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

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Oct 4, 2013 (3 years and 6 months ago)

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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