We are interested in bioinformatics, molecular evolution, and molecular population genetics.

bioinfo_fig Genome projects are producing almost an infinite amount of molecular data. These genomic sequences present molecular information constructing current organisms. They are also the results of long molecular evolution since the origin of life. The genomic sequences are, therefore, filled with evolutionary footprints. Our interest revolves around mining such information from molecular sequence data.

In order to analyze information gleaned from genomic sequences, it is necessary to understand the rules of biochemistry and molecular biology. Understanding the mechanisms of molecular evolution and population genetics helps us to sift through superficial data and to incorporate another dimension in our study, i.e., time. Developing and incorporating new statistical and computational methods/tools needs to be emphasized to handle a large amount of data efficiently, and to extract biological information from highly noisy data.

Current Projects:


1) Classification of Seven Transmembrane Receptor (7TMR) superfamily. 7TMRs (as known as G-protein coupled receptor, GPCRs) form a large superfamily of proteins composed of six major classes and more than 30 subfamilies. They are integral membrane proteins characterized by seven membrane-spanning (transmembrane; TM) regions. They are involved with signal transduction across cell membranes. Many medically and pharmacologically important proteins are included in this superfamily (e.g., acetylcholine receptors, dopamine receptors, odorant receptors, etc.). Other than the structural similarity (7 TM regions), sequence similarity among different 7TMR groups is limited, and attempting to find new 7TMRs from new genomic data is often hindered due to such extreme diversity. To overcome this problem, we have been developing a new approach to detect weak similarity (reviewed in Moriyama and Kim, 2003; Moriyama and Opiyo, in press). Recently we have developed 7TMRmine Web server (Lu et al. 2009). It integrates 14 classifiers including both alignment-based and alignment-free methods. It can be easily applied for various transmembrane and other protein families.


2) Multiple alignment and phylogenetic tree reconstruction from GPCR and other extremely diverged protein families. Reconstructing a molecular phylogeny is most frequently the first step to understand the sequence evolution. In order to obtain phylogenies, good multiple alignments need to be generated. Many protein classification methods also rely on the quality of multiple alignments. Various algorithms are available for multiple alignments. However, none of them seem to be reliable when we have to deal with extremely diverged protein families, such as the GPCR super-family. Even its one member-family, the Olfactory receptor (Or) family, is extremely diverged (Moriyama et al. in preparation). It is not possible to reconstruct a phylogeny with any statistical confidence in such cases. At present, we are evaluating different multiple alignment algorithms applying for such diverged protein sequences. Our goal is to find a way to improve multiple alignments from Or and other GPCR protein sequences, and attempt to reconstruct more reliable phylogenies from such diverged sequences.

3) Gene mining and molecular evolutionary study on cytochrome b561 and related protein family (a collaboration with Han Asard Lab, Biochemistry). Cytochrome b561 (cyt b561) is an integral membrane protein containing six TM regions and a pair of hemes. This protein family involves in the transmembrane electron transport using ascorbate as an electron donor. Some of the related proteins contain a region similar to cyt b561 (cyt b561 domain) as well as another domains (e.g., dopamine b-hydroxylase homology domain: DoH). Their extreme sequence divergence, similar to the GPCR super-family, and a network of relationships among different functional domains make this protein family extremely interesting, but also a challenge, to study. We are currently attempting to search the cyt b561 related proteins as many as possible from several genomic sequences (e.g., Arabidopsis thaliana, mouse). By conducting both molecular evolutionary and functional studies on this diverged protein family, we hope to understand the intriguing mode of protein evolution in detail. It involves with repeated domain shuffling and functional acquisition.

4) Development of a genome database system to facilitate gene prediction from fungal genomic data. (a collaboration with Steven Harris Lab, Plant Science Initiative/Plant Pathology). Fungal Genome Initiative (Whitehead Institute/MIT Center for Genome Research, 2002) proposed to sequence 15 complete fungal genomes. Therefore, we expect to see a rapid increase of fungal genomic data in the near future. On the other hand, since completion of the Saccharomyces cerevisiae genome became a landmark in genomics in 1996, only a handful of fungal genomic data has become available (e.g., the fission yeast Schizosaccharomyces pombe, the filamentous fungus Neurospora crassa). This scarcity of fungal genomic data creates a difficult situation in fungal genome projects, since in order to optimize the gene-mining power, organism-specific gene and genomic information is necessary. We are planning to develop fungal specific genomic database system that incorporates genomic analysis tools and their results, and to develop codon_fig a gene mining system specifically optimized for fungal genomes.

5) Synonymous codon usage bias. Nucleotide substitutions between synonymous codons do not change amino acids. However in many organisms, they do not seem to be neutral to natural selection. Rather they are under a weak selection. Large variations in codon usage bias have been found among genes within the same genome. It can vary also between different regions along the gene, as well as between homologous genes from different species (reviewed in Moriyama, 2003). While this quantity, as well as base composition, has become one of the most routinely obtained information from genomic sequences, it has not been well-understood and has been under-utilized in genomic analyses. One of our goals is to incorporate such information in bioinformatics tools and achieve thorough and multi-dimensional understanding of genomic data.

Recent Publications:

Maudhoo, M. D., Ren, D. Gradnigo, J. S., Gibbs, R. M., Lubker, A. C., Moriyama, E. N., French, J. A., and Norgren Jr, .R. B. (2014) De novo assembly of the common marmoset transcriptome from NextGen mRNA sequences. GigaScience 3: 14 (PMCID: 4169894)

Eyun, S.-I., Wang, H., Pauchet, Y., Ffrench-Constant, R.H., Benson, A.K., Valencia-Jiménez, A., Moriyama, E.N., and Siegfried, B.D. (2014) Molecular evolution of glycoside hydrolase genes in the western corn rootworm (Diabrotica virgifera virgifera). PLoS One 9: e94052 (PMCID: 3981738) — Supplemental materials

Yamasaki, T., Voshall, A., Kim, E.-J., Moriyama, E. N., Cerutti, H., and Ohama T. (2013) Complementarity to a miRNA seed region is sufficient to induce moderate repression of a target transcript in the unicellular green alga Chlamydomonas reinhardtii. The Plant Journal 76: 1045-1056 (PMID: 24127635)

Zheng, X. and Moriyama, E. N. (2013) Comparative studies of differential gene calling using RNA-Seq data. BMC Bioinformatics 14: S7 (PMCID: 3891352)

Shah, N., Gaupp, R., Moriyama, H., Eskridge, K. M., Moriyama, E. N.*, and Somerville, G. A.* (2013) Reductive evolution and the loss of PDC/PAS domains from the genus Staphylococcus. BMC Genomics 14: 524 (PMCID: 3284338)

Deng, B., Hinds, B., Zheng, X., and Moriyama, E. N. (2013) Bioinformatic game theory and its application to biological affinity networks. Applied Mathematics 4: 92-108.

Ma, X., Kim, E.-J., Kook, I., Ma, F., Voshall, A., Moriyama, E. N., and Cerutti, H. (2013) Small interfering RNA-mediated translation repression alters ribosome sensitivity to inhibition by cycloheximide in Chlamydomonas reinhardtii. Plant Cell 25: 985-998 (PMCID: 3634701)

Wilson, R. A., Fernandez, J., Quispe, C. F., Gradnigo, J., Seng, A., Moriyama, E. N., and Wright, J. D. (2012) Towards defining nutrient conditions encountered by the rice blast fungus during host infection. PLoS ONE 7: e47392 (PMCID: 3468542)

Shah, N., Dorer, D. R., Moriyama, E. N., and Christensen, A. C. (2012) Evolution of a large, conserved and syntenic gene family in insects. G3: Genes, Genomes, Genetics 2: 313-319 (PMCID: 3284338) — Supplemental materials

Klopffleisch, K., Phan, N., Augustin, K., Bayne, R. S., Booker, K. S., Botella, J. R., Carpita, N. C., Carr, T., Chen, J.-G., Cooke, T. R., Frick-Cheng, A., Friedman, E. J., Fulk, B., Hahn, M. G., Jiang, K., Jorda, L., Kruppe, L., Liu, C., Lorek, J., McCann, M. C., Molina, A., Moriyama, E. N., Mukhtar, M. S., Mudgil, Y., Pattathil, S., Schwarz, J., Seta, S., Tan, M., Temp, U., Trusov, Y., Urano, D., Welter, B., Yang, J., Panstruga, R., Uhrig, J. F. and Jones, A. M. (2011) Arabidopsis G protein interactome reveals connections to cell wall carbohydrates and morphogenesis. Molecular Systems Biology 7: 532 (PMCID: 3202803) — AGIdb: Arabidopsis G-signaling Interactome Database

Anderson, C. L., Strope, C. L., and Moriyama, E. N. (2011) Assessing multiple sequence alignments using visual tools.
In Bioinformatics: Trends and Methodologies (ed. Mahdavi, M. A.) InTech (ISBN 978-953-307-282-1)
Supplemental files

Anderson, C. L., Strope, C. L. and Moriyama, E. N. (2011) SuiteMSA: Visual tools for multiple sequence alignment comparison and molecular sequence simulation. BMC Bioinformatics 12: 184 (PMCID: 3133551) — SuiteMSA website

Strope, P. K., Nickerson, K. W., Harris, S. D. and Moriyama, E. N. (2011) Molecular evolution of urea amidolyase and urea carboxylase in fungi. BMC Evolutionary Biology 11: 80 (PMCID: 3073912)

Opiyo, S. O., Pardy, R. L., Moriyama, H. and Moriyama, E. N. (2010) Evolution of the Kdo2-lipid A biosynthesis in bacteria. BMC Evolutionary Biology 10: 362 (PMCID: 3087551)

Benson, A. K., Kelly, S. A., Legge, R., Ma, F., Low, S. J., Kim, J., Zhang, M., Oh, P. L., Nehrenberg, D., Hua, K., Kachman, S. D., Moriyama, E. N., Walter, J., Peterson, D. A. and Pomp, D. (2010) Individuality in gut microbiota composition is a complex, polygenic trait shaped by multiple environmental and host genetic factors. Proc Natl Acad Sci USA 107: 18933-18938 (Published online before print October 11, 2010, doi: 10.1073/pnas.1007028107) (PMCID: 2973891)

Moriyama, E. N., Scott, S. D., and Soh, L.-K. (2010) Editorial Int. J. Bioinformatics Research and Applications 6 (Guest Editors for Special Issue: Biotechnology and Bioinformatics Symposium (BIOT-2009))

Prokupek, A. M., Eyun, S.-I., Ko, L., Moriyama, E. N., and Harshman, L. G. (2010) Molecular evolutionary analysis of seminal receptacle sperm storage organ genes of Drosophila melanogaster. Journal of Evolutionary Biology 23: 1386-1398 (PMID: 20500366) — the project home page

Opiyo, S. O. and Moriyama, E. N. (2010) Mining Cytochrome b561 from plant genomes. Int. J. Bioinformatics Research and Applications 6: 209-221 (Special Issue: Biotechnology and Bioinformatics Symposium: BIOT-08)Supplementary tables — (PMCID: 2846449)

Oh, P. L., Benson, A. K., Peterson, D. A., Patil, P. B., Moriyama, E. N., Roos, S., and Walter, J. (2010) Diversification of the gut symbiont Lactobacillus reuteri as a result of host-driven evolution. ISME Journal 4: 377-387 (Advanced Access published in 11/2009; doi: 10.1038/ismej.2009.123) (PMID: 19924154)

Moriyama, E. N. and Opiyo, S. O. (2010) Bioinformatics of Seven-Transmembrane Receptors in Plant Genomes. Pp. 251-277 in Yalovsky, S., Baluska, F., and Jones, A. eds. Integrated G Proteins Signaling in Plants, Springer-Verlag, Berlin Heidelberg.

Strope, C. L., Abel, K., Scott, S. D., and Moriyama, E. N. (2009) Biological sequence simulation for testing complex evolutionary hypotheses: indel-Seq-Gen version 2.0. Mol Biol Evol 26: 2581-2593 (Advanced Access published in 08/2009; doi: 10.1093/molbev/msp174) (PMCID: 2760465) — indel-Seq-Gen website

Lu, G., Wang, Z., Jones, A. M., and Moriyama, E. N. (2009) 7TMRmine: A Web server for hierarchical mining of 7TMR proteins. BMC Genomics 10: 275 (PMCID: 2718930) — 7TMRmine website &mdash

Martínez, I., Wallace, G., Zhang, C., Legge, R., Benson, A. K., Carr, T. P., Moriyama, E. N., and Walter, J. (2009) Diet-induced metabolic improvements in a hamster model of hypercholesterolemia are strongly linked to alterations of the gut microbiota. Applied and Environmental Microbiology 75: 4175-4184 (PMCID: 2698331)

Opiyo, S. O. and Moriyama, E. N. (2009) Mining the Arabidopsis and rice genomes for cyclophilin protein families. Int. J. Bioinformatics Research and Applications 5: 295-309 (Special Issue: Biotechnology and Bioinformatics Symposium (BIOT-07)) (PMCID: 2697455) — Supplementary tables

Prokupek, A., Hoffmann, F., Eyun, S. I., Moriyama, E., Zhou, M. and Harshman, L. (2008) An evolutionary expressed sequence tag analysis of Drosophila spermatheca genes: protein evolution and identity. Evolution 62: 2936-2947 (PMID: 18752616) — the project home page

Veerappan, C. S., Avramova, Z. and Moriyama, E. N. (2008) Evolution of SET-domain protein families in the unicellular and multicellular Ascomycota fungi. BMC Evolutionary Biology 8: 190 (doi:10.1186/1471-2148-8-190) (PMCID: 2474616)

Vicario, S., Moriyama, E. N. and Powell, J. R. (2007) Codon usage in twelve species of Drosophila. BMC Evolutionary Biology 7: 226 (PMCID: 2213667)

Johnston, C. A., Temple, B. R., Chen, J.-G., Gao, Y., Moriyama, E. N., Jones, A. M., Siderovski, D. P. and Willard, F. S. (2007) Comment on "A G protein-coupled receptor is a plasma membrane receptor for the plant hormone abscisic acid". Science 318: 914 (PMID: 17991845)

Strope, P. K. and Moriyama, E. N. (2007) Simple alignment-free methods for protein classification: a case study from G-protein coupled receptors. Genomics 89: 602-612 (doi: 10.1016/j.ygeno.2007.01.008) (PMID: 17336495)
— Supplementary data (Figure, Tables, Datasets used) —

Xia, X., Huang, H., Carullo, M., Betran, E., and Moriyama, E. N. (2007) Conflict between translation initiation and elongation in vertebrate mitochondrial genomes. PLoS ONE 2: e227 (doi:10.1371/journal.pone.0000227) (PMCID: 1794132)

Strope, C. L., Scott, S. D. and Moriyama, E. N. (2007) indel-Seq-Gen: a new protein family simulator incorporating domains, motifs, and indels. Mol Biol Evol 24: 640-649 (Advanced Access published in 12/2006; doi: 10.1093/molbev/msl195) (PMID: 17158778) — Preprint PDF file, Supplementary files, indel-Seq-Gen Web site

Opiyo, S. O. and Moriyama, E. N. (2007) Protein family classification with partial least squares. J Proteome Res 6: 846-853 (Web released in 12/2006, doi: 10.1021/pr060534k) (PMID: 17269741) — Supplementary Tables

Moriyama, E. N.*, Strope, P. K., Opiyo, S. O., Chen, Z. and Jones, A. M. (2006) Mining the Arabidopsis thaliana genome for highly-divergent seven transmembrane receptors. Genome Biology 7: R96 (PMCID: 1794564) — Supplementary Materials

Lu, G., Jiang, L., Kotalik, R. M., Rowley, T. W., Zhang, L., Chen, X. J., and Moriyama, E. N. (2006) GenomeBlast: a web tool for small genome comparison. BMC Bioinformatics 7: S18 (PMCID: 1780113) — GenomeBlast web

Moriyama, E. N. and J. Kim. (2005) Protein family classification with discriminant function analysis. Pp. 121-132 in Gustafson, J. P., Shoemaker, R. and Snape, J. W. eds. Genome Exploitation: Data Mining the Genome. Springer, New York. (preprint PDF file)

Simbahan, J., Kurth, E., Schelert, J., Moriyama, E. N., Jovanovich, S. and Blum, P. (2005) Community analysis of a mercury hotspring support domain-specific forms of 3 mercuric reductase. Appl Environ Microbiol 71: 8836-8845 (PMCID: 1317467)

Lu, G. and E. N. Moriyama (2004) Vector NTI, a balanced all-in-one sequence analysis suite. Briefings in Bioinformatics 5: 1-11 (PMID: 15606974)

Sainz, A. C., L. V. Mauro, E. N. Moriyama, and B. A. García (2004) Phylogeny of triatomine vectors of Trypanosoma cruzi suggested by mitochondrial DNA sequences. Genetica 121: 229-240 (PMID: 15521421)

Powell, J. R., E. Sezzi, E. N. Moriyama, J. M. Gleason and A. Caccone (2003) Analysis of a shift in codon usage in Drosophila. J Mol Evol, 57: S214-S225 (PMID: 15008418)

Dorer, D.R., J. A. Rudnick, E. N. Moriyama and A. C. Christensen (2003) A family of genes clustered at the Triplo-lethal locus of Drosophila melanogaster has an unusual evolutionary history and significant synteny with Anopheles gambiae. Genetics, 165: 613-621 (PMCID: 1462804)

Moriyama, E. N. (2003) Codon Usage. in Cooper, D. N. ed. Nature Encyclopedia of the Human Genome. Nature Publishing Group, Macmillan Publishers Ltd, London. (preprint PDF file)

García, B. A., E. N. Moriyama and J. R. Powell (2001) Mitochondrial DNA sequences of Triatomines (Hemiptera: Reduviidae): Phylogenetic relationships. J Med Entomol 38: 675-683 (PMID: 11580040)

Kim, J., E. N. Moriyama, C. G. Warr, P. J. Clyne and J. R. Carlson (2000) Identification of novel multi-transmembrane proteins from genomic databases using quasi-periodic structural properties. Bioinformatics 16: 767-775 (PMID: 11108699)

Caccone, A., B. A. García, K. D. Mathiopoulos, G.-S. Min, E. N. Moriyama and J. R. Powell (1999) Characterization of the soluble guanylyl cyclase b-subunit gene in the mosquito Anopheles gambiae. Insect Mol Biol 8: 23-30 (PMID: 9927171)

Moriyama, E. N., D. A. Petrov and D. L. Hartl (1998) Genome size and intron size in Drosophila. Mol Biol Evol 15: 770-773 (PMID: 9615458)

Moriyama, E. N. and J. R. Powell (1998) Gene length and codon usage bias in Drosophila melanogaster, Saccharomyces cerevisiae and Escherichia coli. Nucleic Acids Res 26: 3188-3193 (PMCID: 147681)

Moriyama, E. N. and J. R. Powell (1998) Scientific Correspondence. Nucleic Acids Res 26: 4540 (PMCID: 147868)

Moriyama, E. N. and J. R. Powell (1997) Codon usage bias and tRNA abundance in Drosophila. J Mol Evol 45: 514-523 (PMID: 9342399)

Moriyama, E. N. and J. R. Powell (1997) Synonymous substitution rates of Drosophila: mitochondrial versus nuclear genes. J Mol Evol 45: 378-391 (PMID: 9321417)

Powell, J. R. and E. N. Moriyama (1997) Evolution of codon usage bias in Drosophila. Proc Natl Acad Sci USA 94: 7784-7790 (PMCID: 33704)

Gleason, J. M., A. Caccone, E. N. Moriyama, K. P. White and J. R. Powell (1997) Mitochondrial DNA phylogenies for the Drosophila obscura group. Evolution 51: 433-440.

Moriyama, E. N. and J. R. Powell (1996) Intraspecific nuclear DNA variation in Drosophila. Mol Biol Evol 13: 261-277 (PMID: 8583899)

Caccone, A., E. N. Moriyama, J. M. Gleason, L. Nigro and J. R. Powell (1996) A molecular phylogeny for the Drosophila melanogaster subgroup and the problem of polymorphism data. Mol Biol Evol 13: 1224-1232 (PMID: 8896375)

Nurminsky, D. I., E. N. Moriyama, E. R. Lozovskaya and D. L. Hartl (1996) Molecular phylogeny and genome evolution in the Drosophila virilis species group: duplications of the alcohol dehydrogenase gene. Mol Biol Evol 13: 132-149 (PMID: 8583887)

Fushitani, K., K. Higashiyama, E. N. Moriyama, K. Imai and K. Hosokawa (1996) The amino acid sequences of two a chains of hemoglobins from Komodo dragon Varanus komodoensis and phylogenetic relationships of amniotes. Mol Biol Evol 13: 1039-1043 (PMID: 8752011)

Lohe, A. R., E. N. Moriyama, D.-A. Lidholm and D. L. Hartl (1995) Horizontal transmission, vertical inactivation, and stochastic loss of Mariner-like transposable elements. Mol Biol Evol 12: 62-72 (PMID: 7877497)

Hartl, D. L., E. N. Moriyama and S. A. Sawyer (1994) Selection intensity for codon bias. Genetics 138: 227-234 (PMCID: 1206133)

Moriyama, E. N. and D. L. Hartl (1993) Codon usage bias and base composition of nuclear genes in Drosophila. Genetics 135: 847-858 (PMCID: 1205521)

Graduate Student Dissertations and Theses:

Ximeng Zheng (2012) Comparative studies of differential gene calling methods for RNA-Seq data. MS thesis, School of Biological Sciences, University of Nebraska—Lincoln (PDF file)

Pooja K. Strope (2011) Functional classi cation of divergent protein sequences and molecular evolution of multi-domain proteins. PhD dissertation, School of Biological Sciences, University of Nebraska—Lincoln (PDF file)

Jason C. Macrander (2010) Microsatellite development, population structure and demographic histories for two species of Amazonian peacock bass Cichla temensis and Cichla monoculus (Perciformes: Cichlidae). MS thesis, School of Biological Sciences, University of Nebraska—Lincoln (PDF file)

Cory L. Strope (2009) Evaluating indels as characters of biological informativeness. PhD dissertation, Department of Computer Science and Engineering, University of Nebraska—Lincoln (PDF file: 28.4MB)

Stephen O. Opiyo (2007) Protein family classification using multivariate methods. PhD dissertation, Department of Agronomy, University of Nebraska—Lincoln (PDF file)

Chendhore S. Veerappan (2007) Molecular evolution of SET-domain protein families in eukaryotes. MS thesis, School of Biological Sciences, University of Nebraska—Lincoln (PDF file)

Mamta Bajaj (2007) Structural analysis of deoxyuridine triphosphatase from Arabidopsis thaliana. MS thesis, School of Biological Sciences, University of Nebraska—Lincoln (PDF file)

Mamta Bajaj (2005) Development of a prediction method for amphipathic alpha-helices from protein primary structure. MS thesis, Department of Computer Science and Engineering, University of Nebraska—Lincoln (PDF file)

Pooja Khati (2004) Comparative analysis of protein classification methods. MS thesis, Department of Computer Science and Engineering, University of Nebraska—Lincoln (PDF file)

Skanth Ganesan (2004) Comparative analysis of gene prediction methods and development of a fungal genome database system. MS thesis, Department of Computer Science and Engineering, University of Nebraska—Lincoln (PDF file)

Zhifang Wang (2002) Development of a hierarchical protein classification tool. MS project report, Department of Computer Science and Engineering, University of Nebraska—Lincoln (PDF file)

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(updated: October 10, 2014)

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