2020 IEEE World Congress on Services (SERVICES)
ViewBovine: A Microservices-Powered Web Application to Support Interactive
Investigation of Bovine Tuberculosis Infection Pathways
Fan Yang-Turner, Denis Volk, Tim Peto
Nuffield Department of Clinical Medicine
University of Oxford
Oxford, United Kingdom
Abstract—Bovine tuberculosis (bTB) is a chronic infectious
disease caused by Mycobacterium bovis (M. bovis) which affects
cattle and a broad range of other mammalian hosts, including
humans. Animal health authorities face the challenge of
identifying epidemiologically linked cases with scattered or
incomplete information. Here, we report a novel microservices-
powered web application, ViewBovine, to support investigations
into bTB incidents by government veterinary inspectors and
epidemiologists. ViewBovine is powered by microservices that
integrate genetically related isolates of M. bovis and cattle
movement information, with web-based visualisation and
interactive features. This enables users to quickly investigate,
evaluate and gain insights into the relatedness of different bTB
cases. We present an evaluation of this tool using three cases
which demonstrate the strengths of the tool and showcase its
usage in practice. Although ViewBovine is designed for bTB, it
demonstrates the successful design and implementation of an
interactive web-based application for routine monitoring of
pathogen infections and outbreak investigation in a timely
manner.
Keywords-genome analysis; bovine TB; interactive design;
microservice; epidemiological study.
I. INTRODUCTION
Bovine tuberculosis (bTB) is an infectious bacterial
disease caused by Mycobacterium bovis (M. bovis) that
threatens cattle industry and presents risks to other livestock,
wildlife and domestic pets. The bovine epidemic in cattle and
badgers in the UK, with occasional spill-over into other
domestic species also represents a low but ongoing public
health risk. For example, almost 4,400 herds experienced new
cases (incidents) of bTB in Great Britain (GB) in 2018 [1].
Investigating a bTB case or groups of cases is a complex
activity that requires a grasp of epidemiological, laboratory
and environmental assessments.
Animal health authorities often face the challenge of
identifying epidemiologically linked cases over a short period
of time in a specific geographical area, or clusters of cases
with a presumptive common source not necessarily clustered
geographically. In this regard, identifying epidemiologically
linked cases and the infection source are essential for risk
assessment, outbreak investigations and to prevent further
bTB transmission.
II. BACKGROUND
Genome analysis of disease-causing microorganisms, likc
bacteria or virus has the potential to radically improve the
detection of disease transmission [2]. Whole Genome
2642-939X/20/$31.00 ©2020 IEEE
DOI 10.1109/SERVICES48979.2020.00014
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Tony Roberts, Juan Herreros, Richard Ellis
Animal and Plant Health Agency
Addlestone, United Kingdom
Sequencing (WGS) has been applied to the study of bTB in
GB and approximately 10,000 M. bovis isolates from cattle
have already been sequenced and analysed by the Animal and
Plant Health Agency (APHA).
Single Nucleotide Polymorphism (SNP) analysis is a
common initial step to rapidly detect the relationships between
sequences of bacteria species. Genetic relatedness can be
defined by the SNP distance, i.e. the number of base-pair
differences between the genomes of two isolates of the same
bacterial species. In some cases, the SNP analysis is sufficient
to generate epidemiologically important information. In other
cases, phylogenetic trees based on evolutionary inference are
also needed to adjust estimates of divergence [3].
The main route of transmission of bTB among cattle is
through respiratory aerosols, which can result in within-herd
spread of infection. It is also known that a large proportion of
new herd infections result from direct movement of infected
animals from endemic bTB areas [4]. Three policy control
zones have been delineated in England according to bTB
incidence risk: a high risk area (HRA) in the south-west, the
Low bTB Risk Area (LRA) and a buffer zone Edge Area (EA)
in between [5].
Epidemiological data such as herd location and historical
movement records of the infected animals are essential
resources for bTB outbreak investigation. Integration of
genetic and epidemiological data to determine transmission
pathways can be an effective approach in traditional
algorithm-statistical analysis [6]. This methodology has
proved that more accurate estimation of transmission
pathways from epidemiological data could be achieved by
incorporating information about the possible movement of
animals between farms [7][8]. In the public health domain,
visual analytics have been recognized as useful tools for
molecular epidemiological studies [9]. A few applications
have been developed to explore this approach [10][11][12].
However, the visualization applications have no interactive
features, setting different parameters for dataset queries and
customizing the views etc. To the best of our knowledge,
ViewBovine is the first web-based application that integrates
epidemiological and genetic data analysis in an interactive
way to investigate bTB transmission.
III. MICROSERVICES APPROACH
To enable our users to explore genetic analytics results and
epidemiological data in an integral view anywhere and
anytime on the web, we took a microservices approach and
designed a substantial API (Application Programming
Interfaces) layer to support data aggregation. We used web
4
service standard RESTful API [13] for integrating the data
from different sources. Our implementation approach has
three advantages. Firstly, an API server has more
computational resources than a web server, managing large
datasets using multiprocessing CPUs to build aggregated
results from different sources. Secondly, APIs cache the result
of searching query and enable repeated queries to respond
quickly. Thirdly, APIs use background processing to update
the new dataset, allowing the current version of data to be
accessed by the end user without any interruption.
ViewBovine APIs aggregate both structured and
unstructured data. To consistently consume the data, it has
been serialized to a JSON format. The APIs are grouped into
three categories to support our three interactive features: 1)
herds with genetically-related samples; 2) genetically related
samples with cattle movement data; and 3) genetic clustering
of isolates with herd location.
As shown in Figure 1, ViewBovine has a microservices
architecture: (i) Data layer that consists of three data sources,
epidemiological data including cattle data (herd location and
cattle movements); Genetic relatedness from WGS data
analytics via a genetic relatedness server [14]; and
Phylogenetic tree data from a tree building server [15] (ii)
Microservices layer that takes epidemiological data, genetic
analytics data and phylogenetic tree from data layer and
aggregates them for a user interface; (iii) UI layer that displays
data retrieved from a microservices layer and provides
interactive visualisation of bTB related cases.
Figure 1. Microservices Architecture of ViewBovine
IV. CASE STUDIES
A. Case Study A: Establishing the Most Likely Source of
Infection
In the LRA, the majority of animals found to be infected have
been purchased from an area of the country with relatively
high prevalence of bTB and were infected before they were
moved [4]. It can be difficult and time consuming to find the
evidence for this. This case was an animal that had tested
positive for bTB on a farm in Bedfordshire located in the
LRA, but had been resident on three farms previously, none
of which had a history of bTB. The initial hypothesis was that
infection had occurred on the farm where it was disclosed
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from test negative but infected (undisclosed infection) cattle.
Analysis of the WGS using ViewBovine indicated that this
particular M. bovis isolate was genetically highly similar to
isolates derived from a cluster of cattle cases in Oxfordshire
which included a farm where this animal had been previously
resident. Using Cohabitation Records (an additional output of
the application), we identified that at this farm, the
Bedfordshire case animal was resident with two infected
animals which also only tested positive after being moved to
other farms (Figure 2). The M. bovis bacteria isolated from
all three cases were part of the same genetic cluster. The
Oxfordshire farm had no bTB history and therefore was not
registered as an infected farm. ViewBovine was able to
identify this farm as the likely source of infection through
combining cohabitation and WGS similarity records. Using
this visualisation allowed the very rapid identification of the
Oxfordshire holding as the source of infection. Without this
information, case investigation would have taken many more
resources and remained inconclusive, or worse, incorrect.
Figure 2. ViewBovine Cohabitation Records allows visualisation of case
cohabitation. Three cases were resident on the same farm in different
periods.
B. Case Study B: Differentiating Infection Sources
In the Edge Area (EA), incidence of bTB has been
increasing for the past few years in contrast to a slight decrease
observed in the HRA [16]. ViewBovine was used to
investigate the underlying cause for the formation of a new
cluster of twenty cases in the EA of the Midlands and in
particular to determine whether it was an area of potential
emerging endemicity for bTB.
A matrix produced from WGS comparative analysis
identified degrees of relatedness between the isolates derived
from cases in the cluster identifying some cases as unrelated.
Use of ViewBovine allowed rapid identification of the closest
related isolates in the database and geographic locations. This
visual matching of movement history, and locations of related
bTB isolates had provided clear evidence that infection had
originated in another location, outside the area under study
(Figure 3).
The remainder of the cases in the cluster which were
closely related, were concluded as likely to have originated by
contact, direct or indirect, with endemic infection (i.e. local
infection involving cattle and/or wildlife).
ViewBovine was subsequently used for every new local
case, facilitating rapid comparative analysis of the closest
genetic isolates in the database and immediate spatial
visualisation. Critically, this informed the epidemiological
investigation identifying probable infection pathways faster
and with a higher degree of certainty than standard methods
using movement records, and genotype databases (see Case
Study C: Local Infection).

Figure 3. ViewBovine facilitates visualization of case movement history. An
isolate from new bTB breakdown (in red) is displayed against the closest
related –within 2 SNP distance- isolates (in blue). The red line indicates the
movement of the cattle from which the isolate originated, illustrating that the
animal had been moved from the area with clustered genetic related cases.
C. Case Study C: Local Infection
For twenty years, the APHA has classified M. bovis
isolates into genotypes based on spoligotype and VNTR
(Variable Number Tandem Repeat) type which provides less
exact information about genetic relatedness than WGS. This
is currently used in parallel to WGS. A cluster of four bTB
incidents occurred within a relatively small area of
Oxfordshire in 2018. M. bovis isolates from each affected
cattle farm were all identified with different genotypes, which
in the absence of whole genome sequence information
appeared to be unrelated. Apart from one genotype which was
endemic to this area, the remaining three were concluded as
likely caused by movement of infected cattle from the HRA.
ViewBovine demonstrated the close geographical clustering
using the map interface, and that the endemic genotype was
only one SNP different to each of the other three. This
information dispelled the confusion created by the presence of
four different genotypes and instead suggested that the M.
bovis isolates from the four farms were closely related
genetically, and all part of local endemic infection. .
V. CONCLUSIONS AND FUTURE WORK
The ability to control and conduct epidemiological
investigations of bTB incidents is a major task of animal
health authorities. Establishing the likely source and route of
transmission of bTB cases can be quite challenging and time-
consuming. With advances in whole genome sequencing of
pathogens and modern bioinformatics pipelines, visualising
both genetic analytics and epidemiological data could play a
critical role in understanding disease behaviour.
Algorithmic-statistical analysis is the dominant method in
genomics data analysis. As more and more bacterial genomes
are sequenced and analysed using high performance
computing in time spans of a few hours, novel data
visualisation tools promise to support scientific discovery to
public and animal health. We introduce a microservices-
powered web application, ViewBovine, to support
investigating bTB cases in a few minutes. The cases described
herein are examples of how ViewBovine has helped
epidemiologists to rapidly investigate and gain insights into
the likely infection sources. In the future, we will seek
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opportunities to include data from wildlife reservoirs of M.
bovis, and to provide scientific evidence on the transmission
of bTB between wildlife animals and cattle. Finally, we
believe that ViewBovine has set a benchmark for
investigating pathogen transmission using a visualisation and
data aggregation approach powered by microservices. We
suggest that the time is ripe to start building interactive
visualisation tools with genetic analytics data augmented with
epidemiological information in the routine monitoring and
surveillance in public and animal health domain.
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