---
id: "edwards-2012-epidemiology-database"
title: "A Public HTLV-1 Molecular Epidemiology Database for Sequence Management and Data Mining"
authors:
  - "Thessika Hialla Almeida Araujo"
  - "Leandro Inacio Souza-Brito"
  - "Pieter Libin"
  - "Koen Deforche"
  - "Dustin Edwards"
  - "Antonio Eduardo de Albuquerque-Junior"
  - "Anne-Mieke Vandamme"
  - "Bernardo Galvao-Castro"
  - "Luiz Carlos Junior Alcantara"
venue: "PLoS ONE"
year: 2012
date: "2012-09-10"
doi: "10.1371/journal.pone.0042123"
url: "/research/publications/10-1371-journal-pone-0042123/"
pdf: "/research/publications/10-1371-journal-pone-0042123/dustin-edwards-10-1371-journal-pone-0042123.pdf"
pmc: "https://pmc.ncbi.nlm.nih.gov/articles/PMC3438164/"
openAccess: true
license: "cc-by"
citedBy: 18
citedBySource: "OpenAlex, read 2026-09-12"
---
# A Public HTLV-1 Molecular Epidemiology Database for Sequence Management and Data Mining

A public online database of 2,457 HTLV-1 sequences.

## Abstract

Background: It is estimated that 15 to 20 million people are infected with the human T-cell lymphotropic virus type 1 (HTLV-1). At present, there are more than 2,000 unique HTLV-1 isolate sequences published. A central database to aggregate sequence information from a range of epidemiological aspects including HTLV-1 infections, pathogenesis, origins, and evolutionary dynamics would be useful to scientists and physicians worldwide. Described here, we have developed a database that collects and annotates sequence data and can be accessed through a user-friendly search interface. The HTLV-1 Molecular Epidemiology Database website is available at http://htlv1db.bahia.fiocruz.br/. Methodology/principal findings: All data was obtained from publications available at GenBank or through contact with the authors. The database was developed using Apache Webserver 2.1.6 and SGBD MySQL. The webpage interfaces were developed in HTML and sever-side scripting written in PHP. The HTLV-1 Molecular Epidemiology Database is hosted on the Gonçalo Moniz/FIOCRUZ Research Center server. There are currently 2,457 registered sequences with 2,024 (82.37%) of those sequences representing unique isolates. Of these sequences, 803 (39.67%) contain information about clinical status (TSP/HAM, 17.19%; ATL, 7.41%; asymptomatic, 12.89%; other diseases, 2.17%; and no information, 60.32%). Further, 7.26% of sequences contain information on patient gender while 5.23% of sequences provide the age of the patient. Conclusions/significance: The HTLV-1 Molecular Epidemiology Database retrieves and stores annotated HTLV-1 proviral sequences from clinical, epidemiological, and geographical studies. The collected sequences and related information are now accessible on a publically available and user-friendly website. This open-access database will support clinical research and vaccine development related to viral genotype.

## Full text

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A Public HTLV-1 Molecular Epidemiology Database for
Sequence Management and Data Mining
Thessika Hialla Almeida Araujo1., Leandro Inacio Souza-Brito2., Pieter Libin3,5, Koen Deforche5,
Dustin Edwards4, Antonio Eduardo de Albuquerque-Junior1, Anne-Mieke Vandamme3,6,
Bernardo Galvao-Castro1,2, Luiz Carlos Junior Alcantara1,2*
1 Gonc¸alo Moniz Research Center/Oswaldo Cruz Foundation, Salvador, Bahia, Brazil, 2 Bahia School of Medicine and Public Health/Bahia Foundation for Science
Development, Salvador, Bahia, Brazil, 3 Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, Belgium, 4 Animal Models and Retroviral Vaccines
Section, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, United States of America, 5 MyBioData, Rotselaar,
Belgium, 6 Centro de Mala´ria e outras Doenc¸as Tropicais, Instituto de Higiene e Medicina Tropical, Universidade Nova de Lisboa, Lisbon, Portugal
AbstractBackground: It is estimated that 15 to 20 million people are infected with the human T-cell lymphotropic virus type 1
(HTLV-1). At present, there are more than 2,000 unique HTLV-1 isolate sequences published. A central database to
aggregate sequence information from a range of epidemiological aspects including HTLV-1 infections, pathogenesis,
origins, and evolutionary dynamics would be useful to scientists and physicians worldwide. Described here, we have
developed a database that collects and annotates sequence data and can be accessed through a user-friendly search
interface. The HTLV-1 Molecular Epidemiology Database website is available at http://htlv1db.bahia.fiocruz.br/.Methodology/Principal Findings: All data was obtained from publications available at GenBank or through contact with
the authors. The database was developed using Apache Webserver 2.1.6 and SGBD MySQL. The webpage interfaces were
developed in HTML and sever-side scripting written in PHP. The HTLV-1 Molecular Epidemiology Database is hosted on the
Gonc¸alo Moniz/FIOCRUZ Research Center server. There are currently 2,457 registered sequences with 2,024 (82.37%) of
those sequences representing unique isolates. Of these sequences, 803 (39.67%) contain information about clinical status
(TSP/HAM, 17.19%; ATL, 7.41%; asymptomatic, 12.89%; other diseases, 2.17%; and no information, 60.32%). Further, 7.26% of
sequences contain information on patient gender while 5.23% of sequences provide the age of the patient.Conclusions/Significance: The HTLV-1 Molecular Epidemiology Database retrieves and stores annotated HTLV-1 proviral
sequences from clinical, epidemiological, and geographical studies. The collected sequences and related information are
now accessible on a publically available and user-friendly website. This open-access database will support clinical research
and vaccine development related to viral genotype.
Citation: Araujo THA, Souza-Brito LI, Libin P, Deforche K, Edwards D, et al. (2012) A Public HTLV-1 Molecular Epidemiology Database for Sequence Management
and Data Mining. PLoS ONE 7(9): e42123. doi:10.1371/journal.pone.0042123
Editor: Robert Belshaw, University of Oxford, United Kingdom
Received March 8, 2012; Accepted July 2, 2012; Published September 10, 2012
Copyright: ß 2012 Araujo et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits
unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: This work was supported by funds from Brazilian Ministry of Health (TC120/2010). The funders had no role in study design, data collection and analysis,
decision to publish, or preparation of the manuscript.
Competing Interests: Authors Pieter Libin, Koen Deforche and Anne-Mieke Vandamme are employed by MyBioData. All other authors declare no further
conflicts of interests. This does not alter the authors’ adherence to all the PLOS ONE policies on sharing data and materials.
* E-mail: lalcan@bahia.fiocruz.br
. These authors contributed equally to this work.
Introduction
Human T-cell lymphotropic virus type 1 (HTLV-1) is the first
described human retrovirus and was isolated from a patient with
cutaneous T-cell lymphoma [1]. It is the causative agent of tropical
spastic paraparesis/HTLV-1-associated myelopathy (TSP/HAM)
[2,3], adult T-cell leukemia/lymphoma (ATLL) [4], and other
inflammatory diseases such as HTLV-1-associated infectious
dermatitis [5,6] and HTLV-1-associated uveitis (HAU) [7].
HTLV-1 is also associated with rheumatic diseases such as
Sjo¨gren’s syndrome and rheumatoid arthritis [8,9]. It is estimated
that approximately 15 to 20 million people worldwide are infected
with HTLV-1 [10]. Though epidemiological data show that
HTLV-1 has a worldwide distribution [10], HTLV-1 infection is
endemic in southwestern Japan [11,12], sub-Saharan Africa [13],
regions of the Caribbean [14], localized areas in Iran and
Melanesia [15], and Brazil [16].
Since the discovery of HTLV-1 in 1980 [1], numerous studies of
the virus have yielded sequence information from more than 2,000
unique isolates. Currently, no single resource is available to
directly compare HTLV-1 sequence information with viral
pathogenesis, transmission, gene polymorphisms, epidemiology,
genotype-phenotype relationships, geographic distribution, and
viral evolution. To further our understanding of the virus, we have
developed a bioinformatic approach to catalogue, organize, and
structure these annotated sequences into a comprehensible format.
Bioinformatic systems use object-oriented or object-relational
database models to store biological data and notes. These
PLOS ONE | www.plosone.org 1 September 2012 | Volume 7 | Issue 9 | e42123

databases are designed to update, query, and retrieve information
stored in the system [17]. By constructing a database to connect
HTLV-1 genetic sequences and epidemiological data and
organizing them into a relational database with a publically
available and user-friendly web interface, we have created a novel
resource for use in clinical research and vaccine development.
Methods
Collection and storage of data for the HTLV-1 Molecular
Epidemiology Database
The HTLV-1 sequences and notes were taken directly from
GenBank and submitted to the BLAST algorithm (Basic Local
Alignment Search Tool) [18] in order to compare the information
obtained from nucleotide sequences with those contained in the
library or from the tool base itself. Data mining from collected
sequences was performed to ensure information integrity, deter-
mine consistent patterns and systematic relationship between
variables, and to remove unrelated sequences. Notes missing from
GenBank were collected from their respective primary publica-
tions or from direct communication with the corresponding
authors. Data were normalized and stored using Apache
Webserver 2.1.6 and SGBD MySQL version 5.5. To facilitate
the addition and manipulation of information, the IDE (Integrated
Development Environment) MySQL-Front version 5.1 trial
(http://www.mysqlfront.de/) was used. The database was initially
modeled using MySQL and information was organized into a
table containing the following fields: ID number, genomic region,
status (complete or partial sequences), isolated, gender, age,
ethnicity, geographic region, continent, clinical profile, proviral
load, date of collection, CD4+, CD8+, sequence length, sequence,
subtype, and subgroup.
Structure of the HTLV-1 Molecular Epidemiology
Database website
The website interfaces were developed in HTML and sever-side
scripting written in PHP. The website interface contains specific
search fields to allow various data combinations. User queries
create a form (form tag) containing the values (variables) selected.
Table 1. Geographical distribution of collected HTLV-1 sequences by clinical profile.
Clinical profile
Geographic region n (%) TSP/HAM ATL Asymptomatic Other Diseases No information
Africa 311 (15.3) 20 12 63 7 209
Asia 612 (30.2) 219 83 108 18 184
Central America 53 (2.6) 10 3 9 12 19
South America 755 (37.3) 62 12 75 6 600
North America 30 (1.5) 4 10 0 0 16
Europe 59 (2.9) 8 7 2 0 42
Oceania 49 (2.4) 0 1 2 1 45
No information 155 (7.8) 25 22 2 0 106
Total 2,024 348 (17.19%) 150 (7.41%) 261 (12.89%) 44 (2.17%) 1221 (60.2%)
doi:10.1371/journal.pone.0042123.t001
Figure 1. The HTLV-1 Molecular Epidemiology Database website interface. Search variables include genomic region, subtype, subgroup,
sampling date, geographic origin, continent, age, gender, ethnicity, proviral load, CD4+ and CD8+ cell counts, and clinical status.
doi:10.1371/journal.pone.0042123.g001
A Public HTLV-1 Molecular Epidemiology Database
PLOS ONE | www.plosone.org 2 September 2012 | Volume 7 | Issue 9 | e42123

This form generates a script that retrieves the data stored in the
MySQL database. A second script organizes the data for display
on the website, allowing for visualization of the information with
the option to download the organized data. The developed
database provides information regarding the indexed sequences in
GenBank. The user is able to choose search criteria and perform a
query to generate an output of relevant sequences and informa-
tion. The sequence output may be downloaded in FASTA format
and the information table in Microsoft Excel spreadsheets .xls
format. The HTLV-1 Molecular Epidemiology database is hosted
on the Gonc¸alo Moniz Research Center/Oswaldo Cruz Founda-
tion Research Center server with access at http://htlv1db.bahia.
fiocruz.br/.
Results
Of the 2,457 sequences stored in the HTLV-1 Molecular
Epidemiology Database, 1,933 (78.67%) sequences represent
unique isolates. In addition, 91 (3.7%) sequences were added that
did not contain isolate information in the GenBank notes.
Sequences with unknown isolate information were analyzed by
genomic region description and by country of origin. Sequences
were identified as individual sequences by BLAST (identity ,90%)
and phylogenetic analysis (support ,70%). Further, we reviewed
sequences collected from GenBank and selected only those
sequences that were relevant to the proposed database. We
excluded clones and sequences from patients who had in the
description the term ‘‘HTLV-1 or HTLV-I’’, but were the result of
another virus, such as HIV.
In total, 2,024 sequences were stored and made publically-
accessible from the database. Of these sequences, 803 (39.67%)
contain information about clinical status (TSP/HAM, 17.19%;
ATL, 7.41%; asymptomatic, 12.89%; other diseases, 2.17%; and
no information, 60.32%). In addition, 1,869 (92.8%) of sequences
contain information about their geographic region of origin
(Table 1). To determine the geographic origin of sequences, data
was derived from either Genbank (73.5% of sequences) or from
original publications and author correspondence (26.5% of
sequences). Of the total sequences analyzed, 1,049 contained
subtype information. This data was collected from Genbank
(15.1% of sequences), articles (69% of sequences), and from LASP
HTLV-1 subtyping Automated Tool (15.9% of sequences). In
addition, 7.26% of sequences contain information on patient
gender while 5.23% of sequences provide the age of the patient.
The database is capable of searching stored HTLV-1 sequences
by one or more specific criteria. The initial website interface
contains variable fields to allow the user to refine the query output
(Fig. 1). Current variables include genomic region, subtype,
subgroup, geographic region of origin, and continent of origin.
Additional variables include patient information such as age,
gender, ethnicity, clinical status, proviral load, and CD4+ and
CD8+ cell counts. Once the search variables are determined, the
algorithm will retrieve the information and post the results as a
table (Fig. 2). The results may then be downloaded in FASTA or
CSV file format (Fig. 3). Currently, the HTLV-1 Molecular
Epidemiology Database contains a Tutorial section and a map of
the HTLV-1 open reading frames (ORFs) from the ATK-1
sequence [19]. These tools were designed to aid new users in
developing advanced queries and interpreting returned results.
Discussion
An important observation in the development of the database
was the lack of complete information on the sequences in
Genbank. There are variables in the HTLV-1 Molecular
Epidemiology Database that are less complete than others, such
as age, gender, and ethnicity. This is because the information is
deficient in the publications and the authors have not made this
information available. To fill the information gaps, we contacted
the original authors and requested the missing data. Because of the
difficulty in acquiring missing data, we encourage authors to
provide more comprehensive information when submitting
annotated sequences for publication in databases. These data
are effective in making public health policies and for planning
programs to combat the spread of infection.
Biological databases are essential tools to assist researchers in
understanding, assessing, and comparing data generated from
their research. Due to the large amount of knowledge created and
the distribution of this information across different databases, it is
difficult to ensure consistency and reliability of this data. The
database described here proposes to aggregate information related
to HTLV-1 sequences, thereby reducing redundancy and
preserving data consistency, either from GenBank or related
publications. We have developed a database of annotated HTLV-
1 proviral sequences from clinical, epidemiological, and geograph-
ical studies that is accessible on a publically available and user-
Figure 2. The HTLV-1 Molecular Epidemiology Database query results table. Retrieved information is posted as a table and the results may
then be downloaded.
doi:10.1371/journal.pone.0042123.g002
Figure 3. The HTLV-1 Molecular Epidemiology Database
download page. Sequence results may be downloaded in FASTA or
CSV file format.
doi:10.1371/journal.pone.0042123.g003
A Public HTLV-1 Molecular Epidemiology Database
PLOS ONE | www.plosone.org 3 September 2012 | Volume 7 | Issue 9 | e42123

friendly website. This open-access database will support clinical
research and vaccine development related to viral genotype. At
present, the database contains more than 1,900 annotated
sequences. We will provide regular updates to the database as
new data becomes available. In the future we plan to incorporate
new analysis tools into the website.
Acknowledgments
The first and second authors contributed equally to this work. We thank
the authors who provided the information by email and through Genbank
(http://www.ncbi.nlm.nih.gov/genbank/).
Author Contributions
Conceived and designed the experiments: LCJA AMV. Performed the
experiments: THAA LISB PL KD. Analyzed the data: THAA DE LCJA.
Contributed reagents/materials/analysis tools: LCJA BGC AEAJ. Wrote
the paper: THAA DE LCJA.
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A Public HTLV-1 Molecular Epidemiology Database
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