Released by / Effective Date:

PURPOSE

Curation of biomedical information is accomplished by selecting relevant publications, extracting reported text and data, submitting extracted information into ISA-TAB-Nano and caNanoLab, and keeping track of performed activities.

SCOPE

REFERENCES

RESPONSIBILITIES

DEFINITIONS

REAGENTS, MATERIALS AND EQUIPMENT

HEALTH AND SAFETY CONSIDERATIONS

PROCEDURE PRINCIPLES

Summary

Curation of biomedical information is accomplished by selecting relevant publications, extracting reported text and data, submitting extracted information into ISA-TAB-Nano and caNanoLab, and keeping track of performed activities.

    Differences in in nomenclature and structure and the way information is stored exist between caNanoLab and ISA-TAB-Nano. 

1. In caNanoLab, all information regarding an individual material entity is stored in a single object called SAMPLE. This includes material composition, its functionalities, links between its constituents, its physicochemical, in vitro, in vivo, and ex vivo properties derived from experiments reported in the publication. A term “Composition” annotates an object with SAMPLE, which contains information about material composition, its constituents, functionalities, and links between its constituents. A term “Characterization” annotates an object within SAMPLE, which contains information related to an individual assay performed to acquire data providing information about material properties.
2. In ISA-TAB-Nano, all information from a particular publication or an investigation is spread among Investigation, Study, Assay, and Material forms. The detailed description of each form, but Material form, and their associations are provided in a document entitled “Specification documentation: release candidate 1, ISA-TAB 1.0”. This document can be obtained from http://isatab.sourceforge.net/docs/ISA-TAB_release-candidate-1_v1.0_24nov08.pdf. A Material form corresponds to a “Composition” object in caNanoLab. Descriptive information stored in caNanoLab “Characterization” object components, like Design Description and Analysis and Conclusion are stored in the Study Section of Investigation form. Numerical data are stored in Assay form. A Study form provides link between Investigation and Assay forms.

Data curation is performed in six steps.

1. The NCI collaborator provides a list of publications suggested for curation.
2. Publications are evaluated whether they are curable, i.e. comprise information relevant for curation in caNanoLab.
3. Data extraction from the publication.
4. Submission of extracted data into caNanoLab and into ISA-TAB-Nano forms.
5. Information submitted into caNanoLab must be machine-readable, searchable and comply with the established standards.
6. Sending to authors of a publication, a request for additional data and submission of provided additional data into caNanoLab and ISA-TAB-Nano forms.

Initial Steps

1. Create a caNanoLabData folder on a system or server that gets backup regularly. The caNanoLabData folder contains folders, named after institution or collaboration, e.g. USC_UV which contain additional subfolders. These subfolders, e.g., are named after first author of a publication, publication abbreviation, and publication year, e.g. , JCrecente-CampoJCR2019 contain an individual publication, i.e. PDF file and any supplemental data associated with a publication, extracted data, and supplemental data provided by an author. The caNanoLabData folder contains all auxiliary files, e.g. a list of cell lines, a list of all curated publications, a list of chemical compounds, a list of new terms, and recently added list of Bioportal terms.
2. Create a subfolder in caNanoLab folder to store the publication and extracted data. A subfolder name comprises first author name, journal name, and year of publication. Additional subfolder within this subfolder is created to store ISA-TAB-Nano forms.

Extract Data

1. Establish a number of samples, which have different compositions or properties, and a number of characterizations using the information provided in the text, tables, figures, and figures' captions in curated publication.
2. Establish sample names, following the pattern: abbreviation(s) of institution names, name of the first author (without a middle name), a custom abbreviation of the journal title, year of publication, and sample sequential number, e.g. USC_UV-JCrecente-CampoJCR2019-01.
3. Associate samples with characterizations based on information provided in the text, tables, figures, and figures’ captions. This information is kept in a text file listing all samples and associated characterizations (Figure 1).
4. Extract information on the composition, physicochemical, in vitro, and in vivo characterizations, numerical data for each individual sample into a corresponding text file. Replace Greek fonts with English equivalents e.g. α replace with alpha. In units replace μ with u. Check the extracted text for nonstandard hyphens. Remove references to figures and to publications. Rephrase active sentences to passive. For example “We synthesized the previously reported μMOF, Hf-DBA (DBA = 2,5-di(p-benzoato)aniline), and used it as a control.” replace with “The previously synthesized and reported μMOF, Hf-DBA (DBA = 2,5-di(p-benzoato)aniline), was used as a control”.

5. Establish definitions for new terms used in the publication, which are not in the caNanoLab glossary or Bioportal, but in other sources, like Wikipedia, and references therein, Encyclopedic Dictionary of Genetics, Genomics, and Proteomics. Record this definition or term, in a designated text file or if possible enter into caNanoLab, e.g. in targeting functionalized entity, a new target, i.e. gene.

6. If the information provided by the publication on e.g. name of an instrument or a chemical compound does not agree with the information provided somewhere else, like manufacturer catalog, retain for curation information provided by the publication and record a discrepancy for correspondence with authors, in a file, which contains a request for numerical data which were used to generate figures.

   Crecente-Campo J, Guerra-Varela J, Peleteiro M, Gutierrez-Lovera C, Fernandez-Marino I, Dieguez-Docampo A, Gonzalez-Fernandez A, Sanchez L, Alonso MJ. The size and composition of polymeric nanocapsules dictate their interaction with macrophages and biodistribution in zebrafish. J Control Release. 308:98-108 (2019). 1  biopolymer (inulin) small nanocapsule   physicochemical size zeta potential  Figure 1  in vitro cytotoxicity Figure 2  in vivo stability Figure S1 toxicity Figure 4  survival Table S1 Table S2 Table S3 2 biopolymer (inulin) medium nanocapsule physicochemical size zeta potential  Figure 1 in vitro cytotoxicity Figure 2 in vivo stability Figure S1  toxicity Figure 4  survival Table S1 Table S2 Table S3 3  biopolymer (chitosan) small nanocapsule physicochemical size zeta potential Figure 1 in vitro cytotoxicity Figure 2 in vivo stability Figure S1 toxicity Figure 4 survival Table S1 Table S2 Table S3 4 biopolymer (chitosan) medium nanocapsule physicochemical size zeta potential Figure 1 in vitro cytotoxicity Figure 2 in vivo stability Figure S1 toxicity Figure 4 survival Table S1 Table S2 Table S3 5 biopolymer (inulin) fluorescent small nanocapsule  in vitro targeting cell internalization Figure 3  in vivo biodistribution Figure 5 biodistribution Figure 6 biodistribution Figure S3  biodistribution Figure S4 biodistribution Figure S5 6 biopolymer (inulin) fluorescent small nanocapsule  in vitro targeting cell internalization Figure 3  in vivo biodistribution Figure 5 biodistribution Figure 6 biodistribution Figure S3  biodistribution Figure S4 biodistribution Figure S5 7 biopolymer (chitosan) fluorescent small nanocapsule  in vitro targeting cell internalization Figure 3  in vivo biodistribution Figure 5 biodistribution Figure 6 biodistribution Figure S3  biodistribution Figure S4 biodistribution Figure S5 8 biopolymer (chitosan)  fluorescent medium nanocapsule  in vitro targeting cell internalization Figure 3  in vivo biodistribution Figure 5 biodistribution Figure 6 biodistribution Figure S3  biodistribution Figure S4 biodistribution Figure S5

   Figure 1. A typical text showing associations between samples and characterizations.

Submit caNanoLab Data

 Submit extracted information and reported numerical data into caNanoLab following online caNanoLab User Guide, which is accessible by selecting caNanoLab FAQ or Online Help buttons (Figure 2). If submitting a new term in any field in caNanoLab use lowercase.

1. Login into caNanoLab and after successful login select either SAMPLES tab in the top bar or Submit Samples button (Figure 2).
   
   Figure 2. caNanoLab home after login. Selecting tabs allows search samples, protocols, publications, and submission of samples, protocols, and publications.
2. Submit sample name, contact information, i.e. custom generated abbreviation for institution name(s), role (either manufacturer or investigator), and addresses of corresponding authors, first name, middle initial, last name, phone number, email address, and keywords relevant to the publication, into General Info section. The first author is a primary point of contact (Figure 3).
   
   Figure 3.  A General Info window after submission of relevant data. Selecting Composition, Characterization, or Publication buttons on top left allows submission of sample composition, its characterizations, and the corresponding publication citation.
3. Composition submission.
   1. Select Composition button below General Info (Figure 3).
   2. Select nanoparticle entity type from Nanoparticle Entity Type drop down menu.
   3. Particle description into Description field.
   4. Submit sample composition into Nanomaterial entity section. This includes chemical name of sample component, its type from a drop down menu, its full name in the description field, PubChem ID, , and amount. If any of sample components has a function, e.g. targeting, the information is indicated in Inherent Function field (Figure 4). At the time of writing of this document (caNanoLab 2.3.10) the inherent function does not work properly. It is advised to use Functionalized Entity section to submit Inherent Function information (Figure 6, Figure 7). In addition, there only three standard functions in the drop down menu, namely imaging function, targeting function, and therapeutic function. The very first Composing Element comprises information about a whole sample (Figure 5).
   5. If information about a link between functionalized entity and samples components is reported in the publication, then this information is entered into chemical association section (Figure 6).
       
      Figure 4. A window for submission of information about sample constituent
      
      Figure 5. An example of the first composing element
      
      Figure 6. A typical window of functionalized entity
      
      Figure 7.  A typical window for a targeting functionalized entity
      
      Figure 8. A typical chemical association window
4. Characterization submission.
   • Select Characterization button (Figure 3).
   • Select appropriate Characterization Type, i.e. select, either physicochemical, in vitro, or in vivo from a drop down menu (Figure 9).
   • Select from a drop down menu a Characterization Name. If a corresponding Characterization Name or Assay Type are not available, select either other_pc as physicochemical Characterization Name, other_vt for in vitro Characterization Name, other_vv for  in vivo Characterization Name, or other_ex_vv for ex vivo Characterization Name.
   • Select an assay type or enter a new assay type in the Assay Type field drop down menu, if an appropriate assay type is not available.
   • Select Characterization Source from a drop-down menu.
   • Enter a cell line, if a field for a cell line exists.
   • Enter an assay description into a Design and Methods Description field.
   • Enter technique(s) and instrument(s), used in an assay, either by selecting existing technique and instrument or by adding a new technique and instrument into respective drop down menus.
   • If numerical data are available, click the Findings button, then in case a small amount of data, enter number of columns and rows required to accommodate these data, select Update button, annotate columns, and enter data.  In case of large amount of data create a csv file, select Import cvs button, and select a csv file to import. Regarding columns annotation, first one have to select Column Type, either condition or datum. If e.g. numerical data are provided as mean, uncertainty, and number of replications than first Column Name (mean) can be retrieved from drop menu if the name associated with this column exists in the menu, otherwise one have to select other on the bottom of the menu and enter a new corresponding Name into New Column Name field, select Column Value Type (mean), select Column Value Unit. One have to do the same for column holding uncertainties, and number of replications. In case Column Name exists in the drop down menu, one can use the name in in the menu for this first column (mean), but for second and third column one have to proceed above, by selecting other on the bottom of the menu, entering existing Column Name, Column Value Type, and Column Value Unit.
   • Submit the description of the results from an assay into an Analysis and Conclusion field (Figure 10).
     
     Figure 9. A Physicochemical Characterization window
     
     Figure 10. A Physicochemical Characterization window with submitted data
5. Publication submission.
   • Select Publication tab (Figure 3).
   • Select a Publication Type for a drop-down menu.
   • Select Publication Status from a drop-down menu.
   • Enter PubMed ID and click outside PubMed ID field to obtain a citation for this publication (Figure 8).
   • If the publication does not exist in PubMed, then enter the publication DOI, its title, journal name, year of publication, volume, start and end pages, list of author names, keywords, abstract in Description field.
   • Select Research Categories.
   • Associate the publication citation with submitted samples as follows.
   • Select Search For Samples button.
   • Select Samples associated with the publication from the list of all samples (Figure 11).
   • Click select button on the right side to associate Samples with the publication (Figure 12).
     
     Figure 11. Samples association with the publication
     
     Figure 12. Samples are associated with the publication.
   • Set access to the publication citation as “public”.
6. Review entries submitted into caNanoLab for consistency with information in the curated publication. Correct any issues.
7. Make all samples “public”.

Submit ISA-TAB-Nano Data

At the time of writing of this document, the curation in ISA-TAB-Nano follows the ISA-TAB-Nano 1.3 Release.  More detailed information is provided in ISA-TAB-Nano wiki  https://wiki.nci.nih.gov/display/icr/isa-tab-nano. The ISA-TAB-Nano forms filenames comprise a prefix corresponding to a specific form, i.e. i_ for an investigation form, s_ for a study form, a_ for an assay form, m_ for a material form, a custom abbreviation of institution(s) names, a name of the first author (first name abbreviation, full last name), a custom abbreviation of journal title and a year of publication, e.g. i_USC_UV-JCrecente-CampoJCR2019.  A suffix for Study indicates a study type e.g. physicochemical, in_vitro. A suffix for Assay file in addition to a type of Study is related to, includes a name of assay, e.g. size, zeta potential.

For example:

a_ USC_UV-JCrecente-CampoJCR2019-physicochemical-size-DLS.

Investigation Form

The very first lines of Investigation form (Figure 13) are dedicated to names of ontologies from Bioportal (http://bioportal.bioontology.org). The information about ontologies is added, while creating ISA-TAB-Nano Investigation form and selecting appropriate annotation from Bioportal for terms, which are entered into ISA-TAB-Nano forms. In case, a term exists in multiple ontologies, then the most in depth annotation is selected.

• Enter in Term Source Name field an abbreviation of ontology name.
• Enter URL of ontology in Term Source File field.
• Enter a current version of ontology or ontology release date in Term Source Version field.
• Enter a full ontology name into Term Source Description.

The most applicable ontologies are NanoParticle Ontology (NPO, https://bioportal.bioontology.org/ontologies/NPO), NCI Thesaurus (NCIT, https://bioportal.bioontology.org/ontologies/NCIT),  Eagle-I Research Resource Ontology (ERO, https://bioportal.bioontology.org/ontologies/ERO), Ontology for Biomedical Investigations (OBI, https://bioportal.bioontology.org/ontologies/OBI) Experimental Factor Ontology (EFO, https://bioportal.bioontology.org/ontologies/EFO), Phenotypic Quality Ontology (PATO, https://bioportal.bioontology.org/ontologies/PATO), and BioAssay Ontology (BAO, https://bioportal.bioontology.org/ontologies/BAO). If it is necessary to annotate entries in Material, Study, and Assay files with terms from Ontologies which are not in Ontology Source Reference section than one should enter these Ontologies into this section.

Figure 13. An Ontology Source Reference section in Investigation form

Enter the Investigation information into the Investigation form.

• Investigation Identifier, in most cases, comprising institution names, first author, journal title, and publication year.
• Custom investigation title, e.g. a rephrased publication title.
• Custom investigation description, e.g. an abbreviated abstract.
• Custom investigation outcome.
• PubMed ID.
• Publication DOI.
• Author list.
• Publication title.
• Publication status (published, submitted, in press, in preparation).

Figure 14. A general information section of Investigation form.

Study Section of Investigation Form

Based on information obtained earlier and related to sample characterizations, identify studies and assays, which are common to a specific study.

Figure 15.  A Study Information subsection of a Study Section

 Enter into a Study section of the Investigation form the following.

• Study Identifier, which can comprise Investigation Identifier and study name, e.g. size.
• Custom Study Title.
• Custom Study Description – this may include a short description of all assays, which are included in the study, in case, when several assays are included in a single study.
• Study Disease, if is available, corresponding Term Accession Number from the Bioportal Ontology. (http://bioportal.bioontology.org) and Term Source REF, i.e. a name of a corresponding ontology.
• Custom Study Outcome.
• A Study Filename and its Description are entered after a corresponding Study form is created.
• Study Publication section is left blank, since there is no other publication related to this study besides a publication listed in the Investigation Publications section.

Figure 16. A Study Publication section

Identify Factors, i.e., independent variables manipulated by the investigator with the intention to affect biological systems in a way that they can be measured by an assay. Enter them into Study Factor section (Figure 14). One factor per cell/column e.g. temperature, corresponding Accession Number and Term Source REF from Bioportal, Study Factor Type, its Accession Number, Term Source REF from Bioportal.

Figure 17. A Study Factors section with two factors

Enter into a Study Assay section the following (Figure 18) Study Assay Measurement Type, e.g. hydrodynamic size, corresponding Term Accession Number, Term Source REF, Study Assay Technology Type, e.g. dynamic light scattering, corresponding Term Accession Number, Term Source REF.

• Study Assay Technology Platform, i.e., instrument name, e.g. Zetasizer Nano ZS (Malvern), corresponding Term Accession Number, and Term Source REF.
• Study Assay Measurement Name, outputs from assay measurements e.g. hydrodynamic diameter, corresponding Term Accession Number, Term Source REF.
• Study Assay Filename, which is entered after creating corresponding Assay form.

Figure 18.  A Study Assays section

In case, a protocol is provided (Figure 19), then enter the following.

• Study Protocol Name.
• Study Study Protocol Type and its corresponding Term Accession Number and Term Source REF from Bioportal.
• Study Protocol Description.
• Study Protocol Parameter Name, names of measurable quantities, which remain constant as part of assay, separated by semicolons.
• Study Protocol Components Name, names of instruments, software, reagents etc., which are part of assay, separated by semicolon. Manufacturer names are entered next to the Component Name in parentheses.
• Study Protocol Components Type, an instrument type, e.g. a flow cytometer, separated by semicolon, corresponding Term Accession Numbers from a Bioportal separated by semicolon into Term Accession Number field, Term Source REF, and Term Accession Number. In empty columns to the right of protocols enter Study Protocol Names as preparations for the actual Protocols. This Protocol Names should be enter to Protocol REF field in the Study file (Figure 21B).

Figure 18A. A Study Protocols section

Figure 18B.  A Study Protocols section.

Enter into Study Contacts section information from about a person who is a Contact person.

Figure 19. A Study Contacts section

Material Form

 Create a number of Material forms corresponding to a number of identified samples. In addition to identified samples, which are submitted into caNanoLab, one can create Material forms for substances, like sucrose, saline, or drugs, which are used as control materials.

In the first line of Material form enter the information about a sample.

• Enter to a first column Material Source Identifier, i.e. a sample name as generated in section Data Extraction, e.g. USC_UV-JCrecente-CampoJCR2019-04
• Enter a material name, e.g. core/shell_iron//iron_oxide into Material Name field.
• Enter Manufacturer Lot Identifier, if is available.
• Enter into Material Description a sample description.
• Enter a description of sample synthesis into Material Synthesis field.
• Enter a description of rationale to design specific sample into Material Design Rationale.
• Enter Material Intended Application, its Term Accession Number, and Term Source REF from Bioportal.
• Enter material type, e.g. nanoparticle sample, iron nanoparticle, into Material Type field. If several types are assigned to a sample, separate types by semicolon. Enter corresponding Term Accession Number and Term Source REF separated by semicolon.
• Enter sample properties, e.g. molecular weight, into Characteristics/Material Characteristic field.
• In the next lines, submit information about sample components, as above.
• Enter chemical name of sample component into Material Chemical Name field, corresponding Term Accession Number from Bioportal, and Term Source REF. Check if the Ontology with this Term Accession Number is present in the Ontology Source Reference in the Investigation form (Figure 13). If it is not, then add this Ontology. Perform this process for all other forms and other Term Accession Numbers.
• Enter into Characteristics fields additional information this particular constituent of sample, like amount, functionality, or molecular formula.
• If amount of constituent is specified, enter unit into Unit field and corresponding Term Accession Number from Bioportal and Term Source REF.
• If any two or more components of sample are linked, then in the very first line of Material form, enter Material Names of components, which are linked, into Material Part Name, and add information about a type of association into Material Linkage Type. Enter Term Accession Number corresponding to Material Linkage Type, and its Term Source REF (Figure 20). Repeat this step if the additional components are linked.

Figure 20. Part of Material form showing a linkage subsection

Study and Assay Forms

The number of created Study forms should be equal to the number of Study sections in the Investigation form. In the case of imaging studies, create corresponding Study and Assay forms, when images are available without any restriction. Then, the name of file containing the image is entered into an Image File field of a corresponding Assay form.

Study Form

The number of fields in a Study form and which fields are in this form depends on the number of Study Factors, which are entered in the Investigation form for this particular Study. The common fields in Study form are in all types of Studies are Source Name, Sample Name, Factor and Parameter Values (Figure 18), if both latter are specified in the Investigation form.

• Enter into Source Name, either Material Source Identifier in case of physicochemical Study e.g. USC_UV-JCrecente-CampoJCR2019-04, cell line in case of in vitro characterization e.g. H-1650, or animal name e.g mice in case of in vivo
• Enter material type, either as a free-text description or as a term from Bioportal, its Term Accession Number, and Term Source REF.
• Enter into Characteristics field cell type and cell line in case of in vitro Study or animal type in case of in vivo
• Enter Factor Value, e.g. Material Source Identifier in case, in which an experiment involved only different samples, or entered multiple Factor values. In Sample Name field, enter either name of nanomaterial sample in case, there no Factors, or a name, which includes a combination of sample name, factors numerical values, cell name, and/or animal name. Number of lines in Study form depends on number of Factor Values and numerical Factor Values. 
• Enter protocol name from the corresponding Study Section in the Investigation form into Protocol REF field.
• Enter Study filename into the corresponding Study File Name field in the Investigation form.
  

  

  Figure 21A. Part of a Study form showing primary entries in this form for in vitro assay

  

  Figure 21B. Part of a Study form showing entries in this form for in physicochemical assay

Assay Form

For each study, create a number of Assays forms corresponding to assays in the Study Assay subsection of the Study section in the Investigation form, in case corresponding numerical data are readily available. Enter the following into an Assay form (Figure 19).

• Enter sample names created, while generating corresponding Study form into Sample Name fields.
• Enter protocol name from the corresponding field in the Investigation form into Protocol REF field.
• Enter assay name into Assay Name fields.
• In Measurement Value field replace “measurement term” with appropriate term.
• Enter respective data into Measurement Value fields.  Specify statistic, i.e. mean, standard deviation, and number of replicates in Statistic fields.
• If numerical data possess units, then enter units for mean and standard deviation into Unit field, enter corresponding Term Accession Number and Term Source REF.

Figure 22. Part of Assay form showing important entries

Final Steps

1. Complete the Investigation form by entering Material File Names, Material Source Name, Study File Names, and Assay File Names.

2. Convert all files into csv format. This step can be performed in macOS and Linux platforms using the unoconv script.

   unoconv   -e FilterOptions=9/32,,9 -f csv   -o ../ISA-TAB-Nano_csv  *.xlsx if ISA-TAB-Nano forms were created using the Excel.

Before using this script create the ISA-TAB-Nano_csv folder and run this script from the ISA-TAB-Nano folder in a terminal window.

• In the Investigation form replace all extensions e.g. xlsx with csv using a text editor or a script.
• Compress all forms and associated information into a single compressed file and post the file into the caNanoLab Data Curation Project Wiki under ISA-TAB-Nano Curated Examples including a citation of the publication.
• Update caNanoLab/ISA-TAB-Nano curation status in the caNanoLab Data Curation Project Status file.
• After completing caNanoLab curation provide NCI collaborator with explicit list and description of data needed from investigators to complete curation task.
• Submit to the NCI JIRA tracker reports regarding defects encountered in caNanoLab and requests for improvements.
• Prepare and disseminate weekly report to the Government Sponsor, Project Officer, Leidos Technical Project Manager (COB Friday), and ESI Manager.
• Attend weekly teleconference.
• Prepare and disseminate the monthly report.

ATTACHMENTS

REVISION HISTORY