Avian Flu Bioinformatics NS-1 Motif analysis - Fgamedia.org

websterhissΒιοτεχνολογία

1 Οκτ 2013 (πριν από 3 χρόνια και 10 μήνες)

77 εμφανίσεις

Avian Flu Bioinformatics NS
-
1 Motif analysis


In this exercise we will examine the NS
-
1 gene, using full coding sequence data
sets, to determine the identity of the last four amino acids. Research has
indicated that this PL motif can be used to make a dete
rmination as to the host /
source of an influenza strain.
Large
-
Scale Sequence Analysis of Avian
Influenza Isolates


http://
www.sciencemag.org/

SCIENCE VOL 311 17
MARCH 2006
.
In this research, analysis of the NS
-
1 AA coding sequence showed
the following motifs associated with avian, human, and swine influenzas:


EPEV, ESEV
-

mostly avian

GPEV, GPKV
-

mostly swine

RPKV, RSKV
-

mostly human

KSEV
-

Spanish influenza of 1918


In human flu:
The (PL signature) motifs

for highly pathogenic human infections
are below. So maybe we can comment on the binding studies of these signature
motifs to the PDZ domain of the protein Disheveled (Dsh):


GSESEV (2003)


Avian influenza


strong binding, influenza is lethal

GSEPEV (1
997)


Avian influenza
-

strong binding, influenza is lethal

GSKSEV (1918)


Avian influenza


very strong binding, influenza is very lethal

GSRSKV (low pathogenic)


human



binding is moderate, influenza is moderate


Now let’s look at the codons for G, K
, E and R


G (Glycine)

K (Lysine)

E (Glutamic Acid)

R Arginine

CGT

AAA

GAA

CGU

CGC

AAG

GAG

CGC

GGA

E => K

GAA

CGA

GGG


GAG

CGG


The distance from E=> K is one letter

The distance from E=> G is one letter

The distance from R=> G is one letter in the wo
bble base


The distance from R to K is large (human to bird, hence the bird
-
to
-
bird mutation
of one letter E to K was most likely as the source of the 1918 Influenza pandemic.
Analysis
of the influenza pandemic of 1957 H
2
N
2

and the influenza pandemic of
19
68 H
3
N
2

was a human influenza. Below are 25 accession numbers representing
the sequences and PL motifs that we are following through time and host.


H1N1 TIKSEV


A / Brevig Mission 1918 (human)
AF333238

H1N1 TIRSEV


Puerto Rico 1934 (human)
AF389122

H2N2 TIRSEV


Leningrad 1957(human)
M81578

H1N1 TIRSEV
-

Leningrad 1954 (human)
X52146

H3N2 TIRS
KV
-

Aiche 1968 (human)
M35094


H3N2 TIRSKV
-

England 1969 (human)
AJ298949

H3N2 TIRSKV
-

Hong Kong 1973 (human)
CY009008

H1N1 TIRSKV Chili 1983 X15282 (human)
X15282

H3N2 TARSKV


Memphis 1995 (human)
CY002276

H1N1 TIRSEV


Taiwan 1996 (huma
n)
AF055423

H5N1 TIEPEV


Hong Kong 1997 (human)
AF036360

H3N2 TARSKV


Hong Kong 1997 (human)
AF256182

H3N2 TARSKV


New York 1998 (human)
CY001497

H5N1 TIESKV


Mongolia 2005 (goose)
AB239306


H3N2 TARSKV


New York 1999 (human)
CY001780

H3N2 TARSKV
-

New York 2000 (human)
CY00046
9

H3N2 TIRSEV


New York 2001 (human)
CY001956

H3N2 TARSEV


New York 2002 (human)
CY000589

H3N2 TARSKV


New York 2003 (human)
CY000905

H1N2 TARSKV


New York 2003 (human)
CY002356

H3N2 TARSKV


New York 2004 (human)
CY003076

H3N2 TARSK
V


New York 2005 (human)
CY002012

H3N2 TIRSEV


Influenza X
-

A virus 2003
AB036777


Lab exercises:


1.

BLAST Exercise


follow the changes in these motifs by BLASTing the protein
database using the protein sequence from any of these accession numbers.

2.

Sequence exercise


go to
http://www.ncbi.nlm.nih.gov/genomes/FLU/FLU.html

and search for sequences by year, subtype (serotype) or segment of the genome.

3.

Sequence exercise


go to
http://flu.lanl.gov/

a
nd repeat the exercise above.

4.

Alignment exercise


use the alignment tools at each of the above databases.

5.

Practice using the ‘saved search and experiments’, make sure to ‘read the readme’


Questions:


1.

How long does the TIRSEV motif persist in any of the H
xNy serotypes?

2.

When does the TIESEV / TIEPEV (avian) motif appear again in a flu data set?

3.

Can you start to see the ‘mixing of motifs’ described in ‘recombinomics’?