isa-tab-nano a specification to facilitate data exchange among nanotechnology researchers and...

ISA-TAB-Nano

A specification to facilitate data exchange among

nanotechnology researchers and resources

ISA-TAB-Nanohttps://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

Stacey Harper, Oregon State University

Sharon Gaheen, SAIC-Frederick

Target Audiences and Applications

• Audiences• Biomedical researchers• (Nano)-Materials scientists• Toxicologists• Regulatory scientists• Industrial hygienists• …

• Applications• Synthesis• Therapeutics, diagnostics, imaging• Bionics and prosthetics• Risk and exposure assessment• Toxicity prediction and reduction• Laboratory and occupational safety• …

Challenges: Diversity

• Combinatorial complexity in nanoparticle formulation• Diversity of test systems

• Ecosystem vs. organism vs. cell vs. test tube• Species, cell line• Age, gender, weight

• Diversity of measurements and assays• Physical and chemical: size, potential, surface chemistry, shape,

aggregation, …• Biological: toxicity, recognition and association, uptake, delivery, …• Exposure: dose and concentration, timing, duration, …

• Diversity of data resources with lack of common standard for data exchange

Diversity in Composition and Formulation

McNeil SE. J Leukoc Biol, 2005. 78(3): p. 585-94.doi:10.1189/jlb.0205074

Aqueous

Dry

Nanomaterials are Complex 3rd Dimension to the Periodic Table

Photos adapted: Dr. Z Wang, Georgia Tech

Nanomaterials are Complex Diversity of Zinc Oxide Nanoparticles

Assay and Data Diversity

Size Distribution Data

Surface Morphology Data

Tissue Biodistribution

Drug Loading Data

Anti-tumor Activity

In Vitro Drug Release

Zeta Potential

Preparation

Chemical Composition of Nanoparticle Formulation

Source: Chawla JS et al, Int J Pharm, 249, 127-38 (2002), Son YJ et al, J Control Release, 91, 135-145 (2003)

Data Resource Diversity

Goal of ISA-TAB-Nano

Develop a specification to facilitate the exchange ofdata on nanomaterials and their characterizations

to/from nanotechnology resources

What is ISA-TAB-Nano?

• A standard tab-delimited format for describing data related to:• Investigations• Materials (Nanomaterials)• Studies (Specimens)• Assays

• Leverages and extends the Investigation/Study/Assay (ISA-TAB) format• Standard tab-delimited file format• Developed by the European Bioinformatics Institute (EBI) for

representing a variety of assays and technology types• Example: MAGE-TAB

• ISA-TAB-Nano supports ontology-based curation• Nanomaterials and concepts from the NanoParticle Ontology

(NPO) as well as other ontologies

Uses and Benefits

• Address the data sharing challenges in nanomedicine• Provide a standard means for identifying

nanomaterials and characterizations• Enable the submission and exchange of nanomaterial

data to/from nanotechnology data resources ( e.g., NBI, caNanoLab, etc.)

• Empower organizations to adopt standards for representing data in nanotechnology publications

• Provide researchers with guidelines for representing nanomaterials and characterizations to achieve cross-material comparison

ISA-TAB-Nano Structure

1. Describe the Investigation and Studies

2. Identify Study Samples

3. Record Assay Conditions and Measurements

i_xxx.txt m_xxx.txts_xxx.txt a_xxx.txt

Investigation File Study File(s) Material File(s) Assay File(s)

ISA-TAB-Nano Structure

1. Describe the Investigation and Studies

2. Identify Study Samples

3. Record Assay Conditions and Measurements

i_xxx.txt m_xxx.txts_xxx.txt a_xxx.txt

Investigation File Study File(s) Material File(s) Assay File(s)

ISA-TAB-Nano Investigation File

• Describes:• Primary investigation• Associated studies, assays, and protocols

• Descriptive information about the study includes:• Design descriptors and factors• Publications• Assays and protocols• Contacts

• Vertical-based spreadsheet format with columns representing multiple values

Investigation File

Ontology References

Investigation Description

Investigation Contacts

Investigation Publications

Investigation File (cont.)

Study Description

Study Design

Study Contacts

Investigation File (cont.)

Study Publications

Study Assays

Study Factors

Study Protocols

ISA-TAB-Nano Structure: Identify Study Samples

1. Describe the Investigation and Studies

2. Identify Study Samples

3. Record Assay Conditions and Measurements

i_xxx.txt m_xxx.txts_xxx.txt a_xxx.txt

Investigation File Study File(s) Material File(s) Assay File(s)

ISA-TAB-Nano Study File

• Provides mapping between the study samples, materials, and processing events

• Samples can be:• Biological materials• Nanomaterials• Small molecules

• For physical-chemical characterizations of nanomaterials, the sample is the nanomaterial

• For in vitro and in vivo characterizations, the sample is the biological specimen (cell line, animal, etc.)

• Horizontal spreadsheet describing the biological materials and association with the nanomaterials described in the Material file

Study File

Biological Sample Identifier Biological Sample Characteristics Protocol

Biological Sample Study Factors

ISA-TAB-Nano Material File

• Primary file for describing:• Nanomaterial composition and formulation• Physical properties• Structure

• Allows for:• Comparison of nanomaterials across nanotechnology

resources • Association with optional files; e.g., a Structure file for

representing the 3D structure of the nanomaterial• Horizontal spreadsheet describing the nanomaterial

sample, associated components, material characteristics, and material linkages

Material File

Material Identifiers Material Description Intended Application

Material Type Chemical Name Characteristics

Material File (cont.)

Material Linkage Material File

Characteristics

Structure FileNCL Dendrimer-Based MRI Contrast Agents

ATOM 1770 C1 HANDS 1 0.451 -12.517 10.977 0 0 SEGO CATOM 1771 N2 HANDS 1 1.624 -12.647 10.091 0 0 SEGO NATOM 1772 C3 HANDS 1 2.489 -11.674 9.688 0 0 SEGO CATOM 1773 O4 HANDS 1 2.411 -10.485 10.019 0 0 SEGO OATOM 1774 C5 HANDS 1 3.639 -12.175 8.815 0 0 SEGO CATOM 1775 C6 HANDS 1 4.915 -12.278 9.679 0 0 SEGO CATOM 1776 H1 0 HANDS 1 1.879 -13.547 9.725 0 0 SEGO HATOM 1777 1H1 HANDS 1 3.753 -11.471 7.996 0 0 SEGO HATOM 1778 2H1 HANDS 1 3.369 -13.122 8.358 0 0 SEGO HATOM 1779 4H1 HANDS 1 4.724 -12.967 10.502 0 0 SEGO HATOM 1780 5H1 HANDS 1 5.066 -11.299 10.129 0 0 SEGO HTER 1781 HANDS 1ATOM 1782 C1 ARM1S 1 6.188 -12.716 8.918 0 0 SEGP CATOM 1783 N2 ARM1S 1 6.256 -11.808 7.767 0 0 SEGP NATOM 1784 C3 ARM1S 1 7.152 -10.838 7.49 0 0 SEGP CATOM 1785 O4 ARM1S 1 8.254 -10.714 8.012 0 0 SEGP OATOM 1786 C5 ARM1S 1 6.653 -9.788 6.524 0 0 SEGP CATOM 1787 C6 ARM1S 1 7.239 -9.935 5.119 0 0 SEGP CATOM 1788 C7 ARM1S 1 6.112 -9.762 4.124 0 0 SEGP CATOM 1789 O8 ARM1S 1 5.455 -11.03 4.034 0 0 SEGP OATOM 1790 O9 ARM1S 1 3.788 -10.808 5.448 0 0 SEGP OATOM 1791 C1 0 ARM1S 1 4.145 -10.919 4.278 0 0 SEGP CATOM 1792 H1 4 ARM1S 1 5.578 -11.888 7.023 0 0 SEGP HATOM 1793 5H1 ARM1S 1 6.892 -8.808 6.929 0 0 SEGP HATOM 1794 6H1 ARM1S 1 5.569 -9.845 6.51 0 0 SEGP HATOM 1795 7H1 ARM1S 1 7.66 -10.923 4.947 0 0 SEGP HATOM 1796 8H1 ARM1S 1 8.026 -9.201 4.949 0 0 SEGP HATOM 1797 9H1 ARM1S 1 6.474 -9.457 3.155 0 0 SEGP HATOM 1798 0H2 ARM1S 1 5.468 -8.959 4.482 0 0 SEGP HTER 1799 ARM1S 1ATOM 1800 C1 CARBS 1 3.262 -11.048 2.947 0 0 SEGQ CTER 1801 CARBS 1ENDHEADER D ENDR IMER -4 12-2007 DF 40KEYWDS D ENDR IMER FUL LER ENEAUTHOR U SER4COMPND M OL_I D:1;COMPND 2 MOLE CULE: DF 4;COMPND 3 CHAI N: FULLE REN E;COMPND 4 SYNO NYM: ;COMPND 5 EC: ;COMPND 6 ENGI NEERED: YES ;COMPND 7 BIOL OGICAL_UNIT : CARBOXY AMIDO FULL ERENE;

Atom

Header

ISA-TAB-Nano Structure

1. Describe the Investigation and Studies

2. Identify Study Samples

3. Record Assay Conditions and Measurements

i_xxx.txt m_xxx.txts_xxx.txt a_xxx.txt

Investigation File Study File(s) Material File(s) Assay File(s)

ISA-TAB-Nano Assay File

• Describes the protocol parameters and factors, including:• Temperature• Media/solvent• Concentration

• Provides references or links to assay results, including:• Measurements• Instrumentation• Derived data files

• Templates available for the “top Nano WG assays”• Size by DLS (Physico-Chemical)• Zeta Potential (Physico-Chemical)• Hemolysis (In Vitro)• Hepatocarcinoma Cytoxicity (MTT and LDH) (In Vitro)• Caspase 3 Apoptosis (In Vitro)• Toxicity (ADME, Single/Repeat Dose) (In Vivo)• Your assay here!

ISA-TAB-Nano Assay File

• Horizontal-based spreadsheet format with the following sections:• SAMPLE NAMES• PROTOCOL PARAMETERS• ASSAY FACTORS• ASSAY MEASUREMENTS• ASSAY FILES

Assay File Size by DLS

Sample Names Protocol Parameters Assay Factors

Assay Measurements Assay Files

ISA-TAB-Nano Site Walkthrough

Investigation File Example

Study File Examples

Material File Examples

Nanomaterial Examples

Carbon Nanotube: Amine functionalized single wall nanotube with attached

fluorescent oligonucleotide

Dendrimer: G4.5 COONa terminated PAMAM dendrimer-Magnevist® complex

Liposome: Liposome associated with 30% C6-ceramide

Fullerene: C60 fullerene derivatives

Assay File Examples

Assay Examples

Hemolysis

Pharmacokinetics

Tissue Distribution

Pharmacokinetics

Cytotoxicity

Size by Dynamic Light Scattering

Caspase Apoptosis

BioPortal Navigation

ISA-TAB Resources

ISA-TAB-Nano Future

• ISA-TAB-Nano ASTM Ballot• Initial ballot for standard specification

submitted May 2012• Re-balloted as a standard guide.

Estimated ballot completion end of December 2012

• ISA-TAB-Nano Manuscript• Submitted manuscript to BMC

Biotechnology on October 2012• Manuscript was accepted

• ISA-TAB-Nano Users Guide• Basic descriptions of elements, glossary• Organized collection of examples• Tutorials

• Easier NPO Annotation/Integration• List of most relevant terms• List of missing terms

• Real World Applications• “Client” engagement• Friendly user support

https://cananolab.nci.nih.gov/caNanoLab

http://nbi.oregonstate.edu/

Getting Started

1. Contact us for help! nano-tab-l@list.nih.gov

2. Use ISA-TAB-Nano template to create ISA-TAB-Nano files: https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

3. Leverage template glossary for definitions: https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

4. View example files: https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

5. Navigate the BioPortal ontology for terms: http://purl.bioontology.org/ontology/NPO

6. Complete ISA-TAB-Nano files and send to the ISA-TAB-Nano Listserv: nano-tab-l@list.nih.gov

7. http://nbi.oregonstate.edu/

NCI Nano WG ISA-TAB-Nano Site: https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

ISA-TAB-Nano is a Community-Driven Effort

Nanotechnology Toxicology Assays ISA-TAB-Nano

NCI caNanoLab

ONAMINBI

Your Organization

Here!

NIOSHNIL

NIBIBNano-

Registry

NIEHSNTP

NCICSN

Nanomaterials, Characterizations, Protocols

3D Nanomaterial Structures

Nanotechnology Safety Protocols

Nanotechnology Biological

Interactions

Curated Nanomaterial Biological, Environmental Interactions

References

• ISA-TAB-Nano Project Site: https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

• ASTM nano-TAB Work Item WK28974: http://www.astm.org/DATABASE.CART/WORKITEMS/WK28974.htm

• ISA-TAB: http://isatab.sourceforge.net

• caBIG ICR Nano WG Data Standards Document: https://wiki.nci.nih.gov/display/ICR/ISA-TAB-Nano

• NanoParticle Ontology (NPO): http://www.nano-ontology.org

• ISA-TAB-Nano Project Team• Nathan Baker, PNNL

• Dennis Thomas, PNNL• Amy Bednar, ERDC

• Elaine Freund, 3rd Millennium• Marty Fritts, NCL

• Sharon Gaheen, SAIC• Sue Pan, SAIC

• Liz Hahn-Dantona, Lockheed Martin• Stacey Harper, Oregon State University

• Mark Hoover, NIOSH• Fred Klaessig, Pennsylvania Bio Nano

Systems• Juli Klemm, NCI CBIIT

• Mervi Heiskanen, NCI CBIIT• David Paik, Stanford University

• Grace Stafford, The Jackson Laboratory• Todd Stokes, Georgia Tech