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The field of nanomedicine faces many challenges in the development of standards to support meaningful data submission and information exchange. Numerous physico-chemical, in vitro, and in vivo assays must be addressed, with measurements currently dependent on non-standardized protocols and diverse technology types. Representing Structure-Activity-Relationships (SARs) in nanomedicine, in particular, is critical to understanding the effects of nanomaterial structure on biological activity. Unfortunately, information describing the nanomaterial including functionalizing entities and 3D structure is often represented in an undisciplined fashion. 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.
The nano-TAB effort aims to address data sharing challenges in nanotechnology by providing a standard means for identifying nanomaterials and characterizations in a tab-delimited format. 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 describing investigations, studies, and assays and provides extensions to support nanomaterial structural information and concepts from the Washington University NanoParticle Ontology (NPO). 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 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.
The nano-TAB effort is a collaboration between a variety of organizations and 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.
Familiarity with the fields of nanotechnology and nanomedicine is a pre-requisite for this specification. An understanding of ISA-TAB is recommended but not required as the nano-TAB specification provides descriptive information on ISA-TAB as applied to nanotechnology.
1 nano-TAB Introduction
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.
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
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
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.
The NPO is being further developed for the following purposes: 1) to provide terms for annotating data generated from research in nanotechnology, 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).
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 file is developed first and describes the overall investigation and associated studies. The Investigation file is a text file with a naming convention of “i_xxx.txt”, where xxx can be any name provided by the investigator. Once the Investigation file has been completed, one or more Study files (following the convention “s_xxx.txt”) can be created. The Study file describes any samples (biospecimens, nanomaterials, small molecules) leveraged in the study. 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. Assay files (following the convention “a_xxx.txt”) 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 files have been created, the files can be validated and submitted into nanotechnology resources that support the nano-TAB 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. It is also anticipated that nanotechnology resources like caNanoLab, the NBI, and other resources will provide facilities for importing/exporting nano-TAB files as the nano-TAB specification evolves.
1 Relationship to Other Standards
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.
1.2 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.
1.3 LS DAM
The caBIG Life Sciences Domain Analysis Model (LS DAM) 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 nano sub domain, which was developed based on caNanoLab object model and NPO terms. LS DAM makes a distinction between biospecimens (e.g., cell line, tissue samples, body fluid samples, organ parts) and materials that are not derived from a cell, tissue, organ or body (e.g., nanoparticle formulations, drug formulations, solvent, etc.). This motivated the use of the term “material sample” in the nano-TAB material file.