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

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:

Combining Mutual Information with Structural Analysis to Screen for Functionally Important Residues in Influenza Hemagglutinin. 
Peter M. Kasson and Vijay S. Pande. Pacific Symposium on Biocomputing 14:492-503(2009). 
Download URL: http://psb.stanford.edu/psb-online/proceedings/psb09/kasson.pdf  

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.

Comments

[Ivoshiee]

What projects (if any) that paper is based on?

[toTOW]

Judging by project descriptions, I'd say that most of the SMP projects are involved : p265x (global viruses study) and p2662 to 2675 (influenza virus study).