The human genome and other sequencing projects have now produced vast amounts of DNA sequence data from nuclear and mitochondrial genomes of diverse organisms. In order to generate a deeper understanding of genome evolution and gene function using this data, easy-to-use general-purpose computational tools for large-scale data analysis and new statistical/computational methods are needed. Therefore, the main objective of the proposed work is to develop the Molecular Evolutionary Genetics Analysis Professional software (called MEGA-PRO) for exploring, discovering and analyzing DNA and protein sequence variation in the context of protein structure. We plan to develop MEGA-PRO to support (i) functional genomics analysis of DNA and protein sequence variation among species and genes of multigene families and (ii) exploration of results from evolutionary analysis in a protein structural context. In MEGA-PRO, we will extend the repertoire of methods for molecular phylogenetics, evolutionary, and genomic analysis for evolutionary estimation and hypothesis testing. To address the specific needs of individual investigators, groups of investigators, and students, MEGA-PRO will be developed as a single-source solution to facilitate web-enabled analysis (in addition to the standalone desktop application) and will include facility for scripting to enable automated large-scale analyses. In addition to the proposed technological developments, many new algorithms and statistical methods need to be developed to estimate evolutionary parameters and test hypotheses when using a large number of genes and for large-scale data analysis. Therefore, we propose a project that integrates research and tool development in a multidisciplinary effort. Main goals of the research in statistical and computational methods involve (i) estimation of genomic distances and mutation rates (ii)tests of equality of mutation/substitution rate among genes and species and other fundamental assumptions used in comparative sequence analysis, and (iii) investigation of phylogentic inference methodologies for datasets containing a large number of genes with partial species overlaps. As always, MEGA-PRO programs will be made available free of charge for all uses, including research, education, and training.

Agency
National Institute of Health (NIH)
Institute
National Human Genome Research Institute (NHGRI)
Type
Research Project (R01)
Project #
5R01HG002096-06
Application #
7025758
Study Section
Genome Study Section (GNM)
Program Officer
Brooks, Lisa
Project Start
2000-01-01
Project End
2007-04-30
Budget Start
2006-03-01
Budget End
2007-04-30
Support Year
6
Fiscal Year
2006
Total Cost
$254,352
Indirect Cost
Name
Arizona State University-Tempe Campus
Department
Other Basic Sciences
Type
Schools of Arts and Sciences
DUNS #
943360412
City
Tempe
State
AZ
Country
United States
Zip Code
85287
Katsura, Yukako; Stanley Jr, Craig E; Kumar, Sudhir et al. (2017) The Reliability and Stability of an Inferred Phylogenetic Tree from Empirical Data. Mol Biol Evol 34:718-723
Karim, Sajjad; NourEldin, Hend Fakhri; Abusamra, Heba et al. (2016) e-GRASP: an integrated evolutionary and GRASP resource for exploring disease associations. BMC Genomics 17:770
Liu, Li; Tamura, Koichiro; Sanderford, Maxwell et al. (2016) A Molecular Evolutionary Reference for the Human Variome. Mol Biol Evol 33:245-54
Miura, Sayaka; Tate, Stephanie; Kumar, Sudhir (2015) Using Disease-Associated Coding Sequence Variation to Investigate Functional Compensation by Human Paralogous Proteins. Evol Bioinform Online 11:245-51
Kumar, Avishek; Butler, Brandon M; Kumar, Sudhir et al. (2015) Integration of structural dynamics and molecular evolution via protein interaction networks: a new era in genomic medicine. Curr Opin Struct Biol 35:135-42
Butler, Brandon M; Gerek, Z Nevin; Kumar, Sudhir et al. (2015) Conformational dynamics of nonsynonymous variants at protein interfaces reveals disease association. Proteins 83:428-35
Filipski, Alan; Tamura, Koichiro; Billing-Ross, Paul et al. (2015) Phylogenetic placement of metagenomic reads using the minimum evolution principle. BMC Genomics 16 Suppl 1:S13
Battistuzzi, Fabia U; Billing-Ross, Paul; Murillo, Oscar et al. (2015) A Protocol for Diagnosing the Effect of Calibration Priors on Posterior Time Estimates: A Case Study for the Cambrian Explosion of Animal Phyla. Mol Biol Evol 32:1907-12
Gerek, Nevin Z; Liu, Li; Gerold, Kristyn et al. (2015) Evolutionary Diagnosis of non-synonymous variants involved in differential drug response. BMC Med Genomics 8 Suppl 1:S6
Hedges, S Blair; Marin, Julie; Suleski, Michael et al. (2015) Tree of life reveals clock-like speciation and diversification. Mol Biol Evol 32:835-45

Showing the most recent 10 out of 48 publications