***Regtransbase* structure (1^st^ level)**

## **Introduction**

*RegTransBase* is a database containing information about regulatory
sequences and interactions as well as descriptions of experiments
concerning those sequences and interactions.

Here we describe the structure of the 1^st^ level of *RegTransBase*
which consists of annotations of literary sources (journal articles). We
also propose the creation of the 2^nd^ level of *RegTransBase* by our
experts, which will contain curated data concerning individual
regulatory interactions.

Annotation of each article in *RegTransBase* contains a set of
*regulatory elements* (i. e. "players" in experiments described in the
article), links between those *elements* and information about each
*experiment* (including a list of elements participating in the
experiment).

Document flow in the 1^st^ level of *RegTransBase*:

\- *Annotator* takes the *package* of articles (as hard copies) in the
office. Also, *curator* sends him a file containing a "blank annotation"
by e-mail. "Blank annotation" contains the title, authors list, abstract
and some other information for each *article* in the *package. Curator*
composes "Blank annotation" file using the *curator program*.

\- Annotator imports the "blank annotation" into the *RegTransBase
annotation program* in his computer. Using the annotation program, he
enters information about experiments and regulatory elements for all of
the articles in the package. When the work is done, the annotator
exports the file with annotation and sends it back to the curator (hard
copies of the articles also should be returned).

\- Curator imports the annotation into the database and checks it using
the curator program. If annotations are true and accurate, he accepts it
(in other cases, he returns package to the annotator for improvement).

# 

# **Objects of RegTransBase 1^st^ level and their properties**

### **1. Package of articles (ExpPackage)**

Package is the number of articles sent to annotator.

# Properties[^1]*: topic_guid, title, topic_path, master_user_id, annotator_id, fl_ready, fl_exported, master_create_date, master_export_date, annotator_export_date, article_date, fl_can_not_change, format_version.*

> *topic_guid:* identifier of articles' topic (topics were added for
> convenience of curator only)

*title:* package name

*topic_path:* path to the package file

*master_user_id*: name of curator who created the package

*annotator_id:* name of annotator who will work with the package

*fl_ready:* "package is ready for export" flag

*fl_exported:* "package was already exported" flag

*master_create_date:* date of package creation

*master_export_date:* date of package export from curator program

*article_date:* currently not used

*fl_can_not_change:* "accepted package" flag (i.e. changes are not
allowed)

*format_version:* for service use

**2. Article (ExpArticle)**

A separate set of regulatory elements and experiments is created for
each article in the package (see below).

When work with article is completed, annotator sets the article in one
of the following states: *Completed*, *Unrelated* or *Unclear*.
"Completed" state means the article contains important information which
was entered into database (i.e. annotation includes at least one
experiment). Annotator sets "Unrelated" state if there were no important
experiments in the article. "Unclear" state used if the annotator can
not make a decision about the article..

Properties: *pkg_guid, title, author, pmid, art_journal, art_year,
art_month, art_volume, art_issue, art_pages, art_abstract, exp_nom,
fl_started, fl_completed, fl_not_by_the_theme, fl_unclear, note*

*pkg_guid:* id of the package, containing the article (here and below)

*title:* article title

*pmid:* article PubMedID

*art_journal, art_year, art_month, art_volume, art_issue, art_pages:\
*article bibliographic data

*art_abstract:* article abstract (as in PubMed)

*exp_nom:* number of experiments in the article

*fl_started:* "Article was sent to annotator" flag

*fl_completed:* "Completed" flag

*fl_not_by_the_theme:* "Unrelated" flag

*fl_unclear:* "Unclear" flag

*note:* Annotator's comment to the article

**3. Regulatory elements**

For each article, annotator input information about regulatory elements
and set up links between them.

***3.1. Types of regulatory elements and their properties***

Regulatory elements are "players" in experiments described in the
article. There are 10 types of regulatory elements (corresponding to 10
objects): [Inductor]{.underline} ([Effector]{.underline}),
[Regulator]{.underline}, [Site]{.underline}, [Gene]{.underline},
[Transcript]{.underline}, [Operon]{.underline}, [Locus]{.underline},
[Regulon]{.underline}, [Helix]{.underline}, и [Secondary
Structure]{.underline}.

*[3.1.1. Inductor/Effector]{.underline}*

Inductor, or Effector, is a substance or physical effect affecting any
regulatory interaction.

Properties: *pkg_guid, art_guid, genome_guid, name, fl_real_name,
descript*

*art_guid:* id of the article, which contain the *regulatory
element*[^2]

*name:* name of the *regulatory element*

*descript:* description of the *regulatory element*

*fl_real_name, genome_guid:* not in use

*[3.1.2. Regulator]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
flag_prot_rna, gene_guid, ref_bank1 -- ref_bank4, consensus, family,
descript*

*fl_real_name:* "Real name" flag. Name used in the article is "real", in
contrast to name invented by annotator.

*genome_guid:* id of genome which contains gene encoded the
regulator[^3]

*flag_prot_rna:* Protein/RNA flag

*gene_guid:* id of the gene encoded the regulator

*ref_bank1 -- ref_bank:* id of the protein in external databases, such
as NCBI

*consensus:* binding site consensus for the regulator

*family:* regulator family

*[3.1.3. Site]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
functional_site_type_guid, structural_site_type_guid, fl_dna_rna,
pos_from, pos_from_guid, pos_to, pfo_type_id, pfo_side_guid,
pos_to_guid, pto_type_id, pto_side_guid, site_len, sequence, signature,
descript*

*functional_site_type_guid:* id of the functional type of the site (from
[FunctionalSiteType]{.underline} dictionary (see below, part 5)).

*structural_site_type_guid:* id of the functional type of the site (from
[StructuralSiteType]{.underline} dictionary (see below, part 5)).

*fl_dna_rna:* DNA/RNA flag

*pos_from, pos_to:* first and last positions of the *regulatory element*

*pos_from_guid, pos_to_guid:* id of the **reference** regulatory
element, which used as point of origin for positions indicated in
*pos_from, pos_to* fields

*pfo_type_id, pto_type_id:* type of the **reference** regulatory
element, which used as point of origin for positions indicated in
*pos_from, pos_to* fields

*pfo_side_guid, pto_side_guid:* id of the relation between **reference**
regulatory element and current regulatory element, which positions are
indicated in *pos_from, pos_to* fields (from [ObjSideType]{.underline}
dictionary (for instance, transcription start, translation start,
transcription end, translation end; see part 5)).

*site_len:* site length

*sequence:* site sequence

*signature:* site signature (if site sequence is too short for certain
localization in the genome, annotator had to input longer sequence
fragment in "signature" field). Signature must be at least 30 nt.

*[3.1.4. Gene]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
location, ref_bank1 -- ref_bank4, signature, metabol_path, ferment_num,
gene_function, descript*

*location:* localization in genome

*signature:* gene signature (30 nt beginning from start codon or 30 aa
from N-end of the protein).

*metabol_path:* metabolic pathway, for genes encoding enzymes or
transporters

*ferment_num:* EC number

*gene_function:* function of the protein encoded by the gene

*[3.1.5. Transcript]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
pos_from, pos_from_guid, pos_to, pfo_type_id, pfo_side_guid,
pos_to_guid, pto_type_id, pto_side_guid, tr_len, sequence, signature,
descript*

*tr_len:* transcript length

*[3.1.6. Operon]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
descript*

*[3.1.7. Locus]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
location, descript*

*[3.1.8. Regulon]{.underline}*

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
reg_guid, descript*

*reg_guid:* id of the regulator for the regulon

*[3.1.9. Secondary structure]{.underline}*

RNA secondary structure

Properties: *pkg_guid, art_guid, name, genome_guid, fl_real_name,
sequence, descript, colors, pos_from, pos_from_guid, pos_to,
pfo_type_id, pfo_side_guid, pos_to_guid, pto_type_id, pto_side_guid*

*sequence:* sequence of the RNA fragment

*colors:* for service use

*[3.1.10. Helix]{.underline}*

RNA helix.

Properties: *pkg_guid, art_guid, name, fl_real_name, genome_guid,
sec_struc_guid, pos_from1, pos_to1, pos_from2, pos_to2, color_id,
descript*

*sec_struc_guid*: id of the RNA secondary structure containing the helix

*pos_from1, pos_to1, pos_from2, pos_to2 :* helix coordinates relative to
start of RNA secondary structure

*color_id:* color marking the helix in curator and annotation programs

***3.2. Regulatory element name synonyms***

All regulatory elements except Inductor (Effector) can have name
synonyms. Name synonyms are stored in [ObjSynonym]{.underline} table.

Properties: *pkg_guid, art_guid, obj_guid, obj_type_id, syn_name,
fl_real_name*

*obj_guid:* id of object, for which the synonym is used

*obj_type_id:* type of object, for which the synonym is used

*syn_name:* name synonym

***3.4. Relations of regulatory elements***

Possibility to establish relations between regulatory elements is an
important feature of *RegTransBase*. "Child" element in relation of two
elements designated as *subelement*. All regulatory element except
Regulator, Effector and Helix can have subelements. Different types of
regulatory elements have different sets of possible subelements (see
table 1).

Any subelement can have several "parents". For instance, regulatory site
controlling expression of two different genes can be a subelement of
those genes.

Table 1. Possible types of subelements

<table style="width:100%;">
<colgroup>
<col style="width: 4%" />
<col style="width: 11%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 10%" />
<col style="width: 12%" />
</colgroup>
<tbody>
<tr class="odd">
<td rowspan="12"><p>S</p>
<p>U</p>
<p>B</p>
<p>E</p>
<p>L</p>
<p>E</p>
<p>M</p>
<p>E</p>
<p>N</p>
<p>T</p></td>
<td colspan="9">E L E M E N T</td>
</tr>
<tr class="even">
<td></td>
<td>Site</td>
<td>Gene</td>
<td>Operon</td>
<td>Transcr.</td>
<td>Locus</td>
<td>Regulon</td>
<td>SecStr</td>
<td>Regulator</td>
</tr>
<tr class="odd">
<td>Site</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="even">
<td>Gene</td>
<td>–</td>
<td>–</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="odd">
<td>Operon</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>+</td>
<td>+</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="even">
<td>Transcr.</td>
<td>–</td>
<td>–</td>
<td>+</td>
<td>–</td>
<td>+</td>
<td>+</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="odd">
<td>Locus</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>+</td>
<td>+</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="even">
<td>Regulon</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="odd">
<td>SecStr.</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="even">
<td>Helix</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>+</td>
<td>–</td>
</tr>
<tr class="odd">
<td>Regulator</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
</tr>
<tr class="even">
<td>Inductor</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>–</td>
<td>+</td>
</tr>
</tbody>
</table>

Links between "parent" and "child" objects are stored in
[SubObjList]{.underline} table.

Properties of

object in SubObjList: *pkg_guid, art_guid, parent_guid, parent_type_id,
child_guid, child_type_id, child_n, strand*

*parent_guid, child_guid:* identificators of "parent" and "child"
objects

*parent_type_id, child_type_id:* types of "parent" and "child" objects

*child_n:* number of current subelement in subelements list of
"parental" object (i. e. object defined by *parent_guid* property)

*strand:* defines which DNA strand (direct or complementary) contains
the element

**4. Experiment**

While working with article, annotator adds experiments to database.
Annotation of each experiment includes list of experimental techniques
used in the experiment, list of regulatory elements studied in the
experiment and description of the experiment (recently, we included
additional field describing the aim of the experiment).

Types of experimental techniques are stored in [ExpTypes]{.underline}
table.

Links to regulatory elements studied in the experiment are stored in
[ExpSubObject]{.underline} table.

***4.1. Experminent object***

Properties: *pkg_guid, art_guid, descript, last_change_date*

*last_change_date:* date of last change of the experiment

***4.2. ExpTypes object***

Properties: *pkg_guid, art_guid, exp_guid, exp_type_guid*

*exp_guid:* id of experiment linked with experimental technique

*exp_type_guid:* id of experimental technique type from
[ExpType]{.underline} table.

***4.3. ExpSubObject object***

Properties: *pkg_guid, art_guid, exp_guid, obj_guid, obj_type_id,
order_num, strand*

*obj_guid:* id of regulatory element

*obj_type_id:* type of regulatory element

*order_num:* number of regulatory element in the list of regulatory
element for current experiment

*strand:* defines which DNA strand (direct or complementary) contains
the element

**5. Dictionaries**

*RegTransBase* contains the following dictionaries:

## Genomes dictionary ([Genome]{.underline})

-   Functional types of site dictionary ([FuncSiteType]{.underline})

-   Structural types of site dictionary ([StructSiteType]{.underline})

-   Types of position dictionary ([ObjSideType]{.underline})

-   Dictionary of experimental techniques ([ExpType]{.underline})

Elements of all dictionaries contains following common properties:
*name, fl_new, user_id*

All dictionaries are created by curator. Complete set of dictionaries
can be exported as a single file for import by annotators in their
annotation programs. Dictionary entry created by curator has property
*fl_new*=FALSE. Annotator also can add entry into any dictionary. Such
entry has property *fl_new*=TRUE and property *user_id* contains
annotator name.

[^1]: All objects also have unique identifier *guid.*

[^2]: If words "*regulatory element*" are used in element property
    description, than regulatory elements described below has the same
    property (even if its description is absent in the text).

[^3]: Links between regulatory elements and genomes are stored also in
    ObjNameGenome table.