1. CIIPro: An online
cheminformatics portal for large
scale chemical data analysis
Daniel P Russo,1 Wenyi Wang,1 Daniel Pinolini,1 Marlene T Kim,1,2 and
Hao Zhu1, 2
Zhu Research Group
1The Rutgers Center for Computational and Integrative Biology, Camden, New Jersey 08102;
2Department of Chemistry, Rutgers University, Camden, New Jersey 08102;
2. Outline
• Motivation: Current state of toxicology
• High throughput screening
• In vitro-in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro-in vivo profiling
• CIIP Nearest Neighbor: Using CIIPro to find biological
nearest neighbors
• Demonstration
• The future of CIIPro
• Motivation: Current state of toxicology
• High throughput screening
• In vitro-in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro-in vivo profiling
• CIIP Nearest Neighbor: Using CIIPro to find biological
nearest neighbors
• Demonstration
• The future of CIIPro
2
3. Current State of Toxicology: Traditional toxicology testing
CIIPro: Current State of Toxicology 3
$20M
Cancer
ReproTox
DevTox
NeuroTox
PulmonaryTox
ImmunoTox
Chemical
Slide courtesy of Dr. Richard Judson, U.S. EPA
4. Current State of Toxicology: High throughput screening
CIIPro: Current State of Toxicology 4Collins, F. S., Gray, G. M. & Bucher, J. R. Transforming Environmental Health
Protection. Science 319, 906–907 (2008).
5. Current State of Toxicology: What can we learn?
CIIPro: Current State of Toxicology 5
Zhu, H. et al. Big data in chemical toxicity research: the use of high-throughput screening
assays to identify potential toxicants. Chem. Res. Toxicol. 27, 1643–1651 (2014).
6. Current State of Toxicology: From databases to researchers
CIIPro: Current State of Toxicology 6
Growing pool
of in vitro
data
Chem. Res. Tox. 2014; (27) 1643-1651
7. CIIPro: An online cheminformatics portal
CIIPro: An online Cheminformatics portal 7
8. Outline
• Motivation: Current state of toxicology
• High throughput screening
• In vitro-in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro-in vivo profiling
• CIIP Nearest Neighbor: Using CIIPro to find biological
nearest neighbors
• Demonstration
• The future of CIIPro
8
9. Target
Compounds
I. Create Optimized
Biological
Profile
II a. Calculate
Biological Similarity
II b. Calculate
Biological Nearest
Neighbors
II c. Evaluate
Biological Activity
Using Biological
Nearest Neighbors
I. CIIProfiler
II. CIIP BioNN
The four steps of CIIPro
10. Outline
• Motivation: Current state of toxicology
• High throughput screening
• In vitro-in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro-in vivo profiling
• CIIP Nearest Neighbor: Using CIIPro to find biological nearest
neighbors
• Demonstration
• The future of CIIPro
10
I. Create a biological profile
12. Outline
• Motivation: Current state of toxicology
• High throughput screening
• In vitro in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro, in vivo profiling
• CIIP Nearest Neighbor: Using CIIPro to find biological
nearest neighbors
• Demonstration
• The future of CIIPro
12
II a. Use biological profile to
calculate biological similarity
II b. Use biological similarity create
biological nearest neighbors
II c. Use biological nearest
neighbors to evaluate biological
activity
14. Outline
• Motivation: Current state of toxicology
• High throughput screening
• In vitro in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro, in vivo profiling
• CIIP Predictor: Using CIIPro to create robust toxicity models
• Demonstration
• The future of CIIPro
14
15. Demonstration
Demonstration 15
*Wang W., Kim M. T., Sedykh A., and Zhu, H. Developing Enhanced Blood–Brain Barrier Permeability
Models: Integrating External Bio-Assay Data in QSAR Modeling. Pharm Res 32, 3055–3065 (2015).
Blood Brain Barrier
Dataset* Overview
114
Barrier
Permeable
Compounds
1
114
Barrier
Impermeable
Compounds
0
16. Outline
• Motivation: Current state of toxicology
• High throughput screening
• In vitro in vivo correlation
• CIIPro: An online cheminformatics portal
• CIIProfiler: Chemical in vitro, in vivo profiling
• CIIP Predictor: Using CIIPro to create robust toxicity models
• Demonstration
• The future of CIIPro
16
17. The future of CIIPro 17
Potential
Toxicants
Optimized
Biological Profile
Chemical
Descriptors
In House Animal
Toxicity Data
Toxic
Non-toxic
The future of CIIPro
18. Current State of Toxicology: From databases to researchers
CIIPro: Current State of Toxicology 18
Growing pool
of in vitro
data
Chem. Res. Tox. 2014; (27) 1643-1651
19. Acknowledgements 19
Funding resources:
• National Institute of Health:
1R15ES023148
• Society of Toxicology: Colgate-
Palmolive Grant for Alternative
Research
Acknowledgments Acknowledgments:
Zhu Research Group
Special Thanks to:
Hao Zhu
Marlene Kim
Wenyi Wang
Daniel Pinolini
Kevin Abbey
Zhu Research Group
20. CIIPro: An online cheminformatics portal
CIIPro: An online Cheminformatics portal 20
Questions?
22. Current State of Toxicology: High throughput screening
CIIPro: Current State of Toxicology 22
ToxCast
Growing pool
of in vitro
data
CTD
Tox21
Animal
toxicity data
In vitro - in vivo
correlation
23. Current State of Toxicology: What can we learn from the in vitro data?
CIIPro: Current State of Toxicology 23
Growing pool
of in vitro
data
Animal
toxicity data
Animal
toxicity data
Animal
toxicity data
Animal
toxicity data
Editor's Notes
Large amounts of chemicals without toxicity information
High rate of failure of drugs due to toxicity, adverse drug reactions owing to a lack of understanding of toxicology mechanisms
Ethical concerns on the use of animals, high cost of testing, and difficultly in species extrapolation has pressured alternative methods to prioritize chemical toxicity assessment
-In vitro assays
QSAR, readacross, etc
Large amounts of chemicals without toxicity information
High rate of failure of drugs due to toxicity, adverse drug reactions owing to a lack of understanding of toxicology mechanisms
Ethical concerns on the use of animals, high cost of testing, and difficultly in species extrapolation has pressured alternative methods to prioritize chemical toxicity assessment
-In vitro assays
QSAR, readacross, etc
Large amounts of chemicals without toxicity information
High rate of failure of drugs due to toxicity, adverse drug reactions owing to a lack of understanding of toxicology mechanisms
Ethical concerns on the use of animals, high cost of testing, and difficultly in species extrapolation has pressured alternative methods to prioritize chemical toxicity assessment
-In vitro assays
QSAR, readacross, etc
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
HTS uses robotics in various in vitro cellular assays in a rapid standardized manner
Several fields such as drug discovery and toxicology have undertook large HTS efforts (PDSP, ToxCast) yielding a wealth of compounds linked to rich, biological data
Updated daily, various public repositories (i.e, PubChem) have curated, stored, and made these data publicly available.
Compound response data from PubChem can offer unique insights to a compounds’ in vivo response
