, colon cancer). Standard vocabularies
and ontologies (models of the relationships between concepts) improve information search and retrieval by endowing
systems with the ability to automatically perceive and retrieve information about related terms. As expansion of the
scientific frontiers produces new concepts, terms, and relationships, standard vocabularies must be regularly
revised so that articles and other data can be properly indexed and search engines can find relevant and related
NLM continues to update its Unified Medical Language System (UMLS), which is heavily used in advanced biomedical
research and data mining worldwide. NLM and many other institutions apply UMLS resources in a wide variety of
including information retrieval, natural language processing, creation of patient and research data, and the
development of enterprise-wide vocabulary services. NIH's
database now uses the UMLS to improve the system's ability to retrieve information about clinical trials
related to a user's interests.
UMLS and related NIH programs also contribute to efforts to national efforts to expand the use of electronic
health records to improve the quality and efficiency of health care. Standardized clinical terminology and
coding systems facilitate the exchange of information among care providers, insurers, and patients,
contributing to implementation of an interoperable health information technology infrastructure. NLM
is the government's lead agency for maintaining and disseminating clinical terminology standards. In 2007,
NIH helped to establish the International Health Terminology Standards Development Organization, which is
globally distributing SNOMED CT (Systematized Nomenclature of Medicine?Clinical Terms), a comprehensive
clinical terminology for electronic health records.
Informatics/Computational Biology Initiatives
NIH also has embarked on a number of large-scale initiatives to develop and deploy infrastructure and
tools for storing, sharing, integrating, and analyzing the large volumes of data routinely generated by
In the area of cancer research, for example, NIH has established the cancer Biomedical Informatics Grid
). caBIG is a collaborative
information network for all of NCI's advanced technology and program initiatives, connecting scientists,
practitioners, and patients and enabling the collection, analysis, and sharing of data and knowledge along
the entire research pathway from bench to bedside. Specific biomedical research tools under development by
caBIG include clinical trial management systems, tissue repositories and pathology tools, imaging tools,
and a rich collection of integrative cancer research applications. Patients benefit from caBIG through
systems and services such as BreastCancerTrials.org
(BCT), which was launched in 2006 to match patients' medical case histories to ongoing clinical trials
in the greater San Francisco and Sacramento areas. Created by patients for patients, BCT is an online version
of a caBIG tool called caMatch
which aims to save patients time and energy, while also giving them greater options in seeking clinical trials
that are relevant to their condition.
Other efforts aim to provide the informatics infrastructure to advance basic research and clinical studies across
the spectrum of biomedical sciences. NIH's
Biomedical Informatics Research Network
for example, is a virtual community of shared informatics resources. It includes a data repository that makes research data freely
available for sharing and exchange; data integration tools that allow searching across distributed databases; and tools for data
analysis, management, and collaborative research. The
National Electronics Clinical Trials and Research
(NECTAR) network, a clinical research “network of networks,” is a Roadmap initiative that will provide the informatics
infrastructure for interconnected and inter-operable clinical research networks. NECTAR will allow clinical investigators
to broaden the scope of their research while enhancing efficiency and reducing duplication of efforts by integrating
clinical research networks that currently operate independently of each other. Another Roadmap initiative will create
a national software engineering system through Bioinformatics and Computational Biology initiatives. Through a
computer-based grid, biologists, chemists, physicists, computer scientists, and physicians anywhere in the country
will be able to share and analyze data using a common set of software tools. The National Centers for Biomedical
Computing are a central focus of this effort.
Biomedical Informatics Research and Training
Ensuring continued advances in biomedical informatics resources requires active support of fundamental research
that seeds the further development of new tools, resources, and approaches. It also is critical to generating a
continuous supply of skilled biomedical informatics researchers, information specialists (such as medical librarians),
and life sciences researchers trained in bioinformatics. NIH continues to expand its efforts in bioinformatics research
and training in response to the growing importance of informatics in the biomedical and life sciences
(see section on Research Training).
Several ICs fund informatics research projects within their areas of specialization. However, NLM remains the primary
Federal sponsor of biomedical informatics research, and its extramural grants program supports research on the
characterization, management, and efficient use of data, information, and knowledge in health care and basic biomedical
sciences. Grants funded in FY 2006-2007 explored informatics challenges related to clinical care, biomedical research,
genomics, and public health. NLM's long-range plan, Charting a Course for the 21st Century
, published in September
2006, identifies a number of emerging informatics challenges that will demand continued research and development.
Notable Examples of NIH Activity
Key for Bulleted Items:
E = Supported through Extramural research
I = Supported through Intramural research
O = Other (e.g., policy, planning, and communication)
COE = Supported through a congressionally mandated Center of Excellence program
GPRA Goal = Concerns progress tracked under the Government Performance and Results Act
MEDLINE/PubMed and PubMed Central (PMC):
NIH continued to expand MEDLINE/PubMed as a tool for biomedical
research, clinical medicine and consumer health. Almost 1.3 million citations were added to MEDLINE/PubMed in FY
2006-2007, a 10 percent increase from the previous two-year period. NIH made significant strides in enhancing PMC,
its repository of full-text biomedical journal articles. PMC surpassed the 1 million-articles mark in June 2007,
and, to support NIH policy on public access to NIH-funded research, the NIH Manuscript Submission system was
developed, enabling NIH grantees to deposit manuscripts into PMC. To foster international cooperation on preservation
and access to biomedical literature, NIH made PMC software available to archiving organizations outside the United
States and worked with the Wellcome Trust and other major United Kingdom research funders in the to establish a
UKPMC service. Five other countries plan to establish PMC sites.
MedlinePlus/MedlinePlus en Español:
NIH employed new methods to increase awareness of its MedlinePlus
databases. Weekly podcasts by NLM's Director were initiated to provide timely reports on health news; NIH
MedlinePlus The Magazine
was rolled out at a press event on Capitol Hill attended by members of Congress
and guest celebrity Mary Tyler Moore, featured on the cover. The magazine is distributed free of charge to
40,000 physician offices and has covered stories on cancer, diabetes, and heart attack. NIH expanded the
content and features of the English and Spanish MedlinePlus Web sites and the associated GoLocal sites that
provide information on local health resources for approximately one-third of the U.S. population. MedlinePlus
was one of two U.S. winners of the 2005 Award at the World Summit on the Information Society.
TOXicology Data NETwork (TOXNET):
- For more information, see https://www.medlineplus.gov
- This example also appears in Chapter 3: Health Communication and Information Campaigns and Clearinghouses.
- (I) (NLM)
TOXNET is a cluster of more than 10 databases covering toxicology,
hazardous chemicals, environmental health, and related topics. It is a primary reference for toxicologists,
poison control centers, public health administrators, physicians, and other environmental health professionals.
In 2006, the Hazardous Substances Data Bank, which contains comprehensive information on more than 5,000
substances, was expanded to include a general record for
and a series of specific radionuclide records. In 2007, LactMed, a peer-reviewed and fully referenced database
of drugs to which breast-feeding mothers may be exposed, was added to TOXNET.
National NeuroAids Tissue Consortium (NNTC):
The NNTC is a repository of brain tissue and fluids from
highly characterized HIV+ individuals. Established as a resource for the research community, the NNTC includes
information from over 2,000 individuals, including approximately 641 brains, thousands of plasma and cerebrospinal
fluid samples, and additional organs and nerves of interest.
Established in 2000 in response to congressional mandate (Pub. L. No. 105-115),
ClinicalTrials.gov has grown to become the largest clinical trial registry in the world with information
on clinical research studies for hundreds of diseases and conditions conducted in 148 countries. At the
end of September 2007, it contained more than 47,000 registered trials—more than double the number of
entries 2 years earlier. Legislation enacted in September 2007, the Food and Drug Administration Amendments
Act of 2007 (Pub. L. No. 110-85), expanded the scope of trials to be registered with ClinicalTrials.gov and
the registration information to be provided. It also mandates the inclusion of specified results information
beginning in September 2008.
Influenza Virus Resource:
This database of more than 40,000 influenza virus sequences allows researchers
around the world to compare different virus strains, identify genetic factors that determine the virulence of
virus strains, and look for new therapeutic, diagnostic, and vaccine targets. The resource was developed by
NCBI using data obtained from NCBI's Influenza Virus Sequence Database and from NIAID's Influenza Genome
Sequencing Project, which has contributed sequences of the complete genomes from over 2,500 influenza samples.
In FY 2006 more than 11,000 influenza virus sequences were entered into the database, and new search and
annotation tools were added to assist researchers in their analyses.
PubChem provides information on the biological activities of small molecules.
It is a component of NIH's Molecular Libraries Roadmap Initiative. By the end of 2007, PubChem
contained information on more than 38 million substances, 18 million compounds, and 710 bioassays.
Databases for Cervical Cancer Research:
NIH has developed data analysis and image recognition
tools for studying biomedical images of human papillomavirus (HPV) infection and cervical neoplasia.
Image data include 100,000 cervicographs (high-definition cervical photograph), Pap test, and histology
images. Tools allow the exploration of visual aspects of HPV and cervical cancer for research, training,
Genomic Information Systems
Database of Genotype and Phenotype (dbGaP):
Research on the connection between genetics
and human health and disease has grown exponentially since completion of the Human Genome Project
in 2003, generating high volumes of data. Building on its established research resources in
genetics, genomics and other scientific data, NIH established dbGaP to house this growing body
of information, particularly the results of GWAS, which examine genetic data of subjects with
and without a disease or specific trait to identify potentially causative genes. By the end of
2007, dbGaP included results from more than a dozen GWAS, including genetic analyses added to
the landmark Framingham Heart Study and trials conducted under the Genetic Association Information
Network. dbGaP is to become the central repository for many NIH-funded GWAS in order to provide for
rapid and widespread distribution of such data to researchers and accelerate the advance of
Genome-Wide Association Studies (GWAS) and Database of Genotype and Phenotype (dbGaP)
- For more information, see https://view.ncbi.nlm.nih.gov/dbgap
- This example also appears in Chapter 3: Epidemiological and Longitudinal Studies and Chapter 3: Genomics.
- (I) (NLM)
: In December 2006,
NIH released the initial dbGaP dataset using genome-wide association data from the Age-Related Eye Diseases
Study (AREDS), a landmark study of the clinical course of age-related macular degeneration (AMD) and cataracts.
AREDS documents, protocols, and aggregated data are made available with no restrictions. In order to protect
patient confidentiality, de-identified individual-level patient characteristics and family data are accessible
only by authorized investigators. Correlating phenotype and genotype data provides information about the genetic
and environmental interactions involved in a disease process or condition, which is critical for better
understanding complex diseases and developing new diagnostic methods and treatments. Using these data, recent
studies have linked two genes with progression to advanced AMD. After controlling for other factors, certain
forms of the genes increased risk of AMD progression 2.6- to 4.1-fold; smoking and body weight further
increased risk with these gene variants.
NIMH Genetics Repository:
Over the last 9 years, NIMH has built the infrastructure for large-scale genetics
studies through the NIMH Human Genetics Initiative. Through this Initiative, NIMH established a repository of DNA,
cell cultures, and clinical data-serving as a national resource for researchers studying the genetics of complex
NINDS Human Genetics Repository:
- For more information, see https://nimhgenetics.org/
- This example also appears in Chapter 3: Genomics and Chapter 2: Neuroscience and Disorders of the Nervous System.
- (E) (NIMH)
In 2003, NINDS established this Repository to collect, store, characterize,
and distribute DNA samples and cell lines and standardized clinical data for the research community. By June 2007,
the repository held material from 16,683 subjects, including stroke (4,363), epilepsy (1,065), Parkinson's disease
(3,585), motor neuron diseases such as ALS (2,445), and control samples (4,767). The ethnically diverse collection
represents populations from the United States and several other countries. Investigators have submitted or published
more than 50 scientific articles based on data from this resource, and technological advances allowing
“whole genome screening” for disease genes have also enhanced its value.
Candidate Gene-Association Resource:
Over the years, NHLBI has supported a number of major population studies
that have collected extensive data on cardiovascular disease and its risk factors and manifestations. To increase the
utility of the data for conducting genetic association studies, NIH initiated the Candidate Gene Association Resource
program in FY 2006. This new resource will have the capacity to perform high-throughput genotyping for up to 50,000
subjects in cohort studies that have stored samples and data available on a wide array of characteristics (phenotypes)
associated with heart, lung, blood, and sleep disorders. The linked genotype-phenotype data will form an invaluable
resource for investigators seeking to identify genetic variants related to those disorders.
Alzheimer's Disease (AD) Genetics Initiative and Data Storage:
Only one of the four validated AD genes, APOE,
has been definitively linked with the more common late-onset form of the disease. A fifth gene, SORL1, has recently
been linked with late-onset Alzheimer's disease (LOAD) in some studies. The goal of the AD Genetics Initiative is to
develop the resources necessary for identifying the LOAD risk factor genes and the interactions of genes with the
environment. In FY 2006, NIH achieved its goal to recruit 1,000 families with two or more siblings living with AD
through an unprecedented alliance of AD Centers, researchers, and outreach with the Alzheimer's Association. To
facilitate access by qualified investigators, all genetic data derived from NIH-funded studies on LOAD genetics
are deposited at a central data storage site at Washington University in St. Louis, another NIH-approved site,
or both. Discovery of risk factor genes will help illuminate the underlying disease processes of AD, open up
novel areas of research, and identify new targets for drug therapy.
Autoimmune Diseases and Genetics:
- For more information, see https://www.niageneticsdata.org/
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System.
- (E/I) (NIA)
With the advancement of genomic science, more information has been gained
about the genetic component of autoimmune diseases. Susceptibility genes have been identified for rheumatoid
arthritis, lupus, psoriasis, and alopecia areata. Understanding the genetic influence of these diseases
provides essential information for the design of new therapies.
- Kumar KR, et al. Science 2006;312:1665-9, PMID: 16778059
- Nair RP, et al. Am J Hum Genet 2006;78:827-51, PMID: 16642438
- Haas CS, et al. Arthritis Rheum 2006;54:2047-60, PMID: 16804865
- Martinez-Mir A, et al. Am J Hum Genet 2007;80:316-28, PMID: 17236136
- For more information, see
- This example also appears in Chapter 2: Autoimmune Diseases.
- (E) (NIAMS, NCRR, NHLBI, NIAID, NIMH)
Disease Registries and Surveillance Systems
Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS):
In a joint effort,
NHLBI, the Center for Medicare & Medicaid Services, and the U.S. Food and Drug Administration created
INTERMACS, a national registry for patients who are receiving mechanical circulatory support device
therapy to treat advanced heart failure. Data from INTERMACS are expected to improve patient evaluation
and management, aid in the development of safer, more effective devices, and enhance research.
Resuscitation Outcomes Consortium:
- For more information, see https://www.uab.edu/ctsresearch/mcsd/
- This example also appears in Chapter 2: Chronic Diseases and Organ Systems and Chapter 3: Technology Development.
- (E) (NHLBI)
Recognizing the critical importance of early intervention for
victims of cardiopulmonary arrest and traumatic injury, in FY 2004 NIH and its U.S. and Canadian partners
initiated the Resuscitation Outcomes Consortium, a large-scale network to conduct clinical trials of
promising approaches to improving outcomes. During FY 2006-2007, two Consortium clinical trials began
enrolling patients—one to compare the efficacy of three fluids for initial resuscitation of hypotensive
or brain-injured patients and the other to test two strategies for increasing blood flow during
cardiopulmonary resuscitation. The Consortium also established a pre-hospital Cardiac Arrest and Trauma
Registry across the United States and Canada. In addition, emergency medicine fellowship training programs
established at several study sites are enhancing training in resuscitation medicine.
A Look at Drug Abuse Trends: Local to International:
- For more information, see https://roc.uwctc.org/
- This example also appears in Chapter 3: Clinical and Translational Research.
- (E) (NHLBI, NINDS)
Several major systems of data collection are
helping to identify substance abuse trends locally, nationally, and internationally: Monitoring the Future
Survey (MTF), the Community Epidemiology Work Group (CEWG), and the Border Epidemiology Work Group (BEWG).
All help to surface emerging drug abuse trends among adolescents and other populations, and guide responsive
national and global prevention efforts. The MTF project, begun in 1975, has many purposes, the primary one
being to track trends in substance use, attitudes, and beliefs among adolescents and young adults. The survey
findings are also used by the President's Office of National Drug Control Policy to monitor progress towards
national health goals. The MTF project includes both cross-sectional and longitudinal formats—the former
given annually to 8th, 10th, and 12th graders to see how answers change over time, and the latter given
biennially, or every 2 years (until age 30, then every 5 years) to follow up on a randomly selected sample
from each senior class. CEWG, established in 1976, provides both national and international information
about drug abuse trends through a network of researchers from different geographic areas. Regular meetings
feature presentations on selected topics, as well as those offering international perspectives on drug abuse
patterns and trends. A recently established Border Epidemiology Work Group represents a collaboration of
researchers from both sides of the U.S.-Mexico border. Of special interest are drug abuse patterns and
problems in geographically proximal sister cities/areas. Development of a Latin American Epidemiology
Network is under way. NIH has also provided technical consultation for the planning and establishment
of an Asian multi-city epidemiological network on drug abuse.
Parkinson's Disease Registry:
NIEHS has begun to address the need for more precise data on the
incidence and prevalence of Parkinson's disease through support of a Parkinson's disease registry in
the State of California, where the large and diverse population, coupled with the wide range of exposures
that exist through agriculture and other activities, provide a unique opportunity to investigate
disease-environment links. The United States does not have a national health registry to supply data
on Parkinson's disease, so estimates are based on sampling by individual studies in specific locales.
The Parkinson's registry in California will allow us to base national estimates on a registry drawing
upon a cross-section of the population in our most populous state.
Surveillance, Epidemiology, and End Results (SEER) Program and Software Analysis Tools:
program is an authoritative source of information on cancer incidence and survival in U.S. publications,
such as the Annual Report to the Nation on the Status of Cancer, or interpretation of recent declines
in breast cancer incidence to inform the public, researchers, Federal and private agencies, and Congress
on national cancer rates and trends. SEER is the only comprehensive source of population-based information
in the United States that includes stage of cancer at the time of diagnosis, patient survival, and treatment.
Linkage with Medicare and other Federal databases yields information sources that are used routinely to answer
major questions on quality, cost, and variability of cancer care as well as differences by racial and ethnic
populations. SEER currently collects and publishes data from approximately 26 percent of the U.S. population.
The team is developing computer applications to unify cancer registration systems, to analyze and disseminate
data, and to provide limited access to the public file. SEER is considered the standard for quality among
cancer registries around the world.
Gene Expression Changes in Facioscapulohumeral Muscular Dystrophy (FSHD):
Results from a genome-wide
scan of skeletal muscle biopsies suggest a link between eye blood vessel
defects and muscle defects that characterize FSHD. Patient subjects were recruited from the National Registry for Myotonic Dystrophy and FSHD Patients and Family Members.
Genetic Susceptibility for Alopecia Areata:
Scientists supported by NIH have identified loci on four
chromosomes that appear to play a role in the development of alopecia areata, an autoimmune disease
characterized by hair loss that can affect the whole scalp or, in rarer cases, the entire body. Many U.S.
families recruited for the study were identified through the Alopecia Areata Registry.
Enhancing the Utility of Data Resources: Tools and Standards
A Clearinghouse for Neuroimaging Informatics Tools and Resources:
NIH understands that researchers
seeking neuroimaging analysis software tools need a convenient way to find and compare useful software.
Indeed, the best or most suitable neuroimaging analysis technologies for research may be hidden in someone's
laboratory or some obscure corner of cyberspace. NIH is creating a Neuroimaging Informatics Tools and
Resources Clearinghouse. The 14 NIH ICs that participate in the Neuroscience Blueprint have supported the
development of sophisticated, high-quality neuroimaging informatics tools and resources. The clearinghouse
is intended to facilitate the dissemination of those tools and resources and promote their adoption within
the extended neuroimaging community. A contract has been awarded to create the clearinghouse infrastructure.
The infrastructure will include a Web site that will provide not only access to tools and resources, but also
ongoing opportunities for public comment in order to guide future development and enhancement of the tools.
In addition to the contract award, grant awards are being made to individual extramural scientists to enable
them to render their tools more suitable for this initiative. The awards will fund the enhancement of tools
to make them easier to use, more broadly applicable, or more compatible with other existing tools.
The clearinghouse was released to the public in October 2007.
Health IT Standards:
- For more information, see https://www.nitrc.org/
- For more information, see https://neuroscienceblueprint.nih.gov/
- This example also appears in Chapter 2: Neuroscience and Disorders of the Nervous System
- (E) (NIBIB, NCCAM, NCRR, NEI, NIA, NIAAA, NICHD, NIDA, NIDCD, NIDCR, NIEHS, NIGMS, NIMH, NINDS, NINR, OBSSR)
NIH's UMLS Metathesaurus is a distribution mechanism for standard code sets and
vocabularies used in health data systems. NIH supports, develops, or licenses key health terminologies to enable
their free use in U.S. electronic health record systems. In 2007, NIH helped to establish the International
Health Terminology Standards Development Organization to promote more cost-effective maintenance and
international adoption of the SNOMED CT clinical terminology. NIH supports ongoing development and
distribution of the LOINC nomenclature for laboratory tests and patient observations and produces RxNorm,
a standard clinical drug vocabulary. Another NIH resource, the Daily Med, is an official distribution
mechanism for FDA-approved packaging information (drug label inserts) that links to other sources of drug
information, including NIH's MedlinePlus, ClinicalTrials.gov, and PubMed. More than 60,000 people subscribe
to its RSS data feeds.
UMLS Knowledge Sources:
NIH's Unified Medical Language System® (UMLS) aims to facilitate the
development of computer systems that behave as if they understand the meaning of biomedical and health
terms. The UMLS tools underpin many production information retrieval systems at NLM and elsewhere and
are heavily used in advanced research in biomedical natural language processing and data-mining across
the country and around the world. The most recent UMLS Metathesaurus contains more than 1.3 million
biomedical concepts and 6.4 million concept names from more than 100 source vocabularies.
Radiation Event Medical Management (REMM):
As a part of an effort to improve public health
emergency preparedness and response, NIH and the HHS Office of the Assistant Secretary for Preparedness
and Response announced in 2007 a new downloadable online diagnostic and treatment toolkit to guide health
care providers during a mass casualty radiation event. The REMM toolkit includes easy-to-follow procedures
for diagnosis and management of radiation contamination and exposure, guidance for the use of radiation
medical countermeasures, and a variety of other features to facilitate medical responses to radiation
Patient-Reported Outcomes Measurement Information System (PROMIS):
- For more information, see https://remm.nlm.gov
- This example also appears in Chapter 2: Infectious Diseases and Biodefense.
- (I) (NLM)
This NIH Roadmap initiative is developing
ways to measure symptoms—such as pain, fatigue, physical functioning, social role participation, and emotional
distress—that influence quality of life across numerous chronic diseases.
The Cancer Control P.L.A.N.E.T:
This Web portal is a collaboration aimed at providing access to data and
resources that can help cancer control planners, health educators, program staff, and researchers design,
implement, and evaluate evidence-based cancer control programs. It assists local programs with the resources
that help them determine cancer risk and the cancer burden within their State. It also helps States identify
potential partners and provides online resources for interpreting research findings and recommendations, and
accessing products and guidelines for planning and evaluation.
Informatics/Computational Biology Initiatives
Biomedical Informatics Research Network (BIRN):
Modern biomedical research generates vast amounts of
diverse and complex data. Increasingly, these data are acquired in digital form, allowing sophisticated and
powerful computational and informatics tools to help scientists organize, store, query, mine, analyze, view,
and, in general, make better use and sense of their data. Moreover, the digital form of these data and tools
makes it possible for them to be easily and widely shared across the research community at large. NIH has
supported development of the BIRN infrastructure to share data and tools by federating new software tools or
using the infrastructure to federate significant datasets. BIRN fosters large-scale collaborations by utilizing
the capabilities of the emerging national cyberinfrastructure. The project includes a Coordinating Center at the
University of California, San Diego, which serves the critical task of developing, deploying, and maintaining key
infrastructure components, including high-bandwidth connectivity, grid-based security, file management and
computational services, techniques to federate databases, and shared visualization and analysis environments.
National Database for Autism Research (NDAR):
- For more information, see www.nbirn.net
- This example also appears in Chapter 3: Technology Development.
- (E) (NCRR)
The NDAR is a collaborative biomedical informatics system
being created by NIH to provide a national resource to support and accelerate research in autism.
National Centers for Biomedical Computing (NCBCs):
- For more information, see https://ndar.nih.gov
- This example also appears in Chapter 2: Life Stages, Human Development, and Rehabilitation and Chapter 2: Neuroscience and Disorders of the Nervous System.
- (E/I) (NIMH, CIT, NICHD, NIDCD, NIEHS, NINDS)
The NIH Roadmap Bioinformatics and Computational
Biology initiative provides a networked national effort to build computational tools and infrastructure for
biomedical computing. The centers are devoted to all facets of biomedical computing, from basic research in
computational science to providing the tools and resources that biomedical, clinical, and behavioral
researchers need to do their work. The seven centers currently supported by the NIH Roadmap have made
substantial progress in software development, data resources, and scientific ontologies. These advances
are currently being used by the research community for studying a broad range of biological problems
including cerebral palsy, autism, diabetes, asthma, Alzheimer's disease, Huntington's disease, schizophrenia,
bipolar disorder, HIV/AIDS, and prostate cancer. The long-term goal of the initiative is to create a national
software engineering system that will enable biomedical and clinical researchers to share and analyze data
using a common set of software tools.
Biomedical Informatics Research and Training
The Discovery Initiative aims to maximize the utility of NIH biomedical data
resources by better exploiting their inter-linkages. For example, a PubChem record on a chemical structure
might link to records for similar proteins, related protein structures, and relevant journal articles. Such
linkages provide users with tremendous opportunities for exploration and scientific discovery but are currently
underutilized. The Discovery Initiative aims to improve the retrieval and presentation of results so that
users are more readily drawn to related data that could lead to serendipitous discoveries.
Informatics Training for Global Health:
Information technology is required in almost all research programs,
both to access the vast information resources available internationally and to apply to research design and analysis.
This program is intended to increase the capacity of developing country scientists and medical professionals to
design, access, and use modern information technology in support of health sciences research. Specifically, this
program supports innovative training programs for developing country biomedical and behavioral scientists and
engineers, clinicians, librarians, and other health professionals to increase their capacity to access, manage,
analyze, interpret, manipulate, model, display, and share biomedical information electronically. Among other skills,
this will increase their ability to conduct multisite clinical trials and international disease surveillance and prevention programs.
Informatics Research Training Programs:
To address the national need for computational scientists competent in
biology and medicine, NLM reviewed its University Informatics Research Training Programs and issued a new call for
applications. Curricula were updated to reflect current computing needs in clinical translational research and
public health. Eighteen 5-year grants, totaling more than $75 million, for research training in biomedical
informatics, were awarded in 2006. Approximately 270 trainees are currently enrolled in these programs.