Medical Genetics Commons^™

Codont5: A Multi-Task Codon Language Model For Species-To-Species Translation, Ashley N. Babjac

Doctoral Dissertations

DNA (DeoxyriboNucleic Acid) carries the genetic information for the biological processes and function of all organisms. It is composed of nucleotides, which can be grouped into 3-mer triplets called codons. It is well known that codons encoding the same amino acid, referred to as "synonymous" codons, are selected with differing frequencies between organisms. Prior research has revealed there are codons used with much higher frequency than others, causing to them being "preferred" in highly expressed genes. This has led to the development of multiple computational models that do a good job predicting gene expression in some protein-coding genes; however, their …

The Ratio Method: Addressing Complex Tort Liability In The Fourth Industrial Revolution, Harrison C. Margolin, Grant H. Frazier

St. Mary's Law Journal

Emerging technologies of the Fourth Industrial Revolution show fundamental promise for improving productivity and quality of life, though their misuse may also cause significant social disruption. For example, while artificial intelligence will be used to accelerate society’s processes, it may also displace millions of workers and arm cybercriminals with increasingly powerful hacking capabilities. Similarly, human gene editing shows promise for curing numerous diseases, but also raises significant concerns about adverse health consequences related to the corruption of human and pathogenic genomes.

In most instances, only specialists understand the growing intricacies of these novel technologies. As the complexity and speed of …

User-Centered Design Of Multi-Gene Sequencing Panel Reports For Clinicians., Elizabeth Cutting, Meghan Banchero, Amber L. Beitelshees, James J. Cimino, Guilherme Del Fiol, Ayse P. Gurses, Mark A. Hoffman, Linda Jo Bone Jeng, Kensaku Kawamoto, Mark Kelemen, Harold Alan Pincus, Alan R. Shuldiner, Marc S. Williams, Toni I. Pollin, Casey Lynnette Overby

Manuscripts, Articles, Book Chapters and Other Papers

The objective of this study was to develop a high-fidelity prototype for delivering multi-gene sequencing panel (GS) reports to clinicians that simulates the user experience of a final application. The delivery and use of GS reports can occur within complex and high-paced healthcare environments. We employ a user-centered software design approach in a focus group setting in order to facilitate gathering rich contextual information from a diverse group of stakeholders potentially impacted by the delivery of GS reports relevant to two precision medicine programs at the University of Maryland Medical Center. Responses from focus group sessions were transcribed, coded and …

Data Mining The Functional Characterizations Of Proteins To Predict Their Cancer-Relatedness, Peter Revesz, Christopher Assi

School of Computing: Faculty Publications

This paper considers two types of protein data. First, data about protein function described in a number of ways, such as, GO terms and PFAM families. Second, data about whether individual proteins are experimentally associated with cancer by an anomalous elevation or lowering of their expressions within cancerous cells. We combine these two types of protein data and test whether the first type of data, that is, the functional descriptors, can predict the second type of data, that is, cancer-relatedness. By using data mining and machine learning, we derive a classifier algorithm that using only GO term and PFAM family …

Piscine Myocarditis Virus (Pmcv) In Wild Atlantic Salmon Salmo Salar, Torstein Tengs Dr.

Dr. Torstein Tengs

Cardiomyopathy syndrome (CMS) is a severe cardiac disease of sea-farmed Atlantic salmon Salmo salar L., but CMS-like lesions have also been found in wild Atlantic salmon. In 2010 a double-stranded RNA virus of the Totiviridae family, provisionally named piscine myocarditis virus (PMCV), was described as the causative agent of CMS. In the present paper we report the first detection of PMCV in wild Atlantic salmon. The study is based on screening of 797 wild Atlantic salmon by real-time RT-PCR. The samples were collected from 35 different rivers along the coast of Norway, and all individuals included in the study were …

Prevalence Of Tick Borne Encephalitis Virus In Tick Nymphs In Relation To Climatic Factors On The Southern Coast Of Norway, Torstein Tengs Dr.

Dr. Torstein Tengs

BACKGROUND

Tick-borne encephalitis (TBE) is among the most important vector borne diseases of humans in Europe and is currently identified as a major health problem in many countries. TBE endemic zones have expanded over the past two decades, as well as the number of reported cases within endemic areas. Multiple factors are ascribed for the increased incidence of TBE, including climatic change. The number of TBE cases has also increased in Norway over the past decade, and the human cases cluster along the southern coast of Norway. In Norway the distribution and prevalence of TBE virus (TBEV) in tick populations …

A Strain Of Piscine Myocarditis Virus (Pmcv) Infecting Argentina Silus (Ascanius), Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.

Quantification Of Piscine Reovirus (Prv) At Different Stages Of Atlantic Salmon Salmo Salar Production, Torstein Tengs Dr.

Dr. Torstein Tengs

The newly described piscine reovirus (PRV) appears to be associated with the development of heart and skeletal muscle inflammation (HSMI) in farmed Atlantic salmon Salmo salar L. PRV seems to be ubiquitous among fish in Norwegian salmon farms, but high viral loads and tissue distribution support a causal relationship between virus and disease. In order to improve understanding of the distribution of PRV in the salmon production line, we quantified PRV by using real-time PCR on heart samples collected at different points in the life cycle from pre-smolts to fish ready for slaughter. PRV positive pre-smolts were found in about …

Genetic Studies Of Complex Human Diseases: Characterizing Snp-Disease Associations Using Bayesian Networks, Bing Han, Xue-Wen Chen, Zohreh Talebizadeh, Hua Xu

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Detecting epistatic interactions plays a significant role in improving pathogenesis, prevention, diagnosis, and treatment of complex human diseases. Applying machine learning or statistical methods to epistatic interaction detection will encounter some common problems, e.g., very limited number of samples, an extremely high search space, a large number of false positives, and ways to measure the association between disease markers and the phenotype.

Results

To address the problems of computational methods in epistatic interaction detection, we propose a score-based Bayesian network structure learning method, EpiBN, to detect epistatic interactions. We apply the proposed method to both simulated datasets and …

Down-Weighting Overlapping Genes Improves Gene Set Analysis, Adi Tarca, Sorin Draghici, Gaurav Bhatti, Roberto Romero

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

The identification of gene sets that are significantly impacted in a given condition based on microarray data is a crucial step in current life science research. Most gene set analysis methods treat genes equally, regardless how specific they are to a given gene set.

Results

In this work we propose a new gene set analysis method that computes a gene set score as the mean of absolute values of weighted moderated gene t-scores. The gene weights are designed to emphasize the genes appearing in few gene sets, versus genes that appear in many gene sets. We demonstrate the …

Bio::Phylo-Phyloinformatic Analysis Using Perl, Rutger A. Vos, Jason Caravas, Klaas Hartmann, Mark A. Jensen, Chase Miller

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Phyloinformatic analyses involve large amounts of data and metadata of complex structure. Collecting, processing, analyzing, visualizing and summarizing these data and metadata should be done in steps that can be automated and reproduced. This requires flexible, modular toolkits that can represent, manipulate and persist phylogenetic data and metadata as objects with programmable interfaces.

Results

This paper presents Bio::Phylo, a Perl5 toolkit for phyloinformatic analysis. It implements classes and methods that are compatible with the well-known BioPerl toolkit, but is independent from it (making it easy to install) and features a richer API and a data model that is …

Prevalence Of Piscine Myocarditis Virus (Pmcv) In Marine Fish Species, Torstein Tengs Dr.

Dr. Torstein Tengs

No abstract.

A Novel Totivirus And Piscine Reovirus (Prv) In Atlantic Salmon (Salmo Salar) With Cardiomyopathy Syndrome (Cms), Torstein Tengs

Dr. Torstein Tengs

BACKGROUNDCardiomyopathy syndrome (CMS) is a severe disease affecting large farmed Atlantic salmon. Mortality often appears without prior clinical signs, typically shortly prior to slaughter. We recently reported the finding and the complete genomic sequence of a novel piscine reovirus (PRV), which is associated with another cardiac disease in Atlantic salmon; heart and skeletal muscle inflammation (HSMI). In the present work we have studied whether PRV or other infectious agents may be involved in the etiology of CMS.RESULTSUsing high throughput sequencing on heart samples from natural outbreaks of CMS and from fish experimentally challenged with material from fish diagnosed with CMS …

Heart And Skeletal Muscle Inflammation Of Farmed Salmon Is Associated With Infection With A Novel Reovirus, Torstein Tengs

Dr. Torstein Tengs

Atlantic salmon (Salmo salar L.) mariculture has been associated with epidemics of infectious diseases that threaten not only local production, but also wild fish coming into close proximity to marine pens and fish escaping from them. Heart and skeletal muscle inflammation (HSMI) is a frequently fatal disease of farmed Atlantic salmon. First recognized in one farm in Norway in 1999, HSMI was subsequently implicated in outbreaks in other farms in Norway and the United Kingdom. Although pathology and disease transmission studies indicated an infectious basis, efforts to identify an agent were unsuccessful. Here we provide evidence that HSMI is associated …

Non-Prejudiced Detection And Characterization Of Genetic Modifications, Torstein Tengs

Dr. Torstein Tengs

The application of gene technology is becoming widespread much thanks to the rapid increase in technology, resource, and knowledge availability. Consequently, the diversity and number of genetically modified organisms (GMOs) that may find their way into the food chain or the environment, intended or unintended, is rapidly growing. From a safety point of view the ability to detect and characterize in detail any GMO, independent of publicly available information, is fundamental. Pre-release risk assessments of GMOs are required in most jurisdictions and are usually based on application of technologies with limited ability to detect unexpected rearrangements and insertions. We present …

Comparison Of Nine Different Real-Time Pcr Chemistries For Qualitative And Quantitative Applications In Gmo Detection, Torstein Tengs

Dr. Torstein Tengs

Several techniques have been developed for detection and quantification of genetically modified organisms, but quantitative real-time PCR is by far the most popular approach. Among the most commonly used realtime PCR chemistries are TaqMan probes and SYBR green, but many other detection chemistries have also been developed. Because their performance has never been compared systematically, here we present an extensive evaluation of some promising chemistries: sequenceunspecific DNA labeling dyes (SYBR green), primer-based technologies (AmpliFluor, Plexor, Lux primers), and techniques involving double-labeled probes, comprising hybridization (molecular beacon) and hydrolysis (TaqMan, CPT, LNA, and MGB) probes, based on recently published experimental data. …

Uniqueprimer - A Web Utility For Design Of Specific Pcr Primers And Probes, Torstein Tengs

Dr. Torstein Tengs

We have developed a web-based tool for design of specific PCR primers and probes. The program allows you to enter primer sequence information as well as an optional probe, and sequence similarity searches (MegaBLAST) will be performed to see if the sequences match the same sequence entry in the specified database. If primers (and probe) match, this will be reported. The program can handle overlapping amplicons, amplification from a single primer, ambiguous bases and other problematic cases.

A Quantitative Taqman Mgb Real-Time Polymerase Chain Reaction Based Assay For Detection Of The Causative Agent Of Crayfish Plague Aphanomyces Astaci, Torstein Tengs

Dr. Torstein Tengs

Here we present the development and first validation of a TaqMan minor groove binder (MGB) real-time polymerase chain reaction (RT-PCR) method for quantitative and highly specific detection of Aphanomyces astaci, the causative agent of crayfish plague. The assay specificity was experimentally assessed by testing against DNA representative of closely related oomycetes, and theoretically assessed by additional sequence similarity analyses comparing the primers and probe sequences to available sequences in EMBL/GenBank. The target of the assay is a 59 bp unique sequence motif of A. astaci found in the internal transcribed spacer 1 of the nuclear ribosomal gene cluster. A standard …

Characterization Of Unknown Genetic Modifications Using High Throughput Sequencing And Computational Subtraction, Torstein Tengs

Dr. Torstein Tengs

Background

When generating a genetically modified organism (GMO), the primary goal is to give a target organism one or several novel traits by using biotechnology techniques. A GMO will differ from its parental strain in that its pool of transcripts will be altered. Currently, there are no methods that are reliably able to determine if an organism has been genetically altered if the nature of the modification is unknown.

Results

We show that the concept of computational subtraction can be used to identify transgenic cDNA sequences from genetically modified plants. Our datasets include 454-type sequences from a transgenic line of …

Droid: The Drosophila Interactions Database, A Comprehensive Resource For Annotated Gene And Protein Interactions, Jingkai Yu, Svetlana Pacifico, Guozhen Liu, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Charting the interactions among genes and among their protein products is essential for understanding biological systems. A flood of interaction data is emerging from high throughput technologies, computational approaches, and literature mining methods. Quick and efficient access to this data has become a critical issue for biologists. Several excellent multi-organism databases for gene and protein interactions are available, yet most of these have understandable difficulty maintaining comprehensive information for any one organism. No single database, for example, includes all available interactions, integrated gene expression data, and comprehensive and searchable gene information for the important model organism, Drosophila melanogaster. …

Statistical Issues In Proteomic Research, Jeffrey S. Morris

Jeffrey S. Morris

No abstract provided.

A Database And Tool, Im Browser, For Exploring And Integrating Emerging Gene And Protein Interaction Data For Drosophila, Svetlana Pacifico, Guozhen Liu, Stephen Guest, Jodi R. Parrish, Farshad Fotouhi, Russell L. Finley Jr

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Biological processes are mediated by networks of interacting genes and proteins. Efforts to map and understand these networks are resulting in the proliferation of interaction data derived from both experimental and computational techniques for a number of organisms. The volume of this data combined with the variety of specific forms it can take has created a need for comprehensive databases that include all of the available data sets, and for exploration tools to facilitate data integration and analysis. One powerful paradigm for the navigation and analysis of interaction data is an interaction graph or map that represents proteins …

K-Spmm: A Database Of Murine Spermatogenic Promoters Modules & Motifs, Yi Lu, Adrian E. Platts, G Charles Ostermeier, Stephen A. Krawetz

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

Understanding the regulatory processes that coordinate the cascade of gene expression leading to male gamete development has proven challenging. Research has been hindered in part by an incomplete picture of the regulatory elements that are both characteristic of and distinctive to the broad population of spermatogenically expressed genes.

Description

K-SPMM, a database of murine Spermatogenic Promoters Modules and Motifs, has been developed as a web-based resource for the comparative analysis of promoter regions and their constituent elements in developing male germ cells. The system contains data on 7,551 genes and 11,715 putative promoter regions …

Incremental Genetic K-Means Algorithm And Its Application In Gene Expression Data Analysis, Yi Lu, Shiyong Lu, Farshad Fotouhi, Youping Deng, Susan J. Brown

Wayne State University Associated BioMed Central Scholarship

Abstract

Background

In recent years, clustering algorithms have been effectively applied in molecular biology for gene expression data analysis. With the help of clustering algorithms such as K-means, hierarchical clustering, SOM, etc, genes are partitioned into groups based on the similarity between their expression profiles. In this way, functionally related genes are identified. As the amount of laboratory data in molecular biology grows exponentially each year due to advanced technologies such as Microarray, new efficient and effective methods for clustering must be developed to process this growing amount of biological data.

Results

In this paper, we propose a new clustering …