Integrated Bioinformatics
Data
and Analysis
Tools for
Herpesviridae
Viruses
in
the Virus Pathogen Resource (
ViPR
)
Yun Zhang
1
, Brett Pickett
1
, Eva
Sadat
2
,
, R. Burke
Squires
2
,
Jyothi
Noronha
2
,
Sanjeev
Kumar
3
,
Sam
Zaremba
3
,
Zhiping
Gu
3
,
Liwei
Zhou
3
,
Chris
Larsen
4
,
Wei
Jen
3
,
Edward B.
Klem
3
,
Richard H.
Scheuermann
1
1
J. Craig Venter Institute, San Diego,
CA;
2
Department
of
Pathology,
Univ. of Texas Southwestern Medical Center, Dallas, TX;
3
Northrop
Grumman Health Solutions, Rockville MD;
4
Vecna Technologies, Greenbelt MD.
Introduction
Figure
2
:
A
screenshot
of
the
GBrowse
window
.
The
“
Overview”
panel
displays
the
entire
genome
;
the
“Region”
panel
displays
a
portion
of
the
genome
surrounding
a
specified
region
;
the
“Details”
panel
displays
several
tracks
of
genomic
features
.
1
Pickett
,
B
.
E
.
,
et
al
.
(
2012
)
ViPR
:
an
open
bioinformatics
database
and
analysis
resource
for
virology
research
.
Nucl
.
Acids
Res
.
40
(D
1
)
:
D
593
-
D
598
2
Darling
,
A
.
C
.
E
.
,
et
al
.
(
2004
)
Mauve
:
Multiple
Alignment
of
Conserved
Genomic
Sequence
With
Rearrangements
.
Genome
Res
.
,
14
:
1394
-
1403
3
Edgar,
R
.
C
.
(
2004
)
MUSCLE
:
multiple
sequence
alignment
with
high
accuracy
and
high
throughput
.
Nucleic
Acids
Res
.
32
(
5
)
:
1792
-
1797
.
4
Zmasek
,
C
.
M
.
and
Eddy
,
S
.
R
.
(
2001
)
ATV
:
display
and
manipulation
of
annotated
phylogenetic
trees
.
Bioinformatics
,
17
,
383
-
384
.
5
Hanson
,
R
.
(
2010
)
Jmol
-
a
paradigm
shift
in
crystallographic
visualization
.
Journal
of
Applied
Crystallography
,
43
,
1250
-
1260
.
We
would
like
to
thank
the
primary
data
providers
for
the
data
that
was
used
throughout
this
study
.
We
also
recognize
the
scientific
and
technical
personnel
responsible
for
supporting
and
developing
ViPR
,
which
has
been
wholly
supported
with
federal
funds
from
the
NIH/NIAID
(N
01
AI
2008038
to
R
.
H
.
S
.
)
.
Figure
6
:
3
D
P
rotein
Structure
Viewer
5
in
ViPR
.
A
display
of
a
3
D
protein
structure
for
the
Thymidine
Kinase
protein
from
Herpes
Simplex
Type
1
virus
.
Ligands,
epitopes
and
active
sites
are
highlighted
(PDB
ID
:
1
E
2
I)
.
ViPR
combines
the
strength
of
a
relational
database
with
a
suite
of
integrated
bioinformatics
tools
to
support
everything
from
basic
sequence
and
structural
analyses
to
genotype
-
phenotype
studies
and
host
-
virus
interaction
studies
.
The
uniqueness
of
ViPR
lies
in
:
•
integrating data from various sources
•
capturing unique data
on the
host
response
to virus
infection
•
combining
the
available
tools
to
quickly
perform
complex
analytical
workflows
•
facilitating
rapid
hypothesis
generation
using
bioinformatics
methods
for
subsequent
experimental
testing
•
allowing data sharing and storage with collaborators
Figure
1
:
A
screenshot
of
the
ViPR
homepage
The
ViPR
homepage
is
the
portal
used
to
access
the
various
types
of
data
and
advanced
functionality
for
any
supported
virus
family
.
The
Virus
Pathogen
Database
and
Analysis
Resource
(ViPR,
www
.
viprbrc
.
org
),
sponsored
by
the
National
Institute
of
Allergy
and
Infectious
Diseases
serves
as
a
single
publicly
-
accessible
repository
of
integrated
datasets
and
analysis
tools
for
14
different
virus
families
including
Herpesviridae
to
support
wet
-
bench
virology
researchers
focusing
on
the
development
of
diagnostics,
prophylactics,
vaccines,
and
treatments
for
these
pathogens
1
.
ViPR
Supports
14
Virus
Families
Arenaviridae
Flaviviridae
Poxviridae
Bunyaviridae
Hepeviridae
Reoviridae
Caliciviridae
Herpesviridae
Rhabdoviridae
Coronaviridae
Paramyxoviridae
Togaviridae
Filoviridae
Picornaviridae
ViPR
Integrates
Data
from
Many
Sources
•
GenBank
sequence
records,
gene
annotations,
and
strain
metadata
•
Protein
Databank
(PDB)
3
D
protein
structures
•
Immune
epitopes
from
the
Immune
Epitope
Database
(IEDB)
•
Clinical
data
•
Host
Factor
Data
generated
from
the
NIAID
Systems
Biology
projects
and
the
ViPR
-
funded
Driving
Biological
Projects
•
UniProtKB
protein
annotations
•
Gene
Ontology
(GO)
classifications
•
Additional
data
derived
from
computational
algorithms
ViPR
Provides
Analysis
and
Visualization
Tools
•
Multiple
Sequence
Alignment
•
Phylogenetic
Tree
Construction
•
Sequence
Polymorphism
Analysis
•
Metadata
-
driven
Comparative
Genomics
Statistical
Analysis
•
Genome
Annotator
•
Gbrowse
Genome
Viewer
•
Sequence
Format
Conversion
•
BLAST
Sequence
Similarity
Search
•
3
D
Protein
Structure
Visualization
and
Movie
Generation
•
Sequence
Feature
Variant
Type
(SFVT)
Analysis
ViPR
enables
you
to
store
and
share
data
and
results
through
the
ViPR
Workbench
Figure
4
:
Comparative
Genomic
Analytical
tools
in
ViPR
A
multiple
sequence
alignment
of
Human
H
erpesvirus
1
(HHV
-
1
)
(A)
whole
genome
sequences
2
and
(B)
VP
16
nucleotide
sequences
3
.
(
C
)
A
phylogenetic
tree
visualized
with
the
Archaeopteryx
4
tool
shows
the
relationship
between
HHV
-
1
VP
16
proteins,
red
represents
human
while
pink
indicates
unknown
host
.
(
D)
The
Metadata
-
driven
Comparative
Analysis
Tool
for
Sequences
uses
statistics
to
identify
individual
positions
that
correlate
with
a
specified
metadata
attribute
.
A
C
D
Multiple Sequence Alignment,
Phylogenetic Tree
and Metadata
-
driven
Comparative Analysis Tool
3D Protein Structure Viewer
Summary
Acknowledgements
References
GBrowse
for
G
enome Viewing
•
Provides
both
bird’s
eye
and
detailed
views
of
genomes
and
genome
annotations
.
•
Available
for
Reference
Sequences
of
Pox
-
and
Herpes
viruses
.
Host
-
virus Interaction Data
Figure
5
:
Host
Factor
Data
in
ViPR
.
A
host
factor
experiment
result
summary
showing
differentially
expressed
genes
in
human
cells
infected
with
SARS
.
ViPR
groups
viral
proteins
into
clusters
based
on
predicted
orthology
within
a
virus
taxon
to
facilitate
gene/protein
search,
gene
function
inference,
and
virus
evolution
research
.
Viral Protein
Ortholog
Groups
Figure
3
:
A
screenshot
of
the
Ortholog
Group
s
earch
r
esult
page
.
Each
ortholog
group
name
is
linked
to
all
viral
proteins
in
the
same
ortholog
cluster
for
the
selected
taxon
.
ViPR
is currently funding Driving Biological Projects to produce
whole genome sequences
for Human
H
erpesvirus
1 oral or
neurotropic
isolates. Lists of host genes that are
differentially
-
expressed
during infection of human
neuronal
cells will also be
deposited.
B
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