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New paper #61: Computational screen to identify important mutations in influenza

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We're happy to announce a new Pande Group paper (paper #61 at http://folding.stanford.edu/English/Papers).  This paper describes a new computational screen to identify important mutations in influenza:

 

Functionally Important Residues in Influenza Hemagglutinin. 

Peter M. Kasson and Vijay S. Pande. Pacific Symposium on Biocomputing

14:492-503(2009). 

Download URL:

 

The influenza hemagglutinin protein performs several important

functions, including attaching the virus to cells it will infect and

releasing the viral genome into the interior of the cell. Most

protective antibodies against influenza also bind to the hemagglutinin

protein. We wish to understand how mutations to hemagglutinin affect

viral function, including what keeps avian influenza ("bird flu") from

being readily transmissible between humans. In this paper, we have

applied a technique from information theory known as mutual

information to genetic sequence data to predict important mutation

sites on the hemagglutinin protein. In follow-up work, we are

combining this technique with other methods to refine these

predictions and test some of them using Folding@Home. 

 

PS For those curious out in more details, check out the paper (see link above) or the technical abstract:

Influenza hemagglutinin mediates both cell-surface binding and cell

entry by the virus. Mutations to hemagglutinin are thus critical in

determining host species specificity and viral infectivity. Previous

approaches have primarily considered point mutations and sequence

conservation; here we develop a complementary approach using mutual

information to examine concerted mutations. For hemagglutinin,

several overlapping selective pressures can cause such concerted

mutations, including the host immune response, ligand recognition and

host specificity, and functional requirements for pH-induced

activation and membrane fusion. Using sequence mutual information as

a metric, we extracted clusters of concerted mutation sites and

analyzed them in the context of crystallographic data. Comparison of

influenza isolates from two subtypes—human H3N2 strains and human and

avian H5N1 strains—yielded substantial differences in spatial

localization of the clustered residues. We hypothesize that the

clusters on the globular head of H3N2 hemagglutinin may relate to

antibody recognition (as many protective antibodies are known to bind

in that region), while the clusters in common to H3N2 and H5N1

hemagglutinin may indicate shared functional roles. We propose that

these shared sites may be particularly fruitful for mutagenesis

studies in understanding the infectivity of this common human

pathogen. The combination of sequence mutual information and

structural analysis thus helps generate novel functional hypotheses

that would not be apparent via either method alone.

 

 

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en fait l' influenza est le virus de la grippe _

 

les travaux avec F@H deviennent de plus en plus variés , ce qui en montre bien l' interet .

 

je crois que les critiques envers le projet vont devenir de plus en plus rares :(

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