Computational Biology Commons^™

The Discovery Of A Novel Bacteria From A Large Co-Assembly Of Metagenomes, Matthew Finkelberg

Masters Theses

In the summer of 2022, a co-assembly of metagenome was created using the microbes found at Barres Woods in Harvard Forest. 14 samples were taken, and sample was split into the organic and mineral layer, which totals 28 Bulk MAGs. Within this Co-assembly, 4 different genomes were found which were designated with the phylum of FCPU426. Three of which were considered medium quality and one being assigned high quality. The novel phyla first appeared in NCBI and GTDB databases in June 2018. The name FCPU426 dates to 2010 and was named based on the 16s amplicon sequencing.

The novel phylum …

The Detection Of Putative Recessive Lethal Haplotypes In Irish Sheep Populations, Rory Mcauley

ORBioM (Open Research BioSciences Meeting)

In livestock populations, recessive lethal alleles are a known contributor to poor reproductive performance due to embryonic death in homozygous individuals. Despite their lethal effect in the recessive form, these alleles may be maintained at high frequencies among carrier animals because of their positive pleiotropic effects on economically important traits. Although several such recessive alleles have been identified in cattle and pig populations, limited studies have been completed in sheep, and none within Irish sheep populations. Genotype data for 69,034 animals from five major Irish sheep breeds genotyped on a variety of panels was available for this study. Only animals …

Tracing Evolution Of Gene Transfer Agents Using Comparative Genomics, Roman Kogay

Dartmouth College Ph.D Dissertations

The accumulating evidence suggest that viruses and their components can be domesticated by their hosts, equipping them with convenient molecular toolkits for various functions. One of such domesticated system is Gene Transfer Agents (GTAs) that are produced by some bacteria and archaea. GTAs morphologically resemble small phage-like particles and contain random fragments of their host genome. They are produced only by a small fraction of the microbial population and are released through a lysis of the host cell. Bioinformatic analyses suggest that GTAs are especially abundant in the taxonomic class of Alphaproteobacteria, where they are vertically inherited and evolve …

The Role Of Non-Coding Rnas In Myelodysplastic Neoplasms, Vasileios Georgoulis, Epameinondas Koumpis, Eleftheria Hatzimichael

Computational Medicine Center Faculty Papers

Myelodysplastic syndromes or neoplasms (MDS) are a heterogeneous group of myeloid clonal disorders characterized by peripheral blood cytopenias, blood and marrow cell dysplasia, and increased risk of evolution to acute myeloid leukemia (AML). Non-coding RNAs, especially microRNAs and long non-coding RNAs, serve as regulators of normal and malignant hematopoiesis and have been implicated in carcinogenesis. This review presents a comprehensive summary of the biology and role of non-coding RNAs, including the less studied circRNA, siRNA, piRNA, and snoRNA as potential prognostic and/or predictive biomarkers or therapeutic targets in MDS.

Modeling Nonsegmented Negative-Strand Rna Virus (Nnsv) Transcription With Ejective Polymerase Collisions And Biased Diffusion, Felipe-Andres Piedra

Research Symposium

Background: The textbook model of NNSV transcription predicts a gene expression gradient. However, multiple studies show non-gradient gene expression patterns or data inconsistent with a simple gradient. Regarding the latter, several studies show a dramatic decrease in gene expression over the last two genes of the respiratory syncytial virus (RSV) genome (a highly studied NNSV). The textbook model cannot explain these phenomena.

Methods: Computational models of RSV and vesicular stomatitis virus (VSV – another highly studied NNSV) transcription were written in the Python programming language using the Scientific Python Development Environment. The model code is freely available on GitHub: …

An Implementation Of The Method Of Moments On Chemical Systems With Constant And Time-Dependent Rates, Emmanuel O. Adara, Roger B. Sidje

Northeast Journal of Complex Systems (NEJCS)

Among numerical techniques used to facilitate the analysis of biochemical reactions, we can use the method of moments to directly approximate statistics such as the mean numbers of molecules. The method is computationally viable in time and memory, compared to solving the chemical master equation (CME) which is notoriously expensive. In this study, we apply the method of moments to a chemical system with a constant rate representing a vascular endothelial growth factor (VEGF) model, as well as another system with time-dependent propensities representing the susceptible, infected, and recovered (SIR) model with periodic contact rate. We assess the accuracy of …

Predicting Marine Teleost Responses To Ocean Warming And Pollution, Akila Harishchandra

Electronic Theses and Dissertations

Ocean warming and pollution are two detrimental anthropogenic factors causing rapid marine ecosystem degradation recorded in the past decades. These factors alter the marine environment intolerable for many marine species, forcing them to either adapt or shift their contemporary habitat ranges to reduce the extinction risk embedded with environmental degradation. Estimating marine species’ habitat range shifts, and their potential for developing adaptive mechanisms are critical for ecosystem conservation and management, human health risk assessment, and climate change vulnerability assessments. Given that, for the first chapter of this thesis, we focused on developing a species distribution model (SDM) integrating marine species …

Genome-Scale Methylation Analysis In Blood And Tumor Identifies Immune Profile, Age Acceleration, And Dna Methylation Alterations Associated With Bladder Cancer Outcomes, Ji-Qing Chen

Dartmouth College Ph.D Dissertations

Bladder cancer patients receive frequent screening due to the high tumor recurrence rate (more than 60%). Nowadays, the conventional monitoring method relies on cystoscopy which is highly invasive and increases patient morbidity and burden to the health care system with frequent follow-up. As a result, it is urgent to explore novel markers related to the outcomes of bladder cancer. Immune profiles have been associated with cancer outcomes and may have the potential to be biomarkers for outcomes management. However, little work has been conducted to investigate the associations of immune cell profiles with bladder cancer outcomes. Here, I utilized the …

Computational Analysis Of Antibody Binding Mechanisms To The Omicron Rbd Of Sars-Cov-2 Spike Protein: Identification Of Epitopes And Hotspots For Developing Effective Therapeutic Strategies, Mohammed Alshahrani

Computational and Data Sciences (PhD) Dissertations

The advent of the Omicron strain of SARS-CoV-2 has elicited apprehension regarding its potential influence on the effectiveness of current vaccines and antibody treatments. The present investigation involved the implementation of mutational scanning analyses to examine the impact of Omicron mutations on the binding affinity of four categories of antibodies that target the Omicron receptor binding domain (RBD) of the Spike protein. The study demonstrates that the Omicron variant harbors 23 unique mutations across the RBD regions I, II, III, and IV. Of these mutations, seven are shared between RBD regions I and II, while three are shared among RBD …

Annotation Of Non-Model Species’ Genomes, Taiya Jarva

Master's Theses

The innovations in high throughput sequencing technologies in recent decades has allowed unprecedented examination and characterization of the genetic make-up of both model and non-model species, which has led to a surge in the use of genomics in fields which were previously considered unfeasible. These advances have greatly expanded the realm of possibilities in the fields of ecology and conservation. It is now possible to the identification of large cohorts of genetic markers, including single nucleotide polymorphisms (SNPs) and larger structural variants, as well as signatures of selection and local adaptation. Markers can be used to identify species, define population …

Exploring The Interactions Between Sars-Cov-2 And Host Proteins., Sojan Shrestha

School of Biological Sciences: Dissertations, Theses, and Student Research

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the current pandemic, Coronavirus Disease 2019 (COVID-19). SARS-CoV-2 is considered to be of zoonotic origin; it originated in non-human animals and was transmitted to humans. Since the early stage of the pandemic, however, the evidence of transmissions from humans to animals (reverse zoonoses) has been found in multiple animal species including mink, white-tailed deer, and pet and zoo animals. Furthermore, secondary zoonotic events of SARS-CoV-2, transmissions from animals to humans, have been also reported. It is suggested that non-human hosts can act as SARS-CoV-2 reservoirs where accumulated …

Exploration Of The Immune Landscape Of Ebv-Associated Gastric Cancers, Mikhail Salnikov

Electronic Thesis and Dissertation Repository

Epstein–Barr virus (EBV) is a gammaherpesvirus associated with 9% of all gastric cancers (GCs). EBV-associated GCs (EBVaGCs) are pathologically and clinically distinct entities from EBV-negative GCs (EBVnGCs), with EBVaGCs exhibiting differential molecular pathology and patient prognosis. The purpose of this thesis is to investigate the tumor microenvironment (TME) of EBVaGCs, which has not been explored in-depth. We hypothesize that EBVaGCs and EBVnGCs are also distinct in terms of the molecular immune landscape. We employed over 400 stomach adenocarcinoma (STAD) samples from The Cancer Genome Atlas (TCGA), as well as a single cell dataset, for the construction of a web suite …

Mining Sars-Cov-2 Phylogenetic Trees To Estimate Circulating Infections And Patterns Of Migration, Erin V. Brintnell

Electronic Thesis and Dissertation Repository

The SARS-CoV-2 pandemic led to the formation of very large databases of genomic viral data. These databases contain information on transmission dynamics, emergence and evolution of SARS-CoV-2. However, extracting this information from sequences is difficult, as most methods of analyzing viral genomes were developed for smaller data sets. Therefore, my objective was to develop new fast estimators of the number of infections (I) and the rate of migration based on simple features of SARS-CoV-2 phylogenies.

I simulated pathogen evolution using a susceptible-exposed-infectious-recovered (SEIR) model of pathogen spread, reconstructing evolution using CoVizu. For simulations of I, I varied the total number …

Machine Learning And Network Embedding Methods For Gene Co-Expression Networks, Niloofar Aghaieabiane

Dissertations

High-throughput technologies such as DNA microarrays and RNA-seq are used to measure the expression levels of large numbers of genes simultaneously. To support the extraction of biological knowledge, individual gene expression levels are transformed into Gene Co-expression Networks (GCNs). GCNs are analyzed to discover gene modules. GCN construction and analysis is a well-studied topic, for nearly two decades. While new types of sequencing and the corresponding data are now available, the software package WGCNA and its most recent variants are still widely used, contributing to biological discovery.

The discovery of biologically significant modules of genes from raw expression data is …

Integrating Omim And Intact Data For The Analysis Of Gene-Phenotype Interactions In Complex Diseases: A Linux-Based Computational Tool For Network Analysis, Devin Keane

All Theses

The field of genetics is constantly evolving. New advances in bioinformatics and computational approaches are leading to exciting new developments in our ability to treat and prevent diseases. Computational genetics provides valuable insights into the complex mechanisms and layers of biological communication that shape an organism's phenotype. Understanding these mechanisms is critical to advancing human health.

The study of diseases in genetics requires a comprehensive understanding of the interactions between various biological processes, including gene expression, protein synthesis, RNA, metabolism, and cell-cell communication. To effectively address the root causes of such diseases, multi-disciplinary approaches that integrate information from different levels …

Clustering And Analysis Of G Quadruplex Sequences., Aryan Neupane

Electronic Theses and Dissertations

G quadruplex structures are secondary structures located throughout the genome of various organisms with involvement in regulatory functions in different transcription, translation, genome stability, epigenetic regulation as well as cell division. Even with the diverse acknowledgement of G4 structure in vivo, there are no current search tools for G quadruplexes based on already identified G quadruplexes and identified families across different genomes based on sequence diversity. Construction of families of G4 sequences and identifying their polymorphisms within disease and disorders will lead to a better understanding of their functional roles and will further research into the biophysical modeling of interactions …

Acetate Metabolism In The Fungal Pathogen Cryptococcus Neoformans, Oly Ahmed

All Dissertations

Cryptococcus neoformans is an environmental basidiomycetous fungus with a worldwide distribution and a wide range of habitats. Inhalation of the desiccated yeasts or spores of C. neoformans often leads to opportunistic pulmonary infections in immunocompromised individuals, and in severe cases causes lethal meningitis following hematogenous dissemination. During infection, depending on the tissue and disease state, the invading fungi experience a range of nutrient microenvironments within the host body. As a result, rapid metabolic adaptations geared towards efficient utilization of carbon sources alternative to glucose become one of the prime determinants of survival and growth for the pathogen. Incidentally, cryptococcal infection …

Pirna Expression In Regenerative Tissue Of Octopus Bimaculoides, Bailey Ervin

Honors Theses

Tissue regeneration is present in varying capacities across the animal kingdom. Animals such as Hydra and planarians have the capacity to regenerate entire bodies from extremely small sections of amputated tissue. Others, such as humans, have restricted capacities of regeneration, especially in terms of full appendages and specialized tissues such as cardiac and nervous tissue. One of the primary goals of studying regeneration in other organisms is to achieve the development of regenerative medicine. Interaction of P-element induced WImpy testis (PIWI) proteins and PIWI-interacting RNAs (piRNAs) have been implicated in germline genome maintenance, as well as transposable element silencing. Research …

Pirna Expression In The Tube Feet Of Lytechinus Variegatus, Reagan Milliet

Honors Theses

Tissue regeneration is an area of research with implications for medicine and animal health. While nearly all living multi-cellular organisms are capable of regeneration, there are major differences in the animal kingdom. Some organisms are capable of regenerating virtually every cell in their bodies. In hopes of engineering tissue regeneration for medical applications, the mechanisms by which organisms regenerate are being widely investigated. To better understand regeneration, the role of P-element Induced WImpy testis (PIWI) proteins are being evaluated. In collaboration with PIWIinteracting RNAs (piRNAs), PIWI proteins have been proven instrumental to transposon silencing and maintenance of the genome in …

Reconstructing Mutational Lineages In Breast Cancer By Multi-Patient-Targeted Single Cell Dna Sequencing, Jake Leighton

Dissertations and Theses (Open Access)

Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer with high rates of metastasis and recurrence, where TNBC patients have a poor 5-year survival and ~50% are non-responsive to chemotherapy. Aneuploidy is a cancer hallmark that is pervasive in over 90% of breast cancer patients and is indicative of complex genomic rearrangements that are acquired during tumor initiation. Although copy number aberrations have been extensively studied in relation to aneuploidy and TNBC initiation, little is currently known regarding the timing and impact of single nucleotide variants (SNVs) contributing to these early transformative genomic events. Paramount to novel …