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image representing ISA-TAB-Nano Extension - Study, Investigation, Assay, MaterialImage Added

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titleISA-TAB Specification

ISA-TAB-Nano extends ISA-TAB, an existing specification developed by the ISA-commmunity.  Please refer to the ISA-TAB Specification

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for guidelines on the format of ISA-TAB.

ISA-TAB-Nano OVERVIEW PRESENTATION - a great place to start!

ISA-TAB-Nano Paper:

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BMC Biotechnology 2013, 13:2 Published: 14 January 2013

Commentary

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Nature Nanotechnology 2013, 8, 73-74 Published: 5 February 2013

ISA Model and Serialization Specifications

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ISA-TAB-Nano: Select each File type template: Investigation | Study | Material | Assay

See each File page for more information and links to examples and glossaries.

Scope

This standard (ISA-TAB-Nano) specifies the format for representing and sharing information about nanomaterials, small molecules and biological specimens 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

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prerequisite for this specification.

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An understanding of ISA-TAB is recommended but not required as the

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ISA-TAB-Nano specification provides descriptive information on ISA-TAB as applied to nanotechnology.

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1 nano-TAB Introduction

1.1 Rationale

Nanobioinformatics has been largely recognized as an essential element of our nation’s competitiveness in nanotechnology and a rational approach to employ weight-of-the-evidence strategies that ensure its safe development according to the National Nanotechnology Initiative, 2006. The ability to manipulate matter at the atomic scale will enable a broad range of beneficial applications in the electronics, healthcare (e.g. nanomedicine, imaging, and diagnostics), cosmetics, technologies and engineering industries.  Pertinent to the development of promising biomedical nanotechnologies and to the safety of nanoscale materials in general, is a thorough understanding of nanomaterial-biological interactions.  However, a rational approach must be employed early on in nanotechnology evolution to direct the safe development of novel nanotechnologies and provide accurate predictions of nanomaterial-biological interactions based on weight-of-the-evidence (Dahl et al., 2007; McKenzie and Hutchison, 2004). This inevitably will require data mining and computer simulation for visualization of the important parameters in an almost infinite set of data from global research efforts in nanoscience and nanotechnology (Teeguarden et al., 2007).  To date, the lack of standardization has been one of the most significant barriers to data sharing. 

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Version

The current version of ISA-TAB-Nano is Version 1.3 (March 2020). For differences 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 standards to support meaningful data submission and information exchange. Nanomaterial characterization requires numerous physico-chemical, in-vitro, and in-vivo assays where measurements mostly depend on non-standardized protocols and diverse technology types. Unfortunately, information describing the nanomaterial, including functionalizing entities and three-dimensional (3D) structure, is often represented in an undisciplined fashion. In addition, there has been no standard way to associate this information with the data and metadata from characterization studies. This lack of standardization has been a significant deterrent to meaningful data sharing across the nanotechnology community; few publications contain sufficient information to enable adequate interpretation of results and successful achievement of experimental reproducibility. Furthermore, there has been very limited success in using non-standardized data to represent or derive structure-activity-relationships (SARs) that are critical for understanding the effects of nanomaterial 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 (metadata and summary data) along with the other files (raw/derived data files, image files, protocol documents, etc.) among individual researchers and to/from nanotechnology resources like the NCI’s cancer Nanotechnology Laboratory (caNanoLab nanotechnology ) portal and the Oregon State University’s Nanomaterial-Biological Interactions (NBI) knowledgebase;

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. ISA-TAB-Nano also serves to empower organizations to adopt standards standard methods for representing data in nanotechnology publications; and to provide researchers with guidelines for representing nanomaterials and characterizations to achieve cross-material comparison.  nano-TAB’s extended structure is built on the need to capture the complexity inherent to nanomaterials and their evaluation in many disparate model systems. 

The nano-TAB effort is collaboration between a variety of organizations including the NCI, Washington University, Oregon State University, ONAMI, NIOSH, Stanford University, and ISA-TAB.  nano-TAB is registered as an ASTM Work Item (ASTM WK28974), which facilitates broad community outreach and input to the development of nano-TAB and other standards needed to support nanomedicine.

1.2 nano-TAB Development Process

nano-TAB is based on existing standards developed by the European Bioinformatics Institute (EBI) and the Investigation/Study/Assay (ISA-TAB) file format, which represents a variety of assays and technology types.  The nano-TAB specification leverages ISA-TAB files for describing investigations, studies, and assays and provides extensions to support nanomaterial chemical and structural information and assay measurements.  The development of nano-TAB is being facilitated through the use of knowledge that is represented in the NanoParticle Ontology (NPO).

The development of nano-TAB extensions is a community driven initiative established under the caBIG® Nano Working Group (WG).  Nano WG team members met on a weekly basis during the initial development of nano-TAB extensions and will continue to meet on a scheduled basis once nano-TAB extensions have been formalized with the community.  nano-TAB is a registered ASTM Work Item (ASTM WK28974) and it is expected that community feedback will be received through the caBIG Nano WG, pilot efforts with the NCI Cancer Centers of Nanotechnology Excellence (CCNEs), and the ASTM nanotechnology community.

1.3 NanoParticle Ontology

Wiki Markup
The 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) \[Thomas et al, JBI 2010;  \[http://www.nano-ontology.org\]\]. It is being developed to represent the knowledge underlying the description, preparation and characterization of nanomaterials. NPO development began with the representation of knowledge underlying the chemical composition, preparation, physiochemical and functional / biological characterization of nanoparticles that are formulated and tested for applications in cancer diagnostics and therapeutics. 
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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 specification developed by the ISA-community

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, namely, the investigation/study/assay (ISA-TAB) format specification. The ISA-TAB format
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is used by the ‘omics’ (proteomics, genomics, metabolomics, and transcriptomics) communities to share data and metadata associated with different assays and technology types in their experiments. The ISA-TAB file structure relies on three primary files---investigation, study, and assay (ISA) files. Raw/derived data files and any other files (such as image files or protocol documents) specific to each assay are shared along with the three 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 than the investigation, study, and assay files. The ISA-TAB investigation file 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, treatment, preparation, and characteristics of the subjects (biospecimens) studied using one or more assays under an investigation.

National Cancer Institute Enterprise Vocabulary Service (NCI EVS)­

The NCI EVS is a project of the NCI Center for Biomedical Informatics and Information Technology (CBIIT). EVS provides controlled terminologies and ontologies in support of the biomedical research and informatics activities of the NCI and its partners. The activities of the EVS include development of terminologies, development of terminology-related software, and operations support to address the broad spectrum of terminology needs in the cancer research enterprise. Among the vocabularies that EVS supports is the NanoParticle Ontology (NPO), by providing terminology development facilities and terminology servers, which are made available both via the web and programmatically 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 vocabularies used by the NCI community. Also, the EVS-managed NCI Thesaurus (NCIt) includes nanotechnology concepts that have been utilized in the development 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 are available at BioPortal

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, which the National Center for Biomedical Ontologies maintains. Though the investigator may use alternative ontology 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 the NCI EVS and NanoParticle Ontology elements.

NanoParticle Ontology (NPO)

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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 represent the knowledge underlying the description, preparation, and characterization of nanomaterials. NPO development began with the representation of knowledge underlying the chemical composition, preparation, physiochemical, and functional/biological characterization of nanoparticles that are formulated and tested for applications in cancer diagnostics and therapeutics. The NPO provided the knowledge framework for developing the ISA-TAB-Nano material file format. The NPO provides a subset of the terms and relationships for the description and characterization of nanomaterials in the ISA-TAB-Nano file format. The NPO is being further developed for the following purposes: (1) to provide terms for annotating data generated from research in nanotechnology, nanotechnology research data; (2) to provide the knowledge framework required for developing data-sharing models and standards in nanomedicine, ; (3) to enable semantic integration of data by providing the terms and relationships for data annotation, ; (4) to enable unambiguous interpretation of data pertaining to the description and characterization of nanomaterials, ; and (5) to enable knowledge-based searching of the data for accessing and retrieving relevant information, which in turn facilitates comparison of nanomaterial descriptions and characterization results, leading towards knowledge enhancement and discovery.

The NanoParticle Ontology was primarily developed by Dennis Thomas in collaboration with Nathan Baker and Rohit Pappu.  The NPO development was supported by the NIH through grants U54 CA119342 and U54 HG004028.

2 nano-TAB v0.5 Structure Overview

2.1 nano-TAB Structure

nano-TAB leverages and extends the ISA-TAB file structure to capture nanotechnology metadata (Figure 2-1).

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The ISA-TAB file structure relies on three primary files - Investigation, Study, and Assay files.  Data files specific to each assay can also be provided to capture assay specific measurements.  nano-TAB leverages and extends ISA-TAB by introducing a Materials file for representing the structural composition of the nanomaterial.  nano-TAB extends the ISA-TAB Study file which traditionally provides a mapping between studies and biological specimens, by referencing the Material file for mapping the study to nanomaterials or small molecules.

Each file has a defined structure and is described throughout this section.  Detailed descriptions of the contents of each file with nanotechnology examples are provided in Section 4 and Appendix A.

2.2 nano-TAB file Development Process

Figure 2-2 describes the nano-TAB file development process.  Typically, the Investigation .

ISA-TAB-Nano Extensions 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 files (for example, image files, protocol documents) specific to each assay have 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. Although ISA-TAB-Nano adopts ISA-TAB field names and their definition in the investigation, study, and assay files, some of the definitions are modified and additional fields are introduced. These modifications and extensions are required 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 can be the primary subjects of a study. Therefore, in ISA-TAB-Nano, samples derived from biological sources are called biological specimens or biospecimens (for example, cell line, body fluids, organs, etc.). Whereas, samples derived from non-biological sources are simply called material samples (for example, nanomaterials, nanoparticle formulations, small molecules). For physico-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, 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. The ISA-TAB study file can only be used to record the source and characteristics of biospecimens studied in an assay, and cannot support the representation of materials. Therefore, in ISA-TAB-Nano, the material file describes material samples, while the study file describes biospecimens.

Extensions to ISA-TAB Files

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 associated with specific disease modalities such as cancer

Investigation Disease Term Accession Number

Investigation

To enable semantic interoperability for disease terms

Investigation Disease Term Source REF

Investigation

To enable semantic interoperability for disease terms

Investigation Outcome

Investigation

To enable researchers to review the outcomes of investigations for assessing the utility of the investigation in achieving scientific endpoints

MATERIALInvestigationTo allow for the identification of materials used in the investigation and associated studies
Material File NameInvestigationTo identify the name of the Material File, which lists information about the composition and characteristics of the nanomaterials or other small molecules
Material Source NameInvestigationTo identify the name of the nanomaterial or small molecule associated with the Material File

Study Disease

Investigation

To capture and retrieve studies associated with specific disease modalities such as cancer

Study Disease Term Accession Number

Investigation

To enable semantic interoperability for disease terms

Study Disease Term Source REF

Investigation

To enable semantic interoperability for disease 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 Accession 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 measurement 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 file, study file, and assay file; and, introduces a fourth file called the material file (Figure 1). Other files such as raw/derived data files, image files, 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
diagram of file structureImage Added

ISA-TAB specifies that the names of the primary files end with .txt extensions. 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 Microsoft 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 overall investigation and , associated studies and assays.   The Investigation investigation file is a text file with a naming convention of “i_xxx.txt” , where or “i_xxx.xls,” in which xxx can be any name provided by the investigator.   Once the Investigation investigation file has been completed, one or more Study study files (following the convention “s_xxx.txt” or “s_xxx.xls”) can be created.   The Study file describes any samples (biospecimens, nanomaterials, small molecules) leveraged in the study.  The Material Similarly, one or more material files can be created. The material file describes the nanomaterial (or small molecule) and its components including structural information and follows the naming convention “m_xxx.txt” .  The Material file provides valuable information allowing for cross-particle comparison across nanotechnology resources.  or “m_xxx.xls”. Assay files (following the convention “a_xxx.txt” or “a_xxx.xls”) are created for all assays performed.  Assay files include associated data files that are specific to the assay type being performed.Once the nano-TAB . Each assay is defined by the endpoint measured and the technique used to measure that 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 the data files in the assay files.

Figure 2. ISA-TAB-Nano File Development Process

diagram of ISA-TAB-Nano File Development ProcessImage Added

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 that content management systems will become available to facilitate the sharing 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 validated and submitted into nanotechnology resources that support the nanoISA-TAB-Nano specification.   It is anticipated that validation of the files may occur via a validation service that leverages a modified version of the ISA-TAB validator

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It is also anticipated that nanotechnology resources like caNanoLab (https://cananolab.nci.nih.gov/caNanoLab/ ), the NBI, Nanomaterial-Biological Interactions (NBI) knowledgebase

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and other resources will provide facilities for importing/exporting nanoISA-TAB-Nano files as the nanoISA-TAB-Nano specification evolves.

3 Relationship to Other Standards

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ISA-TAB

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Wiki Markup
nano-TAB file format leverages and extends the investigation, study, and assay files of the ISA-TAB (Investigation/Study/Assay-TAB delimited) format.  The ISA-TAB format is a general purpose framework for sharing metadata and data from omics-based experiments \[ref\].  The ISA-TAB  Investigation file is used for 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 is used to record information about the source, sampling methodology, treatment, preparation, and characteristics of the subjects  (biospecimens) studied using one or more assays under an investigation. The nano-TAB format includes an additional type of file called the Material file which is used to record information about the chemical and structural descriptions of the nanomaterial formulations and other types of chemical samples (e.g., drug formulations). The ISA-TAB Assay file is used to record information about the assay protocols and references to data files.

3.2 NanoParticle Ontology (NPO)

Section 1.3 provides a brief overview of the NanoParticle Ontology (NPO).  The NPO will provide the terms and relationships for the description and characterization of nanomaterials in the nano-TAB file format.  NPO also provides the knowledge framework for developing and using the Material file format.

3.3 LS DAM

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-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.

ISA-TAB-Nano Example Files

The following are example ISA-TAB-Nano files for a nanotechnology investigation involving physico-chemical and in vitro characterization studies.

Investigation Title: Nanotechnology Characterization Laboratory (NCL) Dendrimer-Based MRI Contrast Agent

Investigation Description: The objective of this investigation is to characterize a PAMAM dendrimer with an associated gadolinium chelate MRI contrast agent. The nanomaterials 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® complex
  • (NCL25) G4 tris (hydroxyl) terminated PAMAM dendrimer-Magnevist® complex
  • (NCL26) G4 pyrrolidinone terminated PAMAM dendrimer-Magnevist® complex

Commercially available Magnevist® (NCL24) was used as a control. The NCL example files encompass three categories: physicochemical characterization; immunotoxicology; in vitro toxicology.


Example Files

ISA-TAB-Nano Curated Examples

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