Virus Bioinformatics Resource Centers - ViPR/IRD

hordeprobableΒιοτεχνολογία

4 Οκτ 2013 (πριν από 3 χρόνια και 8 μήνες)

67 εμφανίσεις

Richard H. Scheuermann, Ph.D.

Department of Pathology, UT Southwestern

March 30, 2011

Virus Bioinformatics Resource Centers


ViPR

& IRD

Take home messages


NIAID Bioinformatics Resource Centers


Virus Pathogen Resource (
ViPR
;
www.viprbrc.org

)


Influenza Research Database (IRD;
www.fludb.org

)


Free and open access virus database and analysis resources


Comprehensive data collection


Sequence, structure, function, phenotype, surveillance, clinical, immune
response


Integrated


Surveillance metadata with sequence


Sequence features and sequence conservation with protein structures


Development and adoption of data standards


Data sharing infrastructure and policies


Novel approach to identification of genetic determinants of important virus
characteristics


Influenza NS1 nuclear export signal and host range

NIAID RESEARCH
RESOURCES

DMID Resources

DMID Resources List

BRCs

Category A Pathogens

Category B Pathogens

Category C Pathogens

pathogenportal.net

Pathogen Portal

VIPR

RESOURCE

Home page


www.viprbrc.org

13 virus families


Taxonomy browser


Taxonomy browser expanded


Genome statistics


Search, analyze and save


Search


Analysis


Workbench


DATA INTEGRATION

IRD

www.fludb.org


DATA STANDARDS

CEIRS Network



Other

Data Standards


Non
-
human mammalian surveillance


Virus isolate characteristics


Immuno
-
assays


Virus passage


Virus nomenclature


Clinical data

SURVEILLANCE










DATA SHARING

Policies


Sequences



30 days


Initial Surveillance Record


90 days


Completed Virus Isolated Record


1 year

Submission

I
nfrastructure




DO VARIATIONS IN NS1 SEQUENCE
FEATURES

INFLUENCE INFLUENZA VIRUS
HOST RANGE?

SFVT approach

VT
-
1

I F D R L E T L I L

VT
-
2

I F
N

R L E T L I L

VT
-
3

I F D R L E T
I

V

L

VT
-
4

L

F D
Q

L E T L
V

S

VT
-
5

I F D R L E
N

L
T

L

VT
-
6

I F
N

R L E
A

L I L

VT
-
7

I
Y

D R L E T L I L

VT
-
8

I F D R L E T L
V

L

VT
-
9

I F D R L E
N

I

V

L

VT
-
10

I F
E

R L E T L I L

VT
-
11

L

F D
Q

M

E T L
V

S

Influenza A_NS1_nuclear
-
export
-
signal_137(10)


Identify regions of protein/gene with known structural or functional properties


Sequence Features (SF)


alpha
-
helical region,

host protein binding site, enzyme
active site,

immune
epitope


Determine the extent of sequence variation for each SF by defining each unique sequence as a Variant
Type (VT)


High
-
level, comprehensive grouping of all virus strains by VT membership for each SF independently


Genotype
-
phenotype association statistical analysis (virulence, pathogenesis, host range, immune
evasion, drug resistance
)


While
phylogenetics

reflect evolutionary history of the virus, it is the focused regions in the viral
genes/proteins that effect protein expression, structure and/or protein function that are responsible for
important virus characteristics



Influenza A_NS1_alpha
-
helix_171(17)

Protein

Subtype

Functional

Structural

Immune Epitopes

Total Count

PB2

-

7

10

564

585

PB1
-
F2

-

2

2

-

6

PB1

-

6

5

733

744

PA

-

1

29

534

565

NS2

-

2

3

78

83

NS1

-

21

15

458

494

NP

-

10

25

472

512

NA

N1

10

26

113

153

NA

N2

9

59

106

180

M2

-

4

10

96

116

M1

-

12

14

286

312

HA

H1

4

37

335

376

HA

H2

4

10

20

34

HA

H3

2

59

390

481

HA

H5

3

14

40

65

HA

H7

-

1

2

3

Total

97

319

4227

4709

Influenza A Sequence Features as of
January 2011

ViPR

SFVTs


Starting with 3 species


DENV = 192 SF’s


HCV = 335 SF’s


Pox = 14 genes, 295 total SF’s


HSV coming soon
w
/ DBP


Beginning automatic definition for other virus
families


Most SF’s pulled from


UniProtKB

protein annotations


IEDB immune epitopes (future)



NS1 Sequence Features

VT for SF8 (nuclear export
signal)

VT
-
1 strains

VT for SF8 (nuclear export
signal)


Causes of apparent NS1 VT
-
associated
host range restriction


Virus spread = capability + opportunity


Phenotypic property of the virus


limited capacity


Founder
effect


limited opportunity


Restricted spatial
-
temporal distribution


Sampling bias


assumption of random sampling


Oversampling


avian H5N1 in Asia; 2009 H1N1


Undersampling



large and domestic cats


Linkage to causative variant

VT
-
10 strains

VT for SF8 (nuclear export
signal)

VT lineages

VT
-
10 lineage

VT
-
4 lineage

VT
-
4 strains


VT
-
4 lineage = B allele/group

VT
-
15 & VT
-
8 lineages

VT
-
5 strains


Summary


Compiling list of all known influenza protein sequence features (
SFs
) in
IRD


Observed dramatic skewing in NS1 SFVT host distributions


In some cases, attributable to sampling biases


VT
-
1 and Avian H5N1 due to Asian sampling in mid
-
2000's


VT
-
2 and human due to 2009 pandemic H1N1


VT
-
11 and Other (Environment) in Delaware Bay



Performing multivariate statistical analysis to control for confounding
variables


In other cases, attributable to founder effects


VT
-
13 and
-
14 and
Viet Nam 2003


However, in other cases these explanations do not appears to be consistent
with the data, suggesting that these may indeed be NS1
-
mediated host
range restrictions


Equine VT
-
10 lineage


Avian VT
-
4 lineage (B allele/group)


Human VT
-
8 lineage


Human VT
-
15 lineage


Nuclear export
vs

linkage disequilibrium?

63


U.T. Southwestern


Richard Scheuermann


Burke Squires


Jyothi Noronha


Mengya Liu


Victoria Hunt


Shubhada Godbole


Brett Pickett


Ayman Al
-
Rawashdeh


MSSM


Adolfo Garcia
-
Sastre


Eric Bortz


Gina Conenello


Peter Palese


Vecna


Chris Larsen


Al Ramsey


LANL


Catherine Macken


Mira Dimitrijevic


U.C. Davis


Nicole Baumgarth


Northrop Grumman


Ed
Klem


Mike
Atassi


Kevin
Biersack


Jon Dietrich


Wenjie

Hua


Wei Jen


Sanjeev

Kumar


Xiaomei

Li


Zaigang

Liu


Jason Lucas


Michelle Lu


Bruce
Quesenberry


Barbara
Rotchford


Hongbo

Su


Bryan Walters


Jianjun

Wang


Sam
Zaremba


Liwei

Zhou


IRD SWG


Gillian Air, OMRF


Carol Cardona, Univ. Minnesota


Adolfo Garcia
-
Sastre
, Mt Sinai


Elodie

Ghedin
, Univ. Pittsburgh


Martha Nelson, Fogarty


Daniel Perez, Univ. Maryland


Gavin Smith, Duke Singapore


David Spiro, JCVI


Dave
Stallknecht
, Univ. Georgia


David
Topham
, Rochester


Richard Webby, St Jude


SFVT experts


Gillian Air, OMRF


Toru
Takimoto
, Rochester


Summer Galloway, Emory


Robert Lamb, Northwestern


Benjamin Hale, Mt. Sinai


USDA


David Suarez


Sage
Analytica


Robert Taylor


Lone
Simonsen


CEIRS Centers



Influenza SFVT Acknowledgments