Genetics and Genomics Commons^™

Promoting Synergistic Research And Education In Genomics And Bioinformatics, Jack Y. Yang, Mary Qu Yang, Hamid R. Arabnia, Youping Deng

Faculty Publications

Bioinformatics and Genomics are closely related disciplines that hold great promises for the advancement of research and development in complex biomedical systems, as well as public health, drug design, comparative genomics, personalized medicine and so on. Research and development in these two important areas are impacting the science and technology.

High throughput sequencing and molecular imaging technologies marked the beginning of a new era for modern translational medicine and personalized healthcare. The impact of having the human sequence and personalized digital images in hand has also created tremendous demands of developing powerful supercomputing, statistical learning and artificial intelligence approaches to …

Investigation Of Transmembrane Proteins Using A Computational Approach, Jack Y. Yang, Mary Qu Yang, Keith A. Dunker, Youping Deng, Xudong Huang

Faculty Publications

Background

An important subfamily of membrane proteins are the transmembrane α-helical proteins, in which the membrane-spanning regions are made up of α-helices. Given the obvious biological and medical significance of these proteins, it is of tremendous practical importance to identify the location of transmembrane segments. The difficulty of inferring the secondary or tertiary structure of transmembrane proteins using experimental techniques has led to a surge of interest in applying techniques from machine learning and bioinformatics to infer secondary structure from primary structure in these proteins. We are therefore interested in determining which physicochemical properties are most useful for discriminating transmembrane …

Iloop - A Web Application For Two-Channel Microarray Interwoven Loop Design, Mehdi Pirooznia, Ping Gong, Jack Y. Yang, Mary Qu Yang, Edward J. Perkins, Youping Deng

Faculty Publications

Microarray technology is widely applied to address complex scientific questions. However, there remain fundamental issues on how to design experiments to ensure that the resulting data enables robust statistical analysis. Interwoven loop design has several advantages over other designs. However it suffers in the complexity of design. We have implemented an online web application which allows users to find optimal loop designs for two-color microarray experiments. Given a number of conditions (such as treatments or time points) and replicates, the application will find the best possible design of the experiment and output experimental parameters. It is freely available from http://mcbc.usm.edu/iloop …

Batch Blast Extractor: An Automated Blastx Parser Application, Mehdi Pirooznia, Edward J. Perkins, Youping Deng

Faculty Publications

Motivation

BLAST programs are very efficient in finding similarities for sequences. However for large datasets such as ESTs, manual extraction of the information from the batch BLAST output is needed. This can be time consuming, insufficient, and inaccurate. Therefore implementation of a parser application would be extremely useful in extracting information from BLAST outputs.

Results

We have developed a java application, Batch Blast Extractor, with a user friendly graphical interface to extract information from BLAST output. The application generates a tab delimited text file that can be easily imported into any statistical package such as Excel or SPSS for further …

A Comparative Study Of Different Machine Learning Methods On Microarray Gene Expression Data, Mehdi Pirooznia, Jack Y. Yang, Mary Qu Yang, Youping Deng

Faculty Publications

Background

Several classification and feature selection methods have been studied for the identification of differentially expressed genes in microarray data. Classification methods such as SVM, RBF Neural Nets, MLP Neural Nets, Bayesian, Decision Tree and Random Forrest methods have been used in recent studies. The accuracy of these methods has been calculated with validation methods such as v-fold validation. However there is lack of comparison between these methods to find a better framework for classification, clustering and analysis of microarray gene expression results.

Results

In this study, we compared the efficiency of the classification methods including; SVM, RBF Neural Nets, …

Transcriptome Profiling Of Saccharomyces Cerevisiae Mutants Lacking C2h2 Zinc Finger Proteins, Jinghe Mao, Tanwir Habib, Ming Shenwu, Baobin Kang, Wilbur Allen, Lashonda Robertson, Jack Y. Yang, Youping Deng

Faculty Publications

Background

The budding yeast Saccharomyces cerevisiae is a eukaryotic organism with extensive genetic redundancy. Large-scale gene deletion analysis has shown that over 80% of the ~6200 predicted genes are nonessential and that the functions of 30% of all ORFs remain unclassified, implying that yeast cells can tolerate deletion of a substantial number of individual genes. For example, a class of zinc finger proteins containing C2H2 zinc fingers in tandem arrays of two or three is predicted to be transcription factors; however, seven of the thirty-one predicted genes of this class are nonessential, and their functions are poorly understood. In this …

Assessment Of Key Parameters To Achieve Bacteria Transformability In E. Coli And A. Tumefaciens, Zach Regelin

Honors Program Theses

ln this project, growth and transformability of E. coli and A. tumefaciens were investigated. The growth of the bacterial species was monitored under different key parameters including: the strain of the bacteria, the inoculum source (a fresh plate or frozen glycerol stock), and the media type. Growth was monitored by measuring the optical density (OD). Using E. coli strains Dh5a and CdB\ it was determined that the strain, the media type, and the amount of inoculum had a great effect on the growth but the source of the inoculum had little effect. For A. tumefaciens, the strain and the media …

Whole Genome Duplications And Contracted Breakpoint Graphs, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

The genome halving problem, motivated by the whole genome duplication events in molecular evolution, was solved by El-Mabrouk and Sankoff in the pioneering paper [SIAM J. Comput., 32 (2003), pp. 754–792]. The El-Mabrouk–Sankoff algorithm is rather complex, inspiring a quest for a simpler solution. An alternative approach to the genome halving problem based on the notion of the contracted breakpoint graph was recently proposed in [M. A. Alekseyev and P. A. Pevzner, IEEE/ACM Trans. Comput. Biol. Bioinformatics, 4 (2007), pp. 98–107]. This new technique reveals that while the El-Mabrouk–Sankoff result is correct in most cases, it does not hold in …

Colored De Bruijn Graphs And The Genome Halving Problem, Max A. Alekseyev, Pavel A. Pevzner

Faculty Publications

Breakpoint graph analysis is a key algorithmic technique in studies of genome rearrangements. However, breakpoint graphs are defined only for genomes without duplicated genes, thus limiting their applications in rearrangement analysis. We discuss a connection between the breakpoint graphs and de Bruijn graphs that leads to a generalization of the notion of breakpoint graph for genomes with duplicated genes. We further use the generalized breakpoint graphs to study the Genome Halving Problem (first introduced and solved by Nadia El-Mabrouk and David Sankoff). The El-Mabrouk-Sankoff algorithm is rather complex, and, in this paper, we present an alternative approach that is based …

Transcriptomic Analysis Of Rdx And Tnt Interactive Sublethal Effects In The Earthworm Eisenia Fetida, Ping Gong, Xin Guan, Laura S. Anouye, Youping Deng, Mehdi Pirooznia, Edward J. Perkins

Faculty Publications

Background

Explosive compounds such as TNT and RDX are recalcitrant contaminants often found co-existing in the environment. In order to understand the joint effects of TNT and RDX on earthworms, an important ecological and bioindicator species at the molecular level, we sampled worms (Eisenia fetida) exposed singly or jointly to TNT (50 mg/kg soil) and RDX (30 mg/kg soil) for 28 days and profiled gene expression in an interwoven loop designed microarray experiment using a 4k-cDNA array. Lethality, growth and reproductive endpoints were measured.

Results

Sublethal doses of TNT and RDX had no significant effects on the survival …

Polymorphisms Of Cul5 Are Associated With Cd4+ T Cell Loss In Hiv-1 Infected Individuals, Ping An, Priya Duggal, Li Hua Wang, Stephen J. O'Brien, Sharyne Donfield, James J. Goedert, John Phair, Susan Buchbinder, Gregory D. Kirk, Cheryl Winkler

Biology Faculty Articles

Human apolipoprotein B mRNA editing enzyme, catalytic polypeptide-like 3 (Apobec3) antiretroviral factors cause hypermutation of proviral DNA leading to degradation or replication-incompetent HIV-1. However, HIV-1 viral infectivity factor (Vif) suppresses Apobec3 activity through the Cullin 5-Elongin B-Elongin C E3 ubiquitin ligase complex. We examined the effect of genetic polymorphisms in the CUL5 gene (encoding Cullin 5 protein) on AIDS disease progression in five HIV-1 longitudinal cohorts. A total of 12 single nucleotide polymorphisms (SNPs) spanning 93 kb in the CUL5 locus were genotyped and their haplotypes inferred. A phylogenetic network analysis revealed that CUL5 haplotypes were grouped into two clusters …

Potential For Stimulating Host Anti-Tumor Immune Response Via Rnai-Mediated Local Foxp3 Knockdown, N. Klaiber

Chemistry & Biochemistry Faculty Publications

Neoplastic growths represent a unique challenge for the host immune system. As they are indeed derived from self, many of the same mechanisms operating to prevent autoimmunity also provide an umbrella beneath which malignant cells are free to proliferate.1 Central among these immune regulatory boundaries are an influential subset of lymphocytes known as T regs. Hypothesized to exist decades ago, yet eluding definitive characterization until relatively recently, T regs have been demonstrated to play a crucial role in the proper functioning of the immune system as a whole. They may also, however, represent one of the primary obstacles to successful …

Sequence And The Developmental And Tissue-Specific Regulation Of The First Complete Vitellogenin Message From Ticks, Deborah M. Thompson, Sayed M.S. Khalil, Laura A. Jeffers, Daniel E. Sonenshine, Robert D. Mitchell, Christopher J. Osgood, R. Michael Roe

Biological Sciences Faculty Publications

The first full-length mRNA for vitellogenin (Vg) from ticks was sequenced. This also represents the first complete sequence of Vg from the Chelicerata and of a heme binding Vg. The Vg cDNA from the American dog tick, Dermacentor variabilis was 5744nt in length (GenBank Accession number AY885250), which coded for a protein of 1843aa with a calculated molecular weight of 208kD. This protein had an 18 aa signal sequence, a single RXXR cleavage signal that would generate two subunits (49.5 and 157K in molecular weight) and lipoprotein N-terminal and carboxy von Willebrand factor type D domains. Tryptic digest MS analysis …

Tissue And Life Stage Distribution Of A Defensin-Like Gene In The Lone Star Tick Amblyomma Americanum, S. Michelle Todd, Daniel E. Sonenshine, Wayne L. Hynes

Biological Sciences Faculty Publications

The transcript sequence of the Amblyomma americanum Linnaeus (Acari: Ixodidae) defensin, termed amercin (amn), was ascertained and a 219-bp amn coding region identified. The gene encodes a 72-amino acid prepropeptide with a putative 37-amino acid mature peptide. This gene shows little similarity to either of the defensins from Amblyomma hebraeum Koch, the only other Amblyomma species for which a defensin has been described. Sequence comparisons with other tick defensins reveal amn to be shorter (6 bp or 2 amino acids) than the Ixodes scapularis Linnaeus (Acari: Ixodidae) and Dermacentor variabilis (Say) (Acari: Ixodidae) defensin sequences. The amercin prepropeptide …

Sensory Genes And Mate Choice: Evidence That Duplications, Mutations, And Adaptive Evolution Alter Variation In Mating Cue Genes And Their Receptors, Lisa Horth

Biological Sciences Faculty Publications

Fascinating new data, revealed through gene sequencing, comparative genomics, and genetic engineering, precisely establish which genes are involved in mate choice and mating activity—behaviors that are surprisingly understudied from a genetic perspective. Discussed here are some of the recently identified visual and chemosensory genes that are involved in mate choice and mating behavior. These genes’ products are involved in the production, transmission, and receipt of crucial sensory mate-choice cues that affect fitness. This review exposes newfound evidence that alternative splicing, gene-expression pattern changes, and molecular genetic variation in sensory genes are crucial for both intra- and interspecific mate choice and …

Flavin Charge Transfer Transitions Assist Dna Photolyase Electron Transfer, Spiros S. Skourtis, Tatiana Prytkova, David Beratan

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

This contribution describes molecular dynamics, semi-empirical and ab-initio studies of the primary photo-induced electron transfer reaction in DNA photolyase. DNA photolyases are FADH−-containing proteins that repair UV-damaged DNA by photo-induced electron transfer. A DNA photolyase recognizes and binds to cyclobutatne pyrimidine dimer lesions of DNA. The protein repairs a bound lesion by transferring an electron to the lesion from FADH−, upon photo-excitation of FADH− with 350–450 nm light. We compute the lowest singlet excited states of FADH− in DNA photolyase using INDO/S configuration interaction, time-dependent density-functional, and time-dependent Hartree-Fock methods. The calculations identify the lowest singlet excited state of FADH− …

Functional Interplay Between The B-Box 2 And The B30.2(Spry) Domains Of Trim5Α, Xi Ling, Byeongwoon Song, Shi-Hua Xiang, Joseph Sodroski

Nebraska Center for Virology: Faculty Publications

The retroviral restriction factors, TRIM5α and TRIMCyp, consist of RING and B-box 2 domains separated by a coiled coil from carboxy-terminal domains. These carboxy-terminal domains (the B30.2(SPRY) domain in TRIM5α and the cyclophilin A domain in TRIMCyp) recognize the retroviral capsid. Here we show that some B-box 2 changes in TRIM5α, but not in TRIMCyp, resulted in decreased human immunodeficiency virus (HIV-1) capsid binding. The phenotypic effects of these B-box 2 changes on the restriction of retroviral infection depended on the potency of restriction and the affinity of the TRIM5α interaction with the viral capsid, two properties specified by the …

Characterization Of Human Immunodeficiency Virus Type 1 Monomeric And Trimeric Gp120 Glycoproteins Stabilized In The Cd4-Bound State: Antigenicity, Biophysics, And Immunogenicity, Barna Dey, Marie Pancera, Krisha Svehla, Yuuei Shu, Shi-Hua Xiang, Jeffrey Vainshtein, Yuxing Li, Joseph Sodroski, Peter D. Kwong, John R. Mascola, Richard Wyatt

Nebraska Center for Virology: Faculty Publications

The human immunodeficiency virus type 1 exterior gp120 envelope glycoprotein is highly flexible, and this flexibility may contribute to the inability of monomeric gp120 immunogens to elicit broadly neutralizing antibodies. We previously showed that an S375W modification of a critical interfacial cavity central to the primary receptor binding site, the Phe43 cavity, stabilizes gp120 into the CD4-bound state. However, the immunological effects of this cavity-altering replacement were never tested. Subsequently, we screened other mutations that, along with the S375W alteration, might further stabilize the CD4-bound state. Here, we define a selected second cavity-altering replacement, T257S, and analyze the double mutations …

Georgeoral Immunization Of Rhesus Macaques With Adenoviral Hiv Vaccines Using Enteric-Coated Capsules, George T. Mercier, Pramod N. Nehete, Marco F. Passeri, Bharti N. Nehete, Eric A. Weaver, Nancy Smyth Templeton, Kimberly Schluns, Stephanie S. Buchl, K. Jagannadha Sastry, Michael A. Barry

Nebraska Center for Virology: Faculty Publications

Targeted delivery of vaccine candidates to the gastrointestinal (GI) tract holds potential for mucosal immunization, particularly against mucosal pathogens like the human immunodeficiency virus (HIV). Among the different strategies for achieving targeted release in the GI tract, namely the small intestine, pH sensitive enteric coating polymers have been shown to protect solid oral dosage forms from the harsh digestive environment of the stomach and dissolve relatively rapidly in the small intestine by taking advantage of the luminal pH gradient. We developed an enteric polymethacrylate formulation for coating hydroxy-propyl-methyl-cellulose (HPMC) capsules containing lyophilized Adenoviral type 5 (Ad5) vectors expressing HIV-1 gag …

The Arabidopsis Homologs Of Trithorax (Atx1) And Enhancer Of Zeste (Clf) Establish ‘Bivalent Chromatin Marks’ At The Silent Agamous Locus, Abdelaty Saleh, Ayed Al-Abdallat, Ivan Ndamukong, Raul Alvarez-Venegas, Zoya Avramova

School of Biological Sciences: Faculty Publications

Tightly balanced antagonism between the Polycomb group (PcG) and the Trithorax group (TrxG) complexes maintain Hox expression patterns in Drosophila and murine model systems. Factors belonging to the PcG/TrxG complexes control various processes in plants as well but whether they participate in mechanisms that antagonize, balance or maintain each other’s effects at a particular gene locus is unknown. CURLY LEAF (CLF), an Arabidopsis homolog of enhancer of zeste (EZ) and the ARABIDOPSIS HOMOLOG OF TRITHORAX (ATX1) control the expression of the flower homeotic gene AGAMOUS (AG). Disrupted ATX1 or CLF function results in misexpression of AG, recognizable …

Asymmetric Localizations Of Lin-17/Fz And Mig-5/Dsh Are Involved In The Asymmetric B Cell Division In C. Elegans, Mingfu Wu, Michael A. Herman

School of Biological Sciences: Faculty Publications

LIN-44/Wnt and LIN-17/Frizzled (Fz) function in a planar cell polarity (PCP)-like pathway to regulate the asymmetric B cell division in Caenorhabditis elegans. We observed asymmetric localization of LIN-17/Frizzled (Fz) and MIG-5/Disheveled (Dsh) during the B cell division. LIN-17∷GFP was asymmetrically localized within the B cell prior to and after the B cell division and correlated with B cell polarity. Asymmetric localization of LIN-17∷GFP was dependent upon LIN-44/Wnt and MIG-5/Dsh function. The LIN-17 transmembrane domain and a portion of the cysteine-rich domain (CRD) were required for LIN-17 function and asymmetric distribution to the B cell daughters, while the conserved KTXXXW …

Microarray Challenges In Ecology, Jan E. Kammenga, Michael A. Herman, N. Joop Ouborg, Loretta Johnson, Rainer Bretling

School of Biological Sciences: Faculty Publications

Microarrays are used to measure simultaneously the amount of mRNAs transcribed from many genes. They were originally designed for gene expression profiling in relatively simple biological systems, such as cell lines and model systems under constant laboratory conditions. This poses a challenge to ecologists who increasingly want to use microarrays to unravel the genetic mechanisms underlying complex interactions among organisms and between organisms and their environment. Here, we discuss typical experimental and statistical problems that arise when analyzing genome-wide expression profiles in an ecological context. We show that experimental design and environmental confounders greatly influence the identification of candidate genes …

Alternative Exon Usage Selectively Determines Both Tissue Distribution And Subcellular Localization Of The Acyl-Coa Thioesterase 7 Gene Products., Mary Hunt, Sinead Greene, Kjell Hultenby, L. Thomas Svensson, Susanna Engberg, Stefan E H Alexson

Articles

Acyl-CoA thioesterases (ACOTs) catalyze the hydrolysis of acyl-CoAs to free fatty acids and coenzyme A. Recent studies have demonstrated that one gene named Acot7, reported to be mainly expressed in brain and testis, is transcribed in several different isoforms by alternative usage of first exons. Strongly decreased levels of ACOT7 activity and protein in both mitochondria and cytosol was reported in patients diagnosed with fatty acid oxidation defects, linking ACOT7 function to regulation of fatty acid oxidation in other tissues. In this study, we have identified five possible first exons in mouse Acot7 (Acot7a-e) and show that all five first …

Chlamydia Trachomatis Detection In Cervical Preservcyt Specimens From An Irish Urban Female Population, Helen Keegan, Fergus Ryan, Alison Malkin, M. Griffin, Helen Lambkin

Articles

Objective: The aim of this study was to determine the prevalence of cervical Chlamydia trachomatis infection by polymerase chain reaction (PCR) in urban women undergoing routine cervical cytological screening and to investigate the relationship with age, cytology, smoking status and concurrent human papillomavirus (HPV) infection. Methods: A total of 996 women (age range 16–69 years) attending general practitioners for routine liquid-based cervical smear screening in the Dublin area were recruited in the study of prevalence of C. trachomatis. Informed consent was obtained and liquid-based cytology (LBC) specimens were sent for cytological screening. DNA was extracted from residual LBC and tested …