Genomics Commons^™

Epistasis In Predator-Prey Relationships, Iuliia Inozemtseva

College of Graduate Studies: Theses & Dissertations

Epistasis is the interaction between two or more genes to control a single phenotype. We model epistasis of the prey in a two-locus two-allele problem in a basic predator- prey relationship. The resulting model allows us to examine both population sizes as well as genotypic and phenotypic frequencies. In the context of several numerical examples, we show that if epistasis results in an undesirable or desirable phenotype in the prey by making the particular genotype more or less susceptible to the predator or dangerous to the predator, elimination of undesirable phenotypes and then genotypes occurs.

Crispr-Cas Gene Engineering And The Characterization Of Cis-Regulatory Elements (Cres) In The Non-Coding Genome, Garrett Wilson

Summer Community of Scholars Posters (RCEU and HCR Combined Programs)

No abstract provided.

Egonet: Identification Of Human Disease Ego-Network Modules, Rendong Yang, Yun Bai, Zhaohui Qin, Tianwei Yu

PCOM Scholarly Works

Background: Mining novel biomarkers from gene expression profiles for accurate disease classification is challenging due to small sample size and high noise in gene expression measurements. Several studies have proposed integrated analyses of microarray data and protein-protein interaction (PPI) networks to find diagnostic subnetwork markers. However, the neighborhood relationship among network member genes has not been fully considered by those methods, leaving many potential gene markers unidentified. The main idea of this study is to take full advantage of the biological observation that genes associated with the same or similar diseases commonly reside in the same neighborhood of molecular networks.Results: …

Small Rna Expression During Programmed Rearragement Of A Vertebrate Genome, Joseph R. Herdy Iii

Theses and Dissertations--Biology

The sea lamprey (Petromyzon marinus) undergoes programmed genome rearrangements (PGRs) during embryogenesis that results in the deletion of ~0.5 Gb of germline DNA from the somatic lineage. The underlying mechanism of these rearrangements remains largely unknown. miRNAs (microRNAs) and piRNAs (PIWI interacting RNAs) are two classes of small noncoding RNAs that play important roles in early vertebrate development, including differentiation of cell lineages, modulation of signaling pathways, and clearing of maternal transcripts. Here, I utilized next generation sequencing to determine the temporal expression of miRNAs, piRNAs, and other small noncoding RNAs during the first five days of lamprey …

Methods For Integrative Analysis Of Genomic Data, Paul Manser

Theses and Dissertations

In recent years, the development of new genomic technologies has allowed for the investigation of many regulatory epigenetic marks besides expression levels, on a genome-wide scale. As the price for these technologies continues to decrease, study sizes will not only increase, but several different assays are beginning to be used for the same samples. It is therefore desirable to develop statistical methods to integrate multiple data types that can handle the increased computational burden of incorporating large data sets. Furthermore, it is important to develop sound quality control and normalization methods as technical errors can compound when integrating multiple genomic …

A Systems Biology Approach To Detect Eqtls Associated With Mirna And Mrna Co-Expression Networks In The Nucleus Accumbens Of Chronic Alcoholic Patients, Mohammed Mamdani

Theses and Dissertations

Alcohol Dependence (AD) is a chronic substance use disorder with moderate heritability (60%). Linkage and genome-wide association studies (GWAS) have implicated a number of loci; however, the molecular mechanisms underlying AD are unclear. Advances in systems biology allow genome-wide expression data to be integrated with genetic data to detect expression quantitative trait loci (eQTL), polymorphisms that regulate gene expression levels, influence phenotypes and are significantly enriched among validated genetic signals for many commonly studied traits including AD.

We integrated genome-wide mRNA and miRNA expression data with genotypic data from the nucleus accumbens (NAc), a major addiction-related brain region, of 36 …

Genome-Wide Sequencing Of Small Rnas Reveals A Tissue-Specific Loss Of Conserved Microrna Families In Echinococcus Granulosus, Yun Bai, Zhuangzhi Zhang, Lei Jin, Hui Kang, Yongquiang Zhu, Lu Zhang, Xia Li, Fengshou Ma, Li Zhao, Et Al.

PCOM Scholarly Works

Background: MicroRNAs (miRNAs) are important post-transcriptional regulators which control growth and development in eukaryotes. The cestode Echinococcus granulosus has a complex life-cycle involving different development stages but the mechanisms underpinning this development, including the involvement of miRNAs, remain unknown. Results: Using Illumina next generation sequencing technology, we sequenced at the genome-wide level three small RNA populations from the adult, protoscolex and cyst membrane of E. granulosus. A total of 94 pre-miRNA candidates (coding 91 mature miRNAs and 39 miRNA stars) were in silico predicted. Through comparison of expression profiles, we found 42 mature miRNAs and 23 miRNA stars expressed with …

Introducing A Novel Method For Genetic Analysis Of Autism Spectrum Disorder, Sepideh Nouri

Dissertations and Theses (Open Access)

Autism is a spectrum of neurological disorders that is characterized by repetitive and stereotyped behaviors, lack of social skills in verbal and non-verbal communications, and intellectual disability. Recent statistics shows that 1 out of every 88 children in the US is affected by autism.

In this thesis, I first review previous studies on genetic association analyses of autism spectrum disorder. A large number of these studies fall into two categories: Genome Wide Association Studies (GWAS) and sequencing studies. Although GWAS are able to identify multiple common risk variants associated with different diseases, these common variants explain only a small portion …

Personal Genomics: Good, Evil, Or Both?, Emily Schmitt

CAHSS Intellectual Conversations

With the increasing availability of personal genomic testing, there have been warnings that the results may lead to discrimination by insurance companies, employers, or the community. In addition, some individuals fear potential identity theft and loss of personal autonomy, despite the benefits of discovering potential genetic risks and possibilities of more-focused treatments. This lecture will examine whether personal genomics is good, evil, or both.

Reflections On The Cost Of "Low-Cost" Whole Genome Sequencing: Framing The Health Policy Debate, Timothy Caulfield, Jim Evans, Amy Mcguire, Christopher Mccabe, Tania Bubela, Robert Cook-Deegan, Jennifer Fishman, Stuart Hogarth, Fiona A. Miller, Vardit Ravitsky, Barbara Biesecker, Pascal Borry, Mildred K. Cho, June C. Carroll, Holly Etchegary, Yann Joly, Kazuto Kato, Sandra Soo-Jim Lee, Karen H. Rothenberg, Pamela Sankar, Michael J. Szego, Pilar Ossorio, Daryl Pullman, Francois Rousseau, Wendy J. Ungar, Brenda Wilson

Faculty Scholarship

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.

Reflections On The Cost Of "Low-Cost" Whole Genome Sequencing: Framing The Health Policy Debate, Timothy Caulfield, Jim Evans, Amy Mcguire, Christopher Mccabe, Tania M. Bubela, Robert Cook-Deegan, Jennifer Fishman, Stuart Hogarth, Fiona A. Miller, Vardit Ravitsky

Office of the Provost

The cost of whole genome sequencing is dropping rapidly. There has been a great deal of enthusiasm about the potential for this technological advance to transform clinical care. Given the interest and significant investment in genomics, this seems an ideal time to consider what the evidence tells us about potential benefits and harms, particularly in the context of health care policy. The scale and pace of adoption of this powerful new technology should be driven by clinical need, clinical evidence, and a commitment to put patients at the centre of health care policy.

Homeotic Gene Teashirt (Tsh) Has A Neuroprotective Function In Amyloid-Beta 42 Mediated Neurodegeneration, Michael T. Moran, Meghana Tare, Madhuri Kango-Singh, Amit Singh

Biology Faculty Publications

Background: Alzheimer's disease (AD) is a debilitating age related progressive neurodegenerative disorder characterized by the loss of cognition, and eventual death of the affected individual. One of the major causes of AD is the accumulation of Amyloid-beta 42 (Aβ42) polypeptides formed by the improper cleavage of amyloid precursor protein (APP) in the brain. These plaques disrupt normal cellular processes through oxidative stress and aberrant signaling resulting in the loss of synaptic activity and death of the neurons. However, the detailed genetic mechanism(s) responsible for this neurodegeneration still remain elusive.

Methodology/Principal Findings: We have generated a transgenic Drosophila eye model where …

Detecting Modules In Multiplex Networks – An Application For Integrating Expression Profiles Across Multiple Species, Koon-Kiu Yan, Daifeng Wang, Joel Rozowsky, Henry Zheng, Baikang Pei, Mark Gerstein

Yale Day of Data

Multiplex network, a set of networks linked through interconnected layers, is a useful mathematical framework for data integration. Here, we present a general method to detect modules in multiplex networks and apply it in a specific biological context: to simultaneously cluster the genome-wide expression profiles of C. elegans and D. melanogaster generated by the ENOCDE and modENCODE consortia. The method revealed modules that are fundamentally cross-species and can either be conserved or species-specific. In general, the method could be applied in various contexts like the integration of different social networks.

Hypothesis Driven Single Nucleotide Polymorphism Search (Hydn-Snp-S), Rebecca J. Swett, Angela Elias, Jeffrey A. Miller, Gregory E. Dyson, G. AndréS Cisneros

Chemistry Faculty Research Publications

The advent of complete-genome genotyping across phenotype cohorts has provided a rich source of information for bioinformaticians. However the search for SNPs from this data is generally performed on a study-by-study case without any specific hypothesis of the location for SNPs that are predictive for the phenotype. We have designed a method whereby very large SNP lists (several gigabytes in size), combining several genotyping studies at once, can be sorted and traced back to their ultimate consequence in protein structure. Given a working hypothesis, researchers are able to easily search whole genome genotyping data for SNPs that link genetic locations …

Draft Genome Sequence Of A Mucoid Isolate Of Pseudomonas Aeruginosa Strain C7447m From A Patient With Cystic Fibrosis, Yeshi Yin, T. Ryan Withers, Shannon L. Johnson, Hongwei D. Yu

Biochemistry and Microbiology

Alginate overproduction by Pseudomonas aeruginosa, or mucoidy, plays an important role in the pathogenesis of chronic lung infections in cystic fibrosis (CF) patients. Here we report the draft genome sequence of a clinical isolate of mucoid P. aeruginosa strain C7447m from a CF patient with chronic lung infection.

Reactin: Regulatory Activity Inference Of Transcription Factors Underlying Human Diseases With Application To Breast Cancer, Mingzhu Zhu, Chun-Chi Liu, Chao Cheng

Dartmouth Scholarship

Genetic alterations of transcription factors (TFs) have been implicated in the tumorigenesis of cancers. In many cancers, alteration of TFs results in aberrant activity of them without changing their gene expression level. Gene expression data from microarray or RNA-seq experiments can capture the expression change of genes, however, it is still challenge to reveal the activity change of TFs. Here we propose a method, called REACTIN (REgulatory ACTivity INference), which integrates TF binding data with gene expression data to identify TFs with significantly differential activity between disease and normal samples. REACTIN successfully detect differential activity of estrogen receptor (ER) between …

Machine Learning And Genome Annotation: A Match Meant To Be?, Kevin Y. Yip, Chao Cheng, Mark Gerstein

Dartmouth Scholarship

By its very nature, genomics produces large, high-dimensional datasets that are well suited to analysis by machine learning approaches. Here, we explain some key aspects of machine learning that make it useful for genome annotation, with illustrative examples from ENCODE.

Can Long-Range Pcr Be Used To Amplify Genetically Divergent Mitochondrial Genomes For Comparative Phylogenetics? A Case Study Within Spiders (Arthropoda: Araneae), Andrew G. Briscoe, Sara Goodacre, Susan E. Masta, Martin I. Taylor, Miquel A. Arnedo, David Penny, John Kenny, Simon Creer

Biology Faculty Publications and Presentations

The development of second generation sequencing technology has resulted in the rapid production of large volumes of sequence data for relatively little cost, thereby substantially increasing the quantity of data available for phylogenetic studies. Despite these technological advances, assembling longer sequences, such as that of entire mitochondrial genomes, has not been straightforward. Existing studies have been limited to using only incomplete or nominally intra-specific datasets resulting in a bottleneck between mitogenome amplification and downstream high-throughput sequencing. Here we assess the effectiveness of a wide range of targeted long-range PCR strategies, encapsulating single and dual fragment primer design approaches to provide …

High Occurrence Of Functional New Chimeric Genes In Survey Of Rice Chromosome 3 Short Arm Genome Sequences, Chengjun Zhang, Jun Wang, Nicholas C. Marowsky, Manyuan Long, Rod A. Wing, Chuanzhu Fan

Biological Sciences Faculty Research Publications

In an effort to identify newly evolved genes in rice,we searched the genomes of Asian-cultivated rice Oryza sativa ssp. japonica and its wild progenitors, looking for lineage-specific genes. Using genome pairwise comparison of approximately 20-Mb DNA sequences from the chromosome 3 short arm (Chr3s) in six rice species, O. sativa, O. nivara, O. rufipogon, O. glaberrima, O. barthii, and O. punctata, combined with synonymous substitution rate tests and other evidence, we were able to identify potential recently duplicated genes, which evolved within the last 1 Myr. We identified 28 functional O. sativa genes, which …

Engaging Students In A Bioinformatics Activity To Introduce Gene Structure And Function, Barbara J. May

Biology Faculty Publications

Bioinformatics spans many fields of biological research and plays a vital role in mining and analyzing data. Therefore, there is an ever-increasing need for students to understand not only what can be learned from this data, but also how to use basic bioinformatics tools. This activity is designed to provide secondary and undergraduate biology students to a hands-on activity meant to explore and understand gene structure with the use of basic bioinformatic tools. Students are provided an “unknown” sequence from which they are asked to use a free online gene finder program to identify the gene. Students then predict the …