Project Description HyPhy (www.hyphy.org) is a scriptable software platform designed to enable flexible and powerful analyses of DNA, RNA, codon, amino acid and other types of sequence data in an evolutionary context. Such analyses have become an indispensable component of most research studies that make use of comparative genomic data. Biologists and bioinformaticians increasingly recognize the benefits of molecular evolutionary analyses. Since its initial release in 2001, HyPhy has become a relatively stable and mature product, and has been downloaded by more than 4,500 unique users, integrated into several popular web-based genomic data analysis servers, cited in over 400 peer-reviewed publications and described in three book chapters, in spite of the fact that the development of the package has never been directly funded. This proposal seeks support to improve the quality, performance, reliability, modularity, documentation and feature sets of the HyPhy system.
Specific aims can be divided into four major areas: 1. Software engineering, testing, and documentation of the HyPhy codebase. 2. The development of a high-performance engine for phylogenetic maximum likelihood model fitting and inference. 3. Extension of a newly-initiated toolbox for machine learning applications in molecular evolution. 4. Creation and maintenance of a wiki-themed documentation resource.

Public Health Relevance

Project Narrative Molecular evolutionary analyses are central to many aspects of basic, translational, and applied biomedical research. Examples include identifying gene mutations that allow pathogens to evade the immune response;prediction of the structure and function of proteins;estimating the evolutionary relatedness of human or other populations;characterizing the magnitude of selective pressure, either natural or artificial, on genes or species.

Agency
National Institute of Health (NIH)
Institute
National Institute of General Medical Sciences (NIGMS)
Type
Research Project (R01)
Project #
5R01GM093939-04
Application #
8542870
Study Section
Special Emphasis Panel (ZRG1-BST-H (02))
Program Officer
Brazhnik, Paul
Project Start
2010-09-15
Project End
2014-08-31
Budget Start
2013-09-01
Budget End
2014-08-31
Support Year
4
Fiscal Year
2013
Total Cost
$265,099
Indirect Cost
$45,564
Name
North Carolina State University Raleigh
Department
Biostatistics & Other Math Sci
Type
Schools of Arts and Sciences
DUNS #
042092122
City
Raleigh
State
NC
Country
United States
Zip Code
27695
Frost, Simon D W; Magalis, Brittany Rife; Kosakovsky Pond, Sergei L (2018) Neutral Theory and Rapidly Evolving Viral Pathogens. Mol Biol Evol 35:1348-1354
Spielman, Stephanie J; Kosakovsky Pond, Sergei L (2018) Relative evolutionary rates in proteins are largely insensitive to the substitution model. Mol Biol Evol :
Pacheco, M AndreĆ­na; Matta, Nubia E; Valkiunas, Gediminas et al. (2018) Mode and Rate of Evolution of Haemosporidian Mitochondrial Genomes: Timing the Radiation of Avian Parasites. Mol Biol Evol 35:383-403
Shank, Stephen D; Weaver, Steven; Kosakovsky Pond, Sergei L (2018) phylotree.js - a JavaScript library for application development and interactive data visualization in phylogenetics. BMC Bioinformatics 19:276
Rife Magalis, Brittany; Kosakovsky Pond, Sergei L; Summers, Michael F et al. (2018) Evaluation of global HIV/SIV envelope gp120 RNA structure and evolution within and among infected hosts. Virus Evol 4:vey018
Weaver, Steven; Shank, Stephen D; Spielman, Stephanie J et al. (2018) Datamonkey 2.0: a modern web application for characterizing selective and other evolutionary processes. Mol Biol Evol :
Ragonnet-Cronin, Manon; Jackson, Celia; Bradley-Stewart, Amanda et al. (2018) Recent and Rapid Transmission of HIV Among People Who Inject Drugs in Scotland Revealed Through Phylogenetic Analysis. J Infect Dis 217:1875-1882
Spielman, Stephanie J; Kosakovsky Pond, Sergei L (2018) Relative evolutionary rate inference in HyPhy with LEISR. PeerJ 6:e4339
Kosakovsky Pond, Sergei L; Weaver, Steven; Leigh Brown, Andrew J et al. (2018) HIV-TRACE (TRAnsmission Cluster Engine): a Tool for Large Scale Molecular Epidemiology of HIV-1 and Other Rapidly Evolving Pathogens. Mol Biol Evol 35:1812-1819
Forrester, Naomi L; Wertheim, Joel O; Dugan, Vivian G et al. (2017) Evolution and spread of Venezuelan equine encephalitis complex alphavirus in the Americas. PLoS Negl Trop Dis 11:e0005693

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