63 research outputs found
Identification of human-to-human transmissibility factors in PB2 proteins of influenza A by large-scale mutual information analysis
<p>Abstract</p> <p>Background</p> <p>The identification of mutations that confer unique properties to a pathogen, such as host range, is of fundamental importance in the fight against disease. This paper describes a novel method for identifying amino acid sites that distinguish specific sets of protein sequences, by comparative analysis of matched alignments. The use of mutual information to identify distinctive residues responsible for functional variants makes this approach highly suitable for analyzing large sets of sequences. To support mutual information analysis, we developed the AVANA software, which utilizes sequence annotations to select sets for comparison, according to user-specified criteria. The method presented was applied to an analysis of influenza A PB2 protein sequences, with the objective of identifying the components of adaptation to human-to-human transmission, and reconstructing the mutation history of these components.</p> <p>Results</p> <p>We compared over 3,000 PB2 protein sequences of human-transmissible and avian isolates, to produce a catalogue of sites involved in adaptation to human-to-human transmission. This analysis identified 17 characteristic sites, five of which have been present in human-transmissible strains since the 1918 Spanish flu pandemic. Sixteen of these sites are located in functional domains, suggesting they may play functional roles in host-range specificity. The catalogue of characteristic sites was used to derive sequence signatures from historical isolates. These signatures, arranged in chronological order, reveal an evolutionary timeline for the adaptation of the PB2 protein to human hosts.</p> <p>Conclusion</p> <p>By providing the most complete elucidation to date of the functional components participating in PB2 protein adaptation to humans, this study demonstrates that mutual information is a powerful tool for comparative characterization of sequence sets. In addition to confirming previously reported findings, several novel characteristic sites within PB2 are reported. Sequence signatures generated using the characteristic sites catalogue characterize concisely the adaptation characteristics of individual isolates. Evolutionary timelines derived from signatures of early human influenza isolates suggest that characteristic variants emerged rapidly, and remained remarkably stable through subsequent pandemics. In addition, the signatures of human-infecting H5N1 isolates suggest that this avian subtype has low pandemic potential at present, although it presents more human adaptation components than most avian subtypes.</p
Institutional and/versus commercial media coverage: representations of the University of California, Berkeley–Novartis agreement
EPIMHC: a curated database of MHC-binding peptides for customized computational vaccinology
EPIMHC is a relational database of MHC-binding peptides and T cell epitopes that are observed in real proteins. Currently, the database contains 4867 distinct peptide sequences from various sources, including 84 tumor-associated antigens. The EPIMHC database is accessible through a web server that has been designed to facilitate research in computational vaccinology. Importantly, peptides resulting from a query can be selected to derive specific motif-matrices. Subsequently, these motif-matrices can be used in combination with a dynamic algorithm for predicting MHC-binding peptides from user-provided protein queries. AVAILABILITY: The EPIMHC database server is hosted by the Dana-Farber Cancer Institute at the site http://immunax.dfci.harvard.edu/bioinformatics/epimhc
The Effectiveness of Altruistic Appeals and Pregiving in an Antisocial Compliance-Gaining Situation
Account Strategies for the Violation of Social Norms: Integration and Extension of Sociological and Social Psychological Typologies
The Form and Function of Remedial Moves: Reported Use, Psychological Reality and Perceived Effectiveness
Attending to attention: How do people attract, manage, and negotiate attention using mobile devices?
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