Integrated Bioinformatics Data and Analysis Tools for ... - ViPR

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