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ISA-TAB-Nano OVERVIEW PRESENT=
ATION - a great place to start!
ISA-TAB-Nano Paper: BMC Biote=
chnology 2013, 13:2 Published: 14 January 2013=
p>
Commentary Nature =
Nanotechnology 2013, 8, 73-74 Published: 5 February 2013
ISA Model and Ser=
ialization Specifications
ISA-TAB-Nano: Select each File type template: Investigation | Study | Material | Assay
See each File page for more information and links to examples and glossa=
ries.
Scope
This standard (ISA-TAB-Nano) specifies the format for representing and s=
haring information about nanomaterials, small molecules and biological spec=
imens along with their assay characterization data (including metadata, and=
summary data) using spreadsheet or TAB-delimited files.
Prerequisites
Familiarity with the fields of nanotechnology and nanomedicine is a prer=
equisite for this specification. An understanding of ISA-TAB is recommended=
but not required as the ISA-TAB-Nano specification provides descriptive in=
formation on ISA-TAB as applied to nanotechnology.
Version
The current version of ISA-TAB-Nano is Version 1.3 (March 2020). For dif=
ferences between Version 1.3 and 1.2, refer to the ISA-TAB-Nano 1.3 Release Notes.
ISA-TAB-Nano Introduction
Rationale
The field of nanomedicine faces many challenges in the development of st=
andards to support meaningful data submission and information exchange. Nan=
omaterial characterization requires numerous physico-chemical, in-vitro, an=
d in-vivo assays where measurements mostly depend on non-standardized proto=
cols and diverse technology types. Unfortunately, information describing th=
e nanomaterial, including functionalizing entities and three-dimensional (3=
D) structure, is often represented in an undisciplined fashion. In addition=
, there has been no standard way to associate this information with the dat=
a and metadata from characterization studies. This lack of standardization =
has been a significant deterrent to meaningful data sharing across the nano=
technology community; few publications contain sufficient information to en=
able adequate interpretation of results and successful achievement of exper=
imental reproducibility. Furthermore, there has been very limited success i=
n using non-standardized data to represent or derive structure-activity-rel=
ationships (SARs) that are critical for understanding the effects of nanoma=
terial structure on biological activity in nanomedicine.
Significance
The ISA-TAB-Nano specification is intended to facilitate the submission =
and exchange of nanomaterial descriptions and characterization data (metada=
ta and summary data) along with the other files (raw/derived data files, im=
age files, protocol documents, etc.) among individual researchers and to/fr=
om nanotechnology resources like the NCI=E2=80=99s cancer=
Nanotechnology Laboratory (caNanoLab) portal and the Nanomateria=
l-Biological Interactions (NBI) knowledgebase . ISA-TAB-Nano also serv=
es to empower organizations to adopt standard methods for representing data=
in nanotechnology publications; and to provide researchers with guidelines=
for representing nanomaterials and characterizations to achieve cross-mate=
rial comparison.
ISA-TAB-Nano Development
The ISA-TAB-Nano project is an effort of the National Cancer Institute (=
NCI) Nanotechnology Working Group (Nano WG).
ISA-TAB-Nano Standards Re=
-Use
ISA-TAB
The ISA-TAB-Nano format specification is based on an existing specificat=
ion developed by the ISA-community , namely, the investigation/study/a=
ssay (ISA-TAB) format specification. The ISA-TAB format is use=
d by the =E2=80=98omics=E2=80=99 (proteomics, genomics, metabolomics, and t=
ranscriptomics) communities to share data and metadata associated with diff=
erent assays and technology types in their experiments. The ISA-TAB file st=
ructure relies on three primary files---investigation, study, and assay (IS=
A) files. Raw/derived data files and any other files (such as image files o=
r protocol documents) specific to each assay are shared along with the thre=
e primary ISA-TAB files if the data files are referenced in the primary ISA=
-TAB files. ISA-TAB does not provide format specification for files other t=
han the investigation, study, and assay files. The ISA-TAB investigation fi=
le has three purposes: (1) to record all declarative information referenced=
in other files; (2) to relate assay files to study files; and (3) to group=
multiple study files that are part of the same investigation. The ISA-TAB =
study file records information about the source, sampling methodology, trea=
tment, preparation, and characteristics of the subjects (biospecimens) stud=
ied using one or more assays under an investigation.
National Cancer Institute Enterprise Vocabulary Service (NCI EV=
S)=C2=AD
The NCI EVS is a project of the NCI Center for Biomedical Informatics an=
d Information Technology (CBIIT). EVS provides controlled terminologies and=
ontologies in support of the biomedical research and informatics activitie=
s of the NCI and its partners. The activities of the EVS include developmen=
t of terminologies, development of terminology-related software, and operat=
ions support to address the broad spectrum of terminology needs in the canc=
er research enterprise. Among the vocabularies that EVS supports is the Nan=
oParticle Ontology (NPO), by providing terminology development facilities a=
nd terminology servers, which are made available both via the web and progr=
ammatically through EVS server APIs. Additionally, the NPO is presented to =
the public by EVS both in a standalone format and as a component of the NCI=
Metathesaurus, where its concepts are mapped to the concepts of other voca=
bularies used by the NCI community. Also, the EVS-managed NCI Thesaurus (NC=
It) includes nanotechnology concepts that have been utilized in the develop=
ment of the NCI caNanoLab. Data from caNanoLab has been utilized in the ISA=
-TAB-Nano example files.
NanoParticle Ontology (NPO)=
Like ISA-TAB, ISA-TAB-Nano provides fields for entering and referencing =
terms selected from ontologies and standard terminologies. The ontologies a=
re available at BioPortal , which the National Center for Biomedi=
cal Ontologies maintains. Though the investigator may use alternative ontol=
ogy and vocabulary sources, the ability to evaluate and share data require =
that all parties have access to those being used (they should be available =
to the investigators). All terms and fields used in this standard utilize t=
he NCI EVS and NanoParticle Ontology elements.
NanoParticle Ontology (NPO) is an ontology that is designed=
and developed within the framework of the Basic Formal Ontology (BFO) and =
implemented in the ontology web language (OWL). It is being developed to re=
present the knowledge underlying the description, preparation, and characte=
rization of nanomaterials. NPO development began with the representation of=
knowledge underlying the chemical composition, preparation, physiochemical=
, and functional/biological characterization of nanoparticles that are form=
ulated and tested for applications in cancer diagnostics and therapeutics. =
The NPO provided the knowledge framework for developing the ISA-TAB-Nano ma=
terial file format. The NPO provides a subset of the terms and relationship=
s for the description and characterization of nanomaterials in the ISA-TAB-=
Nano file format. The NPO is being further developed for the following purp=
oses: (1) to provide terms for annotating nanotechnology research data; (2)=
to provide the knowledge framework required for developing data-sharing mo=
dels and standards in nanomedicine; (3) to enable semantic integration of d=
ata; (4) to enable unambiguous interpretation of the description and charac=
terization of nanomaterials; and (5) to enable knowledge-based searching an=
d comparison of nanomaterial descriptions and characterization results.
ISA-TAB-Nano Extensio=
ns to ISA-TAB
While ISA-TAB-Nano leverages the three primary ISA-TAB files, it extends=
ISA-TAB by providing specification for a fourth file (called the material =
file) for representing the composition and characteristics of nanoparticle =
formulations and small molecules. Raw/derived data files and any other file=
s (for example, image files, protocol documents) specific to each assay hav=
e to be shared along with the four primary ISA-TAB-Nano files. ISA-TAB-Nano=
does not provide any specification for how to format files other than the =
four primary files: investigation, study, assay and material files. Althoug=
h ISA-TAB-Nano adopts ISA-TAB field names and their definition in the inves=
tigation, study, and assay files, some of the definitions are modified and =
additional fields are introduced. These modifications and extensions are re=
quired to expand the scope of information captured from nanotechnology data=
sets into the ISA-TAB-Nano files.
=
Distinction between Biological and Non-biological Samples
In nanotechnology, samples from biological and non-biological sources ca=
n be the primary subjects of a study. Therefore, in ISA-TAB-Nano, samples d=
erived from biological sources are called biological specimens or biospecim=
ens (for example, cell line, body fluids, organs, etc.). Whereas, samples d=
erived from non-biological sources are simply called material samples (for =
example, nanomaterials, nanoparticle formulations, small molecules). For ph=
ysico-chemical characterizations of nanomaterials, the sample is the nanoma=
terial. For in-vitro and in-vivo characterizations, the s=
ample is the biological specimen (cell line, animal, and so forth). Hence, =
in ISA-TAB-Nano, the concept of a sample (as used in ISA-TAB specification)=
is redefined to include both biological specimens and material samples. Th=
e ISA-TAB study file can only be used to record the source and characterist=
ics of biospecimens studied in an assay, and cannot support the representat=
ion of materials. Therefore, in ISA-TAB-Nano, the material file describes m=
aterial samples, while the study file describes biospecimens.
Extensions to ISA-TAB Files<=
/h4>
The Table below represents extensions made to each ISA-TAB file in =
support of ISA-TAB-Nano.
ISA-TAB Extension Field Name |
ISA-TAB File |
Purpose |
Investigation Disease |
Investigation |
To capture and retrieve investigations associ=
ated with specific disease modalities such as cancer |
Investigation Disease Term Accession Number=
p> |
Investigation |
To enable semantic interoperability for disea=
se terms |
Investigation Disease Term Source REF |
Investigation |
To enable semantic interoperability for disea=
se terms |
Investigation Outcome |
Investigation |
To enable researchers to review the outcomes =
of investigations for assessing the utility of the investigation in ac=
hieving scientific endpoints |
MATERIAL |
Investigation |
To allow for the identification of materials use=
d in the investigation and associated studies |
Material File Name |
Investigation |
To identify the name of the Material File, which=
lists information about the composition and characteristics of the nanomat=
erials or other small molecules |
Material Source Name |
Investigation |
To identify the name of the nanomaterial or smal=
l molecule associated with the Material File |
Study Disease |
Investigation |
To capture and retrieve studies associated wi=
th specific disease modalities such as cancer |
Study Disease Term Accession Number |
Investigation |
To enable semantic interoperability for disea=
se terms |
Study Disease Term Source REF |
Investigation |
To enable semantic interoperability for disea=
se terms |
Study Outcome |
Investigation |
To enable researchers to review the outcomes =
of studies for assessing the utility of the investigation in achieving=
scientific endpoints |
Study Assay Measurement Name |
Investigation |
To capture the variables measured in an assay=
to support cross study analysis |
Study Assay Measurement Name Term Access=
ion Number |
Investigation |
To enable semantic interoperability for assay=
measurement names |
Study Assay Measurement Name Term Source=
REF |
Investigation |
To enable semantic interoperability for assay=
measurement names |
Measurement Value |
Assay |
To record the endpoint value of an assay meas=
urement within the assay file |
All Fields |
Material |
To describe nanomaterials and small molecules=
|
ISA-TAB-Nano File Structure=
ISA-TAB-Nano uses the three primary files of ISA-TAB-- investigation fil=
e, study file, and assay file; and, introduces a fourth file called the mat=
erial file (Figure 1). Other files such as raw/derived data files, image fi=
les, protocol documents, etc., referenced in the ISA-TAB-Nano files have to=
be shared along with the ISA-TAB-Nano files.
Figure 1. ISA-TAB-Nano File Structure
ISA-TAB specifies that the names of the primary files end with .txt exte=
nsions. ISA-TAB-Nano file names may end in either .txt or .xls extensions. =
The ISA-TAB-Nano files used as examples in this document were prepared in M=
icrosoft Excel spreadsheets, and so their filenames have the .xls extension=
.
Figure 2 describes the ISA-TAB-Nano file development process.
Typically, the investigation file is developed first and describes the ove=
rall investigation, associated studies and assays. The investigation file i=
s a text file with a naming convention of =E2=80=9Ci_xxx.txt=E2=80=9D or =
=E2=80=9Ci_xxx.xls,=E2=80=9D in which xxx can be any name provided by the i=
nvestigator. Once the investigation file has been completed, one or more st=
udy files (following the convention =E2=80=9Cs_xxx.txt=E2=80=9D or =E2=80=
=9Cs_xxx.xls=E2=80=9D) can be created. Similarly, one or more material file=
s can be created. The material file describes the nanomaterial (or small mo=
lecule) and its components including structural information and follows the=
naming convention =E2=80=9Cm_xxx.txt=E2=80=9D or =E2=80=9Cm_xxx.xls=E2=80=
=9D. Assay files (following the convention =E2=80=9Ca_xxx.txt=E2=80=9D or =
=E2=80=9Ca_xxx.xls=E2=80=9D) are created for all assays performed. Each ass=
ay is defined by the endpoint measured and the technique used to measure th=
at endpoint. Data files (raw or derived) specific to each type of assay can=
be associated to the respective assay files by referencing the names of th=
e data files in the assay files.
Figure 2. ISA-TAB-Nano File Development Process
When sharing primary ISA-TAB-Nano files, other files referenced in these=
files have to be shared along with the primary files. It is anticipated th=
at content management systems will become available to facilitate the shari=
ng and exchange of files. Until then, these files could be bundled together=
in a folder and shared as a zip file.
Once the ISA-TAB-Nano files have been created, the files can be validate=
d and submitted into nanotechnology resources that support the ISA-TAB-Nano=
specification. It is anticipated that validation of the files may occur vi=
a a validation service that leverages a modified version of the ISA-TAB validator .
It is also anticipated that nanotechnology resources like caNanoLab (htt=
ps://cananolab.nci.nih.gov/caNanoLab/ ), the Nanomaterial-Biological =
Interactions (NBI) knowledgebase and other resources will provide fac=
ilities for importing/exporting ISA-TAB-Nano files as the ISA-TAB-Nano spec=
ification evolves.
ISA-TAB-Nano File Templates=
The following pages provide templates for each ISA-TAB-Nano file:
Definitions of terms in each file are available in the ISA-TAB-Nano Glossary Files.=
p>
ISA-TAB-Nano Example Files=
h2>
The following are example ISA-TAB-Nano files for a nanotechnology invest=
igation involving physico-chemical and in vitro characterization studies.=
p>
Investigation Title: Nanotechnology Characterization La=
boratory (NCL) Dendrimer-Based MRI Contrast Agent
Investigation Description:=
The objective of this investigation is to characterize a PAMAM de=
ndrimer with an associated gadolinium chelate MRI contrast agent. The nanom=
aterials submitted for testing at the NCL were:
- (NCL20) G4 tris (hydroxyl) terminated PAMAM dendrimer
- (NCL21) G4 pyrrolidinone terminated PAMAM dendrimer
- (NCL22) G4.5 COONa terminated PAMAM dendrimer
- (NCL23) G4.5 COONa terminated PAMAM dendrimer-Magnevist=C2=AE complex=
li>
- (NCL25) G4 tris (hydroxyl) terminated PAMAM dendrimer-Magnevist=C2=AE c=
omplex
- (NCL26) G4 pyrrolidinone terminated PAMAM dendrimer-Magnevist=C2=AE com=
plex
Commercially available Magnevist=C2=AE (NCL24) was used as a control. Th=
e NCL example files encompass three categories: physicochemical characteriz=
ation; immunotoxicology; in vitro toxicology.
Example Files
ISA-TAB-=
Nano Curated Examples
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