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h2. Description
(1) The nano-TAB investigation file leverages the ISA-TAB investigation file, and it allows for the description of the primary investigation and associated studies including assays and protocols. An investigation can have one or more studies. For example, an investigation titled “Dendrimer-Based MRI Contrast Agents” may have two studies titled as “Characterizing the Size of Dendrimer based MRI Contrast Agents” and “Determining the cytotoxicity property of Dendrimer based MRI Contrast Agents in porcine proximal tubule cells” Each study can have one or more assays depending on the endpoint measured and the technique used. For example, a cytoxicity study may be conducted using an MTT assay and a LDH release assay. While a size characterization study can include two types of assays based on the technique used -- one using DLS and the other using AFM.
(2) The ISA-TAB specification provides flexibility in representing the level of granularity in information associated with a study; however, the level of granularity should factor in the effective representation of assays and protocols in conformance with the specification. For example, a study focusing on “Size Characterizations” will have multiple size measurements (for example, Z-average size, hydrodynamic size) and may involve the use of multiple techniques (for example, size by DLS, size by AFM). These can be represented effectively in the ISA-TAB file structure that nano-TAB uses.
(3) The investigation file provides descriptive information about studies including design descriptors, publications, factors, assays, protocols, and contacts. This descriptive information lays the foundation for other nano-TAB files. For example, TABLE 1 shows a subset of the Investigation File, which is the study factors section of the investigation file. This section provides the names of factors (e.g., temperature, solvent medium) used in the study and their associated units of measurement (if the factors are quantitative). The values of these factors (for example, PBS, 25 Celsius) are specified either in the study or the assay file.
h2. File Format
---The nano-TAB investigation file leverages the ISA-TAB file format, which is a vertical-based spreadsheet format with row headers in the first column, as shown in TABLE 1. The fields are divided into sections as discussed in 5.3. Therefore, the field values in the investigation file are entered in column order. For instance, in TABLE 1, Column A indicates the field names and Columns B and C contain the field values.
TABLE1 Example Subset of the Investigation File Format
| A | B | C |
| STUDY FACTORS | \\ | \\ |
| Study Factor Name | temperature | solvent medium |
| Study Factor Name Term Accession Number | PATO_0000146 | NPO_1855 |
| Study Factor Name Term Source REF | PATO | NPO |
| Study Factor Unit | celsius | \\ |
| Study Factor Unit Term Accession Number | UO_0000027 | \\ |
| Study Factor Unit Term Source REF | UO | \\ |
| Study Factor Type | condition | condition |
| Study Factor Type Term Accession Number | \\ | \\ |
| Study Factor Type Term Source REF | \\ | \\ |
Nano-TAB Extensions--- Nano-TAB extends the ISA-TAB Investigation File specification by introducing new fields, which are listed in TABLE 2.
TABLE2 Extensions and Constraints Applied to the ISA-TAB Investigation File in Support of Nano-TAB
| Section | Field | Change | Field Status (if applicable) |
| INVESTIGATION | Investigation disease | Addition | Required |
| INVESTIGATION | Investigation disease term accession number | Addition | Required |
| INVESTIGATION | Investigation disease term source REF | Addition | Required |
| INVESTIGATION | Investigation outcome | Addition | Optional |
| STUDY | Study disease | Addition | Required |
| STUDY | Study disease term accession number | Addition | Required |
| STUDY | Study disease term source REF | Addition | Required |
| STUDY | Study outcome | Addition | Optional |
| STUDY ASSAYS | Study assay measurement name | Addition | Required |
| STUDY ASSAYS | Study assay measurement name term accession number | Addition | Required |
| STUDY ASSAYS | Study assay measurement name term source REF | Addition | Required |
| STUDY ASSAYS | Study assay measurement unit | Addition | Required |
| STUDY ASSAYS | Study assay measurement unit term accession number | Addition | Required |
| STUDY ASSAYS | Study assay measurement unit term source REF | Addition | Required |
| STUDY ASSAYS | Study assay measurement statistic | Addition | Required |
| STUDY ASSAYS | Study assay measurement statistic term accession number | Addition | Required |
| STUDY ASSAYS | Study assay measurement statistic term source REF | Addition | Required |
| STUDY FACTORS | Study factor unit | Addition | Required |
| STUDY FACTORS | Study factor unit term accession number | Addition | Required |
| STUDY FACTORS | Study factor unit term source REF. | Addition | Required |
| STUDY PROTOCOLS | Study protocol parameter unit | Addition | Required |
| STUDY PROTOCOLS | Study protocol parameter unit term accession number | Addition | Required |
| STUDY PROTOCOLS | Study protocol parameter unit term source REF | Addition | Required |<!-- /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0in 5.4pt 0in 5.4pt; mso-para-margin:0in; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:"Times New Roman"; mso-bidi-theme-font:minor-bidi;} -->TABLE1 Example Subset of the Investigation File Format
| A | B | C |
| STUDY FACTORS | | |
| Study Factor Name | temperature | solvent medium |
| Study Factor Name Term Accession Number | PATO_0000146 | NPO_1855 |
| Study Factor Name Term Source REF | PATO | NPO |
| Study Factor Unit | celsius | |
| Study Factor Unit Term Accession Number | UO_0000027 | |
| Study Factor Unit Term Source REF | UO | |
| Study Factor Type | condition | condition |
| Study Factor Type Term Accession Number | | |
| Study Factor Type Term Source REF | | | |
1.1.1.1 Description
The ISA-TAB Investigation file allows for the description of the primary investigation and associated studies including assays and protocols. For example, an investigation title may be “Dendrimer-Based MRI Contrast Agents” and associated studies may be “Characterizing the Size of Dendrimer based MRI Contrast Agents” and “Determining the Hemolytic Properties of Dendrimer based MRI Contrast Agents”.
The ISA-TAB specification provides flexibility in representing the level of granularity associated with a study; however, the level of granularity should factor in the effective representation of assays and protocols in conformance with the specification. For example, a study focusing on “Size Characterizations” will have multiple size assay measurements (e.g. Z-Average Size, Hydrodynamic Size) and may involve the use of multiple protocols (e.g. Size by DLS, Size by AFFM). These can be represented effectively in the ISA-TAB file structure. A study focusing on “Physico-Chemical Characterizations” would have numerous and diverse assay measurements (e.g. Size, Molecular Weight, Surface, etc.) and protocols and it may be challenging to represent and group the assay measurements and protocols associated with each characterization type.
Studies within the Investigation file provide descriptive information about the study including design descriptors, publications, factors, assays, protocols, and contacts. This descriptive information lays the foundation for other ISA-TAB files. For example, the Study Factors section of the Investigation file provides details of the factors (e.g. media solvent, temperature) used in the study. The value of these factors (e.g. PBS, 25 Celsius) is then specified in the Assay file.
1.1.1.2 File Format
The Investigation file format leverages a vertical based spreadsheet format with columns representing multiple values. In the example subset of the Investigation file below, column A indicates the field names and columns B and C are field values.
...
A
...
B
...
C
...
Study Factor Name
...
temperature
...
media solvent
...
Study Factor Type
...
condition
...
Condition
...
Study Factor Type Term Accession Number
...
Study Factor Type Term Source REF
1.1.1.3 nano-TAB Extensions
In support of nano-TAB, the following extensions and constraints were applied to the ISA-TAB Investigation file and are further described in Section 4.
Field | Change | Description | Field Status |
Term Source Name | Use NPO | Reference the Nanoparticle Ontology (NPO) as the primary ontology supporting nanotechnology studies | Optional |
Investigation Outcome | Addition | Provides a textual description of the outcome(results) of the investigation | Optional |
Study Outcome | Addition | Provides a textual description of the outcome (results) of the study | Optional |
Study file Version | Addition | Indicates the version (e.g. 1.0) of a file | Optional |
Study file Description | Addition | Provides a textual description of the file | Optional |
1.1 Investigation file
The Investigation file is a vertically oriented spreadsheet containing tab delimited column values. The Investigation file consists of the following sections as defined by ISA-TAB:
s ONTOLOGY SOURCE REFERENCE
s INVESTIGATION
s INVESTIGATION PUBLICATION
s INVESTIGATION CONTACTS
s STUDY
º STUDY DESIGN DESCRIPTORS
º STUDY PUBLICATIONS
º STUDY FACTORS
º STUDY ASSAYS
º STUDY PROTOCOLS
º STUDY CONTACTS
An investigation can contain multiple studies. As such the entire study section is typically repeated.
1.1.1 ONTOLOGY SOURCE REFERENCE
An example of the ONTOLOGY SOURCE REFERENCE section of the spreadsheet is provided in Exhibit 4.1 along with example data.
...
A
...
B
...
C
...
ONTOLOGY SOURCE REFERENCE
...
Term Source Name
...
NPO
...
UO
...
Term Source file
...
Term Source Version
...
Term Source Description
...
Nanoparticle Ontology
...
Unit Ontology
Exhibit 4.1 Example ONTOLOGY SOURCE REFERENCE section
Definitions for concepts in the ONTOLOGY SOURCE REFERENCE section are provided below.
Term Source Name - List of ontologies containing terms referenced in the nano-TAB files.
Term Source file - The URI of the ontology.
Term Source Version - Version for each ontology referenced in the nano-TAB files.
Term Source Description - Description of each ontology referenced in the nano-TAB files.
1.1.2 INVESTIGATION
An example of the INVESTIGATION section of the spreadsheet is provided in Exhibit 4.2 along with example data.
...
A
...
B
...
C
...
INVESTIGATION
...
Investigation Identifier
...
NCL200612A
...
Investigation Title
...
Dendrimer-Based MRI Contrast Agents
...
Investigation Description
...
The objective of the Dendritic Nanotechnologies, Inc. - NCL collaboration is to characterize a PAMAM dendrimer with an associated gadolinium chelate MRI contrast agent.
...
Investigation Disease
...
Investigation Disease Term Accession Number
...
Investigation Disease Term Source REF
...
Investigation Outcome
...
Investigation Submission Date
...
2006-12-01
...
Investigation Public Release Date
...
2006-12-01
Exhibit 4.2 Example INVESTIGATION Section
Definitions for concepts in the INVESTIGATION section are provided below.
Investigation Identifier - Name used as an identifier for the investigation.
Investigation Title - Name used as a title for the investigation.
Investigation Description – Text description of the investigation.
Investigation Disease - Disease(s) that are the subject of the investigation, if applicable. Note: This term is a nano-TAB extension.
Investigation Disease Term Accession Number – Identification number of a term selected from an ontology or a controlled vocabulary, and entered as a value for the Disease. Note: This term is a nano-TAB extension.
Investigation Disease Term Source REF - Name of the ontology or controlled vocabulary from which a term is selected and entered as a value for the Disease. Note: This term is a nano-TAB extension.
Investigation Outcome - Text description of the outcome of the investigation. Note: This term is a nano-TAB extension.
Investigation Submission Date - Date the investigation was initiated in the format YYYY-MM-DD.
Investigation Public Release Date - Date the investigation was published or made publically available in the format YYYY-MM-DD.
1.1.3 INVESTIGATION PUBLICATIONS
An example of the INVESTIGATION PUBLICATION section of the spreadsheet is provided in Exhibit 4.3 along with example data.
...
A
...
B
...
C
...
INVESTIGATION PUBLICATIONS
...
Investigation PubMed ID
...
18095846
...
Investigation Publication DOI
...
10.2217/17435889.2.6.789
...
Investigation Publication Author List
...
Hall JB; Dobrovolskaia MA; Patri AK; McNeil SE
...
Investigation Publication Title
...
Characterization of nanoparticles for therapeutics
...
Investigation Publication Status
...
peer reviewed
...
Investigation Publication Status Term Accession Number
...
Investigation Publication Status Term Source REF
...
NPO
Exhibit 4.3 Example INVESTIGATION PUBLICATIONS Section
Definitions for concepts in the INVESTIGATION PUBLICATIONS section are provided below.
Investigation PubMed ID - Identifier of the publication in the PubMed publication source.
Investigation Publication DOI - Publication Document Object Identifier.
Investigation Publication Author List - List of authors separated by semi-colons.
Investigation Publication Title - Name used as a title for the publication.
Investigation Publication Status - The status of the publication.
Investigation Publication Status Term Accession Number - Identification number of a term selected from an ontology or a controlled vocabulary, and entered as a value for the Publication Status.
Investigation Publication Status Term Source REF - Name of the ontology or controlled vocabulary from which a term is selected and entered as a value for the Publication Status.
1.1.4 INVESTIGATION CONTACTS
An example of the INVESTIGATION CONTACTS section of the spreadsheet is provided in Exhibit 4.4 along with example data.
...
A
...
B
...
C
...
INVESTIGATION CONTACTS
...
Investigation Person Last Name
...
McNeil
...
Investigation Person First Name
...
Scott
...
Investigation Person Mid Initials
...
Investigation Person Email
...
...
Investigation Person Phone
...
3018466939
...
Investigation Person Fax
...
Investigation Person Address
...
MSC 1050 Boyles Street, Frederick, MD 21702
...
Investigation Person Affiliation
...
Nanotechnology Characterization Laboratory
...
Investigation Person Roles
...
investigator
...
Investigation Person Roles Term Accession Number
...
Investigation Person Roles Term Source REF
...
MO
Exhibit 4.4 Example INVESTIGATION CONTACTS Section
Definitions for concepts in the INVESTIGATION CONTACTS section are provided below.
Investigation Person Last Name - Last name of the point of contact.
Investigation Person First Name - First name of the point of contact.
Investigation Person Mid Initials – Middle Initials of the point of contact.
Investigation Person Email - Email address of the point of contact
Investigation Person Phone - Phone number of the point of contact.
Inv Investigation Person Fax - Fax number of the point of contact.
Investigation Person Address - Mailing address of the point of contact.
Investigation Person Affiliation - Organization in which the point of contact belongs.
Investigation Person Roles - Role of the point of contact in the investigation.
Investigation Person Roles Term Accession Number - Identification number of a term selected from an ontology or a controlled vocabulary, and entered as a value for Person Roles.
...
