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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

The nanotechnologies (nano) tab-delimited (TAB) format is a general purpose framework that provides a standard means to communicate metadata (i.e., study details, material characteristics, assay measurements etc.), data on nanomaterial physicochemical properties, as well as data from in vitro and in vivo experiments of nanomaterials.  The nano-TAB standard specification will enable the submission and exchange of nanomaterials to/from nanotechnology resources like the NCI’s caNanoLab nanotechnology portal and the Oregon State University’s Nanomaterial-Biological Interactions (NBI) knowledgebase; empower organizations to adopt standards for representing data in nanotechnology publications; and 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

 \[2\].  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 \[3\].  To date, the lack of standardization has been one of the most significant barriers to data sharing. 

1.2 Significance

The nano-TAB 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) portal \[4[|#_ftn1]\] and the Nanomaterial-Biological Interactions (NBI) knowledgebase \[5[|#_ftn2]\].  Nano-TAB also serves 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-material comparison.

2. nano-TAB Development  and Use

The nano-TAB project is an effort of the National Cancer Institute (NCI) Cancer Biomedical Informatics Grid (caBIG^®^) Nanotechnology Informatics Working Group (Nano WG).  Its proper use as a standard requires familiarity with other components of the caBIG complement of informatics tools that are all designed to support the meaningful exchange of data across the nanotechnology community.  In Section X, the major components of caBIG are described and adjustments to the existing elements of ISA-TAB are given in Section X.

2.1 nano-TAB format’s relationship to other projects

2.1.1 ISA-TAB 

The nano-TAB format specification is based on an existing specification nano-TAB is based on existing standards developed by the European Bioinformatics Institute (EBI) and , namely, the Investigationinvestigation/Studystudy/Assay assay (ISA-TAB) file format, which represents a variety of format specification.  The ISA-TAB format 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 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.The ISA-TAB file structure relies on three primary files---investigation, study, and assay (ISA) files. Raw/derived data files and any other files (e.g., image files, 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 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.

2.1.2 Life Sciences Domain Analysis Model (LS DAM)

The caBIG® (cancer Bioinformatics Grid) LS DAM \[6\] provides a shared view of the semantics of the life sciences domains that are represented by the different workspaces in the caBIG infrastructure. It has a nanotechnology  subdomain, which was developed based on caNanoLab object model and NPO terms. LS DAM makes a distinction between biospecimens (for example, cell line, tissue samples, body fluid samples, organ parts) and materials that are not derived from a cell, tissue, organ, or body (for example, nanoparticle formulations, drug formulations, solvent, and so forth). This motivated the use of the term “material sample” in the nano-TAB material file.  Weekly Nano WG web-conferencing was used to ensure the alignment of nano-TAB with the LS DAM.   

2.2 Use of ontologies and standard terminologies in nano-TAB

Like ISA-TAB, nano-TAB provides fields for entering and referencing terms selected from ontologies and standard terminologies. The ontologies are available at BioPortal (http://www.bioontology.org^{Image Added}), which is maintained by the National Center for Biomedical Ontologies.  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.

3.2.1.4.2 NanoParticle Ontology (NPO)--- NanoParticle Ontology (NPO) \[7\] is an ontology that is designed and developed within the framework of the Basic Formal Ontology (BFO) \[8\] and implemented in the ontology web language (OWL) \[9\]. 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 nano-TAB material file format. The NPO provides a subset of the terms and relationships for the description and characterization of nanomaterials in the nano-TAB file format.  The NPO is being further developed for the following purposes: (1) to provide terms for annotating 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; (4) to enable unambiguous interpretation of the description and characterization of nanomaterials; and (5) to enable knowledge-based searching  and comparison of nanomaterial descriptions and characterization results.[|#_msoanchor_1]

1.3 NanoParticle Ontology

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