Cheminformatics and Bioinformatics @ NIH
Susan K. Gregurick, Ph.D. Division DirectorBiomedical Technology, Bioinformatics and Computational Biology
Cheminformatics-2017
“Science in pursuit of fundamental knowledge about the nature and behavior of living systemsand the application of that knowledge to extend healthy life and reduce illness and disability.”
...
The National Institutes of HealthThe Nation’s Steward of Medical & Behavioral Research
Cheminformatics-2017
Understanding the Dual Nature of NIH
NIH supports institutions & people(Extramural Research)
• >2,500 institutions• >400,000 scientists & research
personnel• Approx. 70,000 applications and 40,000
awards annually• Approx. 81% of the NIH budget
NIH is an institution(Intramural Research)
• Approx. 6,000 scientists• Approx. 11%
of NIH’s budget
Source: report.NIH.gov - awards by location, 10/5/2017
Alaska
Hawaii
Cheminformatics-2017 4
National Institutes of Health
National Instituteon Alcohol Abuseand Alcoholism
National Instituteof Arthritis andMusculoskeletal
and Skin Diseases
National CancerInstitute
National Instituteon Aging
National Instituteof Child Health
and HumanDevelopment
National Instituteof Allergy and
Infectious Diseases
National Instituteof Diabetes andDigestive and
Kidney Diseases
National Instituteof Dental andCraniofacial
Research
National Instituteon Drug Abuse
National Instituteof EnvironmentalHealth Sciences
National Institute onDeafness and Other
CommunicationDisorders
National EyeInstitute
National HumanGenome Research
Institute
National Heart,Lung, and Blood
Institute
National Instituteof Mental Health
National Instituteof NeurologicalDisorders and
Stroke
National Instituteof General
Medical SciencesNational Institute
of Nursing Research
National Libraryof Medicine
National Centerfor Complementary
and AlternativeMedicine
FogartyInternational
Center
National Centerfor AdvancingTranslational
Sciences
National Instituteof Biomedical Imaging and
Bioengineering
NIHClinical Center
Centerfor Information
Technology
Center for Scientific
Review
National Center on Minority Health
and Health Disparities
Office of the Director
No funding authority
Cheminformatics-2017
NIH Mission
To seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability.
To seek fundamental knowledge about the nature and behavior of living systems and the application of that knowledge to enhance health, lengthen life, and reduce illness and disability
FY2018 Priorities:1. Fundamental Science Enhanced by Technological Advances
2. Treatments and Cures
3. Health Promotion and Disease Prevention
4. Enhancing Stewardship
Cheminformatics-20176
Brain Research through Advancing Innovative Neurotechnologies
Cheminformatics-2017
7
• Researchers created a 3-D model of the interactions between developing brain regions—in a dish.
• Using the model, the team looked at how mutations that cause Timothy syndrome affect brain development and discovered a defect in how neurons migrate between regions.
• The results suggest a way to study personalized brain development and disease.
NIH BRAIN Initiative Breakthroughs
After spheroids representing two different brain regions fuse in a dish, neurons from one spheroid (green) migrate into the other and forge connections with the neurons there.Pasca lab, Stanford University
Cheminformatics-2017
All of Us
Cheminformatics-2017
9
Rheumatoid arthritis mechanisms may vary by joint
•An epigenomic analysis of rheumatoid arthritis in knee and hip joints revealed unique patterns that suggest disease mechanisms may differ from joint to joint.
•The findings could open the door to development of more effective, personalized therapies for rheumatoid arthritis.
A research team led by Drs. Gary S. Firestein and Wei Wang at the University of California, San Diego,
study fibroblast-like synoviocytes (FLS), a type of cell that lines joints and contributes to joint destruction
in rheumatoid arthritis
Cheminformatics-2017
Support for developing new cutting-edge techniques to advances treatment for sickle cell disease
Focus on Cancer Immunotherapy to discover new immune targets and evaluate new immune-based approaches
Treatments and Cures
Intervening in the Opioid Epidemic to:
• prevent opioid misuse and addiction• develop new and improved treatments for opioid addiction • improving the deployment of evidence based strategies for combatting overdose• preventing and treating addiction • develop more effective treatments for pain with reduced potential for addiction and
misuse
Cheminformatics-2017
Designing more effective opioids
•Researchers used computer simulations to screen millions of molecules for opioid-like pain-relieving properties.
•The analyses allowed scientists to create a molecule that effectively alleviates pain in mice, but with fewer side effects than the opioid morphine.
A computer model of the synthesized pain relieving compound PZM21 (blue) docked with the
mu opioid receptor (grey).Dr. Bryan Roth, University of North Carolina
Cheminformatics-201712
• Coordinate access to and analysis of the many types of biological and behavioral ‘big data’ being generated by biomedical scientists
• Develop innovative and transformative computational approaches, tools, and infrastructures to make ‘big data’ and data science a prominent component of biomedical research
• Enable data sharing and utilization through the development of a new shared, interoperable cloud computing environment: the ‘Commons’
Data Science @ NIH
Cheminformatics-2017
Making FAIR a Reality: NIH Data Commons Pilot Phase
1). Develop methods that support Global Unique Identifiers (GUID) for FAIR Biomedical Digital Objects2). Promote indexing metadata through FAIR compliant APIs.
1). Create Workspaces for Computations
2). Develop Scientific Use Cases
1). Develop cloud agnostic platforms
2). Develop open API standards
1). Develop FAIR guidelines and metrics2). Develop approaches to address data ethics, privacy and security
Cheminformatics-2017
Data Commons Pilot Phase Consortium (DCPPC)
Compute Platform: Cloud
Services: APIs, Containers, GUIDs, Indexing, Search, Auth
Software: Services & Tools
Scientific analysis tools/workflows
Data
“Reference” Data SetsTOPMed, GTEx, MODs
FAIR
App store/User Interface/Portal/Workspace
Key Capabilities (KC)
1. Development and Implementation Plan for Community Supported FAIR Guidelines and Metrics
2. Global Unique Identifiers (GUID) for FAIR Biomedical Digital Objects
3. Open Standard APIs4. Cloud Agnostic Architecture and Frameworks 5. Workspaces for Computation6. Research Ethics, Privacy, and Security (AUTH)7. Indexing and Search 8. Scientific Use cases9. Training, Outreach, Coordination
Cheminformatics-2017
Targeted Data Sets in Pilot Phase:
• TOPMed• Gtex• MODs
NIH Data Commons Pilot Phase
June July Aug
Awards finalized
Sept 12
Review of Applications
Aug 21-23
Invitation to Submit
Applications
Jul 12
Review of LOIs
Jul 7
LOIs DueJune 30
OTA Released
Jun 15
Kick off meeting
Review
Award Negotiations
Consortia Begins
Sept Mar 2018Oct
180 daysPlans and
prototypesSubmission of Applications
Jul 31
Cheminformatics-2017
Cheminformatics and Medicinal Chemistry @ NIH
16
• HTS for inhibitors• Virtual Screening and
Optimization• Medicinal and
Synthetic Chemistry• Computational
Synthetic Chemistry• Natural Products
inspired Therapeutics
Cheminformatics-2017
NIH Funding in Cheminformatics
17
0
500000
1000000
1500000
2000000
2500000
3000000
3500000
4000000
4500000
NIGMS NIAID NINDS NCI NIMH NIAMS NIDA NIA NIEHS NHLBI NCATS NIDCD NICHD
Total Funding
Total Funding $21M
NIDA CENTER OF EXCELLENCE OF COMPUTATIONAL DRUG ABUSE RESEARCH (CDAR)
Cheminformatics-201718
Deep Learning and Cheminformatics
• Most scientists familiar with applications of deep learning to problems of image, speech, and text analysis.
• However, fewer are familiar with applying deep learning techniques to molecular data.
• Recently there has been an upswing in research andindustry interest in applying deep neural networks to predicting things like drug solubility, toxicity and maybe even synthetic routes.
Cheminformatics-2017
19
• PA-17-032
• This funding opportunity announcement encourages the use of existing and the development of novel computational approaches to identify drugs or drug combinations currently used for other conditions with potential to be efficacious in AD and AD-related dementias.
• POC: Suzana Petanceska, Ph.D. (NIA)
Translational Bioinformatics: Advanced Drug Repositioning for Therapy Development in Alzheimer’s (R01)
Cheminformatics-2017
20
• PA-17-330 (R01)
• Stimulate research to identify new and novel targets and mechanisms involved in tumor immune evasion
• A specific focus of this FOA is to encourage cross disciplinary collaborations between immunologists, cell biologists, medicinal chemists, pharmacologists, and molecular biologists
• POC: R. Allan Mufson, Ph.D (NCI)
Using Small Molecules and Molecular Genetics to Identify Novel Targets and Mechanisms Contributing to Tumor Immune Evasion
Cheminformatics-201721
Chemistry Science Track Award for Rapid Transition (C/START)(R03)
• PAR-16-383
• The National Institute on Drug Abuse (NIDA) seeks to facilitate the entry of new/early stage investigators (ESIs) into substance use disorder (SUD) research.
• ESIs are invited to submit applications for small scale, innovative chemical/pharmacological pilot research projects
• Enable an ESI the opportunity to gather preliminary data in support of subsequent research grants
• POC: Kristopher Bough, PhD (NIDA)
Cheminformatics-2017
Initiatives that Support Computational and Mathematical Sciences
• Biomedical Information Science and Technology Initiative (BISTI)Promote the optimal use of computer science and technology to address problems in biology and medicine by fostering collaborations and interdisciplinary initiatives (bisti.nih.gov)
• Big Data to Knowledge Initiative (BD2K)Develop new approaches, standards, methods, tools, software and competencies that will enhance the use of biomedical data & support initial efforts toward making data sets “FAIR” Findable, Accessible, Interoperable, and Reusable(datascience.nih.gov/bd2k)
• Interagency Modeling and Analysis Group (IMAG)Provide an open forum for communication among government representatives for trans-agency activities that have a broad impact in science (imagwiki.nibib.nih.gov)
• NSF/NIH Joint program in Mathematical Biology
Bring mathematics and statistics into the core of biological and biomedical research and to broaden the use of innovative mathematics in understanding life processes.
Cheminformatics-201723
Cheminformatics-201724
• Supports basic research that increases understanding of biological processes and lays the foundation for advances in disease diagnosis, treatment and prevention
• Funds scientists to investigate how living systems work at a range of levels, from molecules and cells to tissues, whole organisms and populations
• Supports research in certain clinical areas, primarily those that affect multiple organ systems
• Provides leadership in o Training the next generation of scientistso Enhancing the diversity of the scientific workforceo Developing research capacities throughout the country
NIGMS Mission
Cheminformatics-2017
• Division of Biomedical Technology, Bioinformatics, and Computational Biology
• Division of Cell Biology and Biophysics
• Division of Genetics and Developmental Biology
• Division of Pharmacology, Physiology,
and Biological Chemistry
• Division of Training, Workforce
Development, and Diversity
• Center for Research Capacity Building
25
NIGMS Scientific Components
Cheminformatics-20172626
Investigator Initiated Research @ NIGMS
Maximizing Investigators' Research Award (MIRA) PAR-17-094
Provide a single grant for sustained research support to investigators to:
o Enhance ability to take on ambitious projects
o Increase flexibility in research directions
o Increase research time and productivity
o Enable mentoring in a stable environment
Cheminformatics-20172727
Collaborative Research @ NIGMS
A mechanism to support research that cannot be accomplished by individual researchers PAR-17-094
o Budget $500K - $1.5M D.C. for research activities
o Address research questions of significant complexity, scope, and biomedical impact
o Foster highly integrated and collaborative research teams
o Strengthen scientific communities and advance scientific problems through coordinated research effort
o Increase ESI exposure to team-based research, through pilot studies
Cheminformatics-201728
NIGMS Research Funding
https://www.nigms.nih.gov/research
Cheminformatics-2017
Initiates grant application
NIHGrant Proposal
Researcher
Assess programsSecond level of review
InstituteNational Advisory
Councils
Evaluates scientific merit of grant proposal
Scientific Review Panel
Institute Director
Makes final decisionAllocates funds
29
Understanding the Funding Process
Cheminformatics-201730
NIGMS Research Support
• More than 3,000 investigators and 4,500 research grants
• Over 11% of the grants funded by NIH
• Emphasis is on investigator-initiated research
Success Rates
Cheminformatics-201731
Keep in Touch!
https://loop.nigms.nih.gov
@NIGMS
@NIGMSgenes
Thank You!
Cheminformatics-2017
Initiatives that Support Bioinformatics and Computational Biology
33
• Biomedical Information Science and Technology Initiative (BISTI)Promote the optimal use of computer science and technology to address problems in biology and medicine by fostering collaborations and interdisciplinary initiatives
• Big Data to Knowledge Initiative (BD2K)Develop new approaches, standards, methods, tools, software and competencies that will enhance the use of biomedical Big Data by supporting research, implementation and training in the data sciences
• Interagency Modeling and Analysis Group (IMAG)Provide an open forum for communication among government representatives for trans-agency activities that have a broad impact in science