Life Sciences Commons^™

Combining The Tyrosine Kinase Inhibitor Cabozantinib And The Mtorc1/2 Inhibitor Sapanisertib Blocks Erk Pathway Activity And Suppresses Tumor Growth In Renal Cell Carcinoma, Yige Wu, Siqi Chen, Xiaolu Yang, Kazuhito Sato, Preet Lal, Yuefan Wang, Andrew T Shinkle, Michael C Wendl, Tina M Primeau, Yanyan Zhao, Alanna Gould, Hua Sun, Jacqueline L Mudd, Jeremy Hoog, R Jay Mashl, Matthew A Wyczalkowski, Chia-Kuei Mo, Ruiyang Liu, John M Herndon, Sherri R Davies, Di Liu, Xi Ding, Yvonne A Evrard, Bryan E Welm, David Lum, Mei Yee Koh, Alana L Welm, Jeffrey H Chuang, Jeffrey A Moscow, Funda Meric-Bernstam, Ramaswamy Govindan, Shunqiang Li, James Hsieh, Ryan C Fields, Kian-Huat Lim, Cynthia X Ma, Hui Zhang, Li Ding, Feng Chen

Faculty, Staff and Student Publications

Current treatment approaches for renal cell carcinoma (RCC) face challenges in achieving durable tumor responses due to tumor heterogeneity and drug resistance. Combination therapies that leverage tumor molecular profiles could offer an avenue for enhancing treatment efficacy and addressing the limitations of current therapies. To identify effective strategies for treating RCC, we selected ten drugs guided by tumor biology to test in six RCC patient-derived xenograft (PDX) models. The multitargeted tyrosine kinase inhibitor (TKI) cabozantinib and mTORC1/2 inhibitor sapanisertib emerged as the most effective drugs, particularly when combined. The combination demonstrated favorable tolerability and inhibited tumor growth or induced tumor …

Plants As Vectors For Environmental Prion Transmission, Christina M Carlson, Samuel Thomas, Matthew W Keating, Paulina Soto, Nicole M Gibbs, Haeyoon Chang, Jamie K Wiepz, Annabel G Austin, Jay R Schneider, Rodrigo Morales, Christopher J Johnson, Joel A Pedersen

Faculty, Staff and Student Publications

Prions cause fatal neurodegenerative diseases and exhibit remarkable durability, which engenders a wide array of potential exposure scenarios. In chronic wasting disease of deer, elk, moose, and reindeer and in scrapie of sheep and goats, prions are transmitted via environmental routes and the ability of plants to accumulate and subsequently transmit prions has been hypothesized, but not previously demonstrated. Here, we establish the ability of several crop and other plant species to take up prions via their roots and translocate them to above-ground tissues from various growth media including soils. We demonstrate that plants can accumulate prions in above-ground tissues …

Bayesian Longitudinal Tensor Response Regression For Modeling Neuroplasticity, Suprateek Kundu, Alec Reinhardt, Serena Song, Joo Han, M Lawson Meadows, Bruce Crosson, Venkatagiri Krishnamurthy

Faculty, Staff and Student Publications

A major interest in longitudinal neuroimaging studies involves investigating voxel-level neuroplasticity due to treatment and other factors across visits. However, traditional voxel-wise methods are beset with several pitfalls, which can compromise the accuracy of these approaches. We propose a novel Bayesian tensor response regression approach for longitudinal imaging data, which pools information across spatially distributed voxels to infer significant changes while adjusting for covariates. The proposed method, which is implemented using Markov chain Monte Carlo (MCMC) sampling, utilizes low-rank decomposition to reduce dimensionality and preserve spatial configurations of voxels when estimating coefficients. It also enables feature selection via joint credible …

Mitochondrial Metabolism In Blood More Reliably Predicts Whole-Animal Energy Needs Compared To Other Tissues, Stefania Casagrande, Maciej Dzialo, Lisa Trost, Kasja Malkoc, Edyta T. Sadowska, Michaela Hau, Barbara J. Pierce, Scott R. Mcwilliams, Ulf Bauchinger

Biology Faculty Publications

Understanding energy metabolism in free-ranging animals is crucial for ecological studies. In birds, red blood cells (RBCs) offer a minimally invasive method to estimate metabolic rate (MR). In this study with European starlings Sturnus vulgaris, we examined how RBC oxygen consumption relates to oxygen use in key tissues (brain, liver, heart, and pectoral muscle) and versus the whole-organism measured at basal levels. The pectoral muscle accounted for 34-42% of organismal MR, while the heart and liver, despite their high mass-specific metabolic rate, each contributed 2.5-3.0% to organismal MR. Despite its low contribution to organismal MR (0.03-0.04%), RBC MR best predicted …

Advances In Diagnostic Tools And Therapeutic Approaches For Gliomas: A Comprehensive Review, Gayathree Thenuwara Nanolab Research Centre, James Curtin, Furong Tian Nanolab Research Centre

Articles

Gliomas, a prevalent category of primary malignant brain tumors, pose formidable clinical challenges due to their invasive nature and limited treatment options. The current therapeutic landscape for gliomas is constrained by a “one-size-fits-all” paradigm, significantly restricting treatment efficacy. Despite the implementation of multimodal therapeutic strategies, survival rates remain disheartening. The conventional treatment approach, involving surgical resection, radiation, and chemotherapy, grapples with substantial limitations, particularly in addressing the invasive nature of gliomas. Conventional diagnostic tools, including computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET), play pivotal roles in outlining tumor characteristics. However, they face limitations, such as …

Differences In Set-Based Tests For Sparse Alternatives When Testing Sets Of Outcomes Compared To Sets Of Explanatory Factors In Genetic Association Studies, Ryan Sun, Andy Shi, Xihong Lin

Faculty, Staff and Student Publications

Set-based association tests are widely popular in genetic association settings for their ability to aggregate weak signals and reduce multiple testing burdens. In particular, a class of set-based tests including the Higher Criticism, Berk-Jones, and other statistics have recently been popularized for reaching a so-called detection boundary when signals are rare and weak. Such tests have been applied in two subtly different settings: (a) associating a genetic variant set with a single phenotype and (b) associating a single genetic variant with a phenotype set. A significant issue in practice is the choice of test, especially when deciding between innovated and …

Acidosis-Mediated Increase In Ifn-Γ-Induced Pd-L1 Expression On Cancer Cells As An Immune Escape Mechanism In Solid Tumors, Philipp Knopf, Dimitri Stowbur, Sabrina H L Hoffmann, Natalie Hermann, Andreas Maurer, Valentina Bucher, Marilena Poxleitner, Bredi Tako, Dominik Sonanini, Balaji Krishnamachary, Sanhita Sinharay, Birgit Fehrenbacher, Irene Gonzalez-Menendez, Felix Reckmann, David Bomze, Lukas Flatz, Daniela Kramer, Martin Schaller, Stephan Forchhammer, Zaver M Bhujwalla, Leticia Quintanilla-Martinez, Klaus Schulze-Osthoff, Mark D Pagel, Marieke F Fransen, Martin Röcken, André F Martins, Bernd J Pichler, Kamran Ghoreschi, Manfred Kneilling

Faculty, Staff and Student Publications

Immune checkpoint inhibitors have revolutionized cancer therapy, yet the efficacy of these treatments is often limited by the heterogeneous and hypoxic tumor microenvironment (TME) of solid tumors. In the TME, programmed death-ligand 1 (PD-L1) expression on cancer cells is mainly regulated by Interferon-gamma (IFN-γ), which induces T cell exhaustion and enables tumor immune evasion. In this study, we demonstrate that acidosis, a common characteristic of solid tumors, significantly increases IFN-γ-induced PD-L1 expression on aggressive cancer cells, thus promoting immune escape. Using preclinical models, we found that acidosis enhances the genomic expression and phosphorylation of signal transducer and activator of transcription …

Living Among Wildlife: Elevating Human-Wildlife Interactions And Coexistence, Bridget Rebecca Murphy

Graduate Student Portfolios, Professional Papers, and Capstone Projects

After a semester of learning, both in class and in nature, my writing honed in further on this human-nature divide. To me, I see humans as part of nature – as we are mammals, animals, part of the food chain, biological beings no higher than others on our planet. We have simply constructed this false narrative around us within our societies, minds and media that embeds this division between us and nature, between us and wildlife. Humans have been managing, stewarding, living off and within landscapes for thousands of years. As time and technology evolved, a lot of people began …

Monitoring Time Domain Characteristics Of Parkinson's Disease Using 3d Memristive Neuromorphic System, Md Abu Bakr Siddique, Yan Zhang, Hongyu An

Michigan Tech Publications

INTRODUCTION: Parkinson's disease (PD) is a neurodegenerative disorder affecting millions of patients. Closed-Loop Deep Brain Stimulation (CL-DBS) is a therapy that can alleviate the symptoms of PD. The CL-DBS system consists of an electrode sending electrical stimulation signals to a specific region of the brain and a battery-powered stimulator implanted in the chest. The electrical stimuli in CL-DBS systems need to be adjusted in real-time in accordance with the state of PD symptoms. Therefore, fast and precise monitoring of PD symptoms is a critical function for CL-DBS systems. However, the current CL-DBS techniques suffer from high computational demands for real-time …

Habitat And Demography Of The Ozark Chinquapin (Castanea Ozarkensis) At Roaring River State Park In Barry County, Missouri, Danielle Evilsizor

Electronic Theses & Dissertations

The Ozark chinquapin, Castanea ozarkensis Ashe, is a chestnut tree with a range concentrated in the Interior Highlands of North America. Like other North American members of Castanea, it was reduced from an overstory tree to an understory shrub by the invasive chestnut blight fungus (Cryphonectria parasitica [Murrill] M.E. Barr) during the early 20^th century. However, relatively little is known about the habitat of this species or its health and reproductive capability post chestnut blight. Chapter one of this study analyzed the habitat of this species through a random forest species distribution model (SDM) to predict where …

Role Of The Ganglioside Gd2 And Its Biosynthetic Enzyme Gd3 Synthase In Prostate Cancer Tumorigenesis, Aaqib Bhat

Theses & Dissertations

Despite significant advancements in managing localized prostate cancer (PC), which have notably increased survival rates, advanced PC continues to be a leading cause of cancer- related fatalities. The discovery of new pathways that can be targeted to inhibit tumor growth in PC could pave the way for innovative treatment strategies. The disialylganglioside GD2 is an FDA-approved target for antibody therapies in neuroblastoma and has not been extensively studied in the context of PC. The work done in this thesis reveals that GD2 is present on a minor subset of PC cells in certain patients and is more prevalent in metastatic …

Gpr84-Mediated Signal Transduction Affects Metabolic Function By Promoting Brown Adipocyte Activity, Xue-Nan Sun, Yu A An, Vivian A Paschoal, Camila O De Souza, May-Yun Wang, Lavanya Vishvanath, Lorena Ma Bueno, Ayanna S Cobb, Joseph A Nieto Carrion, Madison E Ibe, Chao Li, Harrison A Kidd, Shiuhwei Chen, Wenhong Li, Rana K Gupta, Da Young Oh

Faculty, Staff and Student Publications

The G protein-coupled receptor 84 (GPR84), a medium-chain fatty acid receptor, has garnered attention because of its potential involvement in a range of metabolic conditions. However, the precise mechanisms underlying this effect remain elusive. Our study has shed light on the pivotal role of GPR84, revealing its robust expression and functional significance within brown adipose tissue (BAT). Mice lacking GPR84 exhibited increased lipid accumulation in BAT, rendering them more susceptible to cold exposure and displaying reduced BAT activity compared with their WT counterparts. Our in vitro experiments with primary brown adipocytes from GPR84-KO mice revealed diminished expression of thermogenic genes …

Wind Erosion After Fire In Western Australia - Frequently Asked Questions (Faqs), Department Of Primary Industries And Regional Development, Western Australia

Natural resources factsheets

These are some common questions after serious fires in the agricultural areas of south-west Western Australia. Staff of the Department of Primary Industries and Regional Development (DPIRD), agronomists and farmers with experience have contributed to the answers.

Please note that these answers are general in nature, and land managers wanting advice for a specific property will need to ask local professionals or experienced land managers.

For more information about recovering from fire and wind erosion, see the DPIRD website.

Exploring The Microbial Diversity And Characterization Of Cellulase And Hemicellulase Genes In Goat Rumen: A Metagenomic Approach, Santosh Thapa, Suping Zhou, Joshua O’Hair, Kamal Al Nasr, Alexander Ropelewski, Hui Li

Agricultural and Environmental Sciences Faculty Research

Background

Goat rumen microbial communities are perceived as one of the most potential biochemical reservoirs of multi-functional enzymes, which are applicable to enhance wide array of bioprocesses such as the hydrolysis of cellulose and hemi-cellulose into fermentable sugar for biofuel and other value-added biochemical production. Even though, the limited understanding of rumen microbial genetic diversity and the absence of effective screening culture methods have impeded the full utilization of these potential enzymes. In this study, we applied culture independent metagenomics sequencing approach to isolate, and identify microbial communities in goat rumen, meanwhile, clone and functionally characterize novel cellulase and xylanase …

Mapping Restricted Introgression Across The Genomes Of Admixed Indigenous African Cattle Breeds., Juliane Friedrich, Richard I Bailey, Andrea Talenti, Umer Chaudhry, Qasim Ali, Emmanuel F Obishakin, Chukwunonso Ezeasor, Jessica Powell, Olivier Hanotte, Abdulfatai Tijjani, Karen Marshall, James Prendergast, Pamela Wiener

Faculty Research 2023

BACKGROUND: The genomes of indigenous African cattle are composed of components with Middle Eastern (taurine) and South Asian (indicine) origins, providing a valuable model to study hybridization and to identify genetic barriers to gene flow. In this study, we analysed indigenous African cattle breeds as models of hybrid zones, considering taurine and indicine samples as ancestors. In a genomic cline analysis of whole-genome sequence data, we considered over 8 million variants from 144 animals, which allows for fine-mapping of potential genomic incompatibilities at high resolution across the genome.

RESULTS: We identified several thousand variants that had significantly steep clines ('SCV') …

A Year Of Wins For Farmed Animals, Lewis Bollard

General – Farm Animal Issues

Although the European Union shelved its ambitious farmed animal welfare reforms, there were other “wins” for farmed animals in 2023. There were 130 new corporate pledges to eliminate cages for laying hens and the worst abuses of broiler chickens. So far, over 1,000 corporate pledges have been fully implemented, and 39% of American hens, 60% of European hens, and 80% of British hens are cage-free, up from 6%, 41%, and 48%, respectively, a decade ago. The US Supreme Court upheld California’s Proposition 12, which bans the sale of eggs, pork, and veal from caged animals and their offspring in California. …

A Year Of Wins For Farmed Animals, Lewis Bollard

Nexus – UNEP – Animal Welfare, Environment, Sustainable Development

Although the European Union shelved its ambitious farmed animal welfare reforms, there were other “wins” for farmed animals in 2023. There were 130 new corporate pledges to eliminate cages for laying hens and the worst abuses of broiler chickens. So far, over 1,000 corporate pledges have been fully implemented, and 39% of American hens, 60% of European hens, and 80% of British hens are cage-free, up from 6%, 41%, and 48%, respectively, a decade ago. The US Supreme Court upheld California’s Proposition 12, which bans the sale of eggs, pork, and veal from caged animals and their offspring in California. …

Review: The Harvesting Process And Recent Advances On Health Benefits Of White Tea, Adhi Irianto Mastur, Agung Karuniawan, Ernah

Jurnal Kultivasi

The meticulous harvesting process and appropriate post-harvest techniques play pivotal roles in preserving the quality and health benefits of white tea. This careful approach maintains the bioactive compounds such as polyphenols, caffeine, gallic acid, Epigallocationchin (EGC), Epigallocationchin gallate (EGCG), and Epicatechin gallate (ECG), integral to white tea's health benefits. The stability of catechin content in tea plants is greatly influenced by the environment (clone, plant age, leaf age, altitude, temperature, humidity, processing, and pH when storing dry tea). In Indonesia, the raw materials used to produce white tea are mostly pecco from the superior GMB clone Assamica variety which has …

Salamander Modeling: Bridging The Gaps In Environmental Science Accessibility, Grace Leopold

Honors Program Theses and Projects

In the realm of science education, ensuring inclusivity and accessibility for all students, especially those with Individualized Education Programs (IEPs), is an imperative goal. IEPs are customized plans designed to support students with diverse learning needs, which can encompass a broad spectrum of disabilities and learning differences (Shaw, 2021). Providing learners with an IEP is an integral part of Special Education, however, there are a host of overarching challenges faced by students with IEPs in science education, especially in environmental science classes. In this thesis, the development and application of clay salamander models are evaluated for their potential to provide …

Tropicalization Fact Sheet, Linda Walters, Carla Perscky

CEELAB Outreach Materials

The goal of this 2-sided fact sheet is to introduce the topic of tropicalization along our coastlines to young audiences and their families. Tropicalization is defined as, "the transformation of ecosystems by tropical organisms that migrate towards the poles in response to warming minimum winter temperatures."

Population Trends And Trophic Ecology Of The Invasive Peacock Eel (Macrognathus Siamensis) In The Florida Everglades, Grace Kahmann

Electronic Theses and Dissertations

Invasive species threaten the ecological integrity of ecosystems worldwide, including the Florida Coastal Everglades. This study investigated the ecological role of the peacock eel (Macrognathus siamensis) within this ecosystem, emphasizing its population trends and the environmental factors that affect its population performance, and the potential for interactions with native fish assemblages and coastal food webs. I used 19 years of electrofishing data to investigate the population trends of peacock eels at the marsh-mangrove ecotone of the Shark River Estuary, Everglades National Park (Florida, USA). I found that peacock eel populations have increased since their first detection in 2002, and their …

Plant Material Selection And Seed Enhancement Technologies Improve Seed-Based Restoration In Dryland Systems, Travis G. Sowards

Theses and Dissertations

The restoration of large-scale heterogeneous landscapes is typically approached using seed-based restoration as a cost-effective means to achieve project goals and objectives. However, seeding is often met with low survival rates primarily driven by low seedling emergence and establishment. This dissertation investigates opportunities to enhance restoration focusing on 1) seed treatments, 2) plant materials, and 3) a synthesis of seeding strategies. • Fungal pathogenesis can cause high seedling mortality. Fungicide seed coatings used in the agriculture industry are novel to wildland restoration. We assess the effect a fungicide seed coating has on the recruitment of Pseudoroegneria spicata seedlings across a …

Understanding And Combating The Spread Of Antibiotic-Resistant Organisms, Bejan Mahmud

Arts & Sciences Graduate Student Theses and Dissertations

The introduction of antibiotics in the 20th century stands as one of our greatest scientific achievements, profoundly transforming human health and global well-being. Over the past century, antibiotics have ensured that infectious diseases are no longer the most common causes of death worldwide. In further enabling a vast array of invasive medical procedures (e.g., surgeries, organ transplants), antibiotics have effectively added decades to the average human lifespan. In agriculture, antibiotics have been heavily relied upon to meet the nutritional demands of the growing human population. Thus, ever since the introduction of penicillin, antibiotics have been the “miracle drugs” they were …

Adaptation Of Several Hybrid Maize In West Nusa Tenggara Drylands Using Modified Plant Spacing For Optimal Seed And Biomass Productions, Karlina Syahruddin, Suwardi, Slamet Bambang Priyanto, Roy Efendi, Herawati, Abdul Fattah, Rahman, Hasbi, Aminah, Fatmawati, Sigit Budi Santoso, Lesty Ayu Bidhari, Muhammad Abid

Jurnal Kultivasi

Maize is a crucial multipurpose strategic food crop in Indonesia. Land expansion employing dry land, row-space technology, and suitable varieties, is emerging as the solution to fulfill the rising need for seeds and biomass. The study was carried out from August to December using a factorial randomized block design consisting of two treatment factors, namely the treatment factor of 6 varieties and 2 row-spacings, to verify the new superior hybrid maize, which is adaptable in dry land Senayan village, Poto Tano sub-district, West Sumbawa district, and West Nusa Tenggara (NTB). The results showed that JH 37 and JH 29 varieties …

Recombination-Mediated Dissemination Of Methicillin-Resistant S Aureus Clonal Complex 1 In The Egyptian Health Care Settings, Salma W Elsayed, Reem A Elghaish, Eman Badr, Shaimaa F Mouftah, Nehal A Saif, Iman S Naga, Ahmed H Shata, Ben Pascoe, Samuel K Sheppard, Mohamed Elhadidy

Faculty, Staff and Student Publications

Background: Methicillin-resistant Staphylococcus aureus (MRSA) is a rapidly evolving pathogen that is frequently associated with outbreaks and sustained epidemics. This study investigated the population structure, resistome, virulome, and the correlation between antimicrobial resistance determinants with phenotypic resistance profiles of 36 representative hospital-acquired MRSA isolates recovered from hospital settings in Egypt.

Results: The community-acquired MRSA lineage, clonal complex 1 (CC1) was the most frequently detected clone, followed by three other globally disseminated clones, CC121, CC8, and CC22. Most isolates carried SCCmec type V and more than half of isolates demonstrated multi-drug resistant phenotypes. Resistance to linezolid, a last resort antibiotic for …

Evaluation Of The Aggressive-Variant Prostate Cancer Molecular Signature In Clinical Laboratory Improvement Amendments (Clia) Environments, Paul V Viscuse, Rebecca S Slack-Tidwell, Miao Zhang, Prih Rohra, Keyi Zhu, F Anthony San Lucas, Eric Konnick, Patrick G Pilie, Bilal Siddiqui, Christopher J Logothetis, Paul Corn, Sumit K Subudhi, Colin C Pritchard, Rama Soundararajan, Ana Aparicio

Faculty, Staff and Student Publications

Aggressive-variant prostate cancers (AVPCs) are a subset of metastatic castrate-resistant prostate cancers (mCRPCs) characterized by defects in ≥ two of three of TP53, RB1, and PTEN (AVPCm), a profile linked to lineage plasticity, androgen indifference, and platinum sensitivity. Men with mCRPC undergoing biopsies for progression were assessed for AVPCm using immunohistochemistry (IHC), next-generation sequencing (NGS) of solid tumor DNA (stDNA), and NGS of circulating tumor DNA (ctDNA) assays in CLIA-certified labs. Biopsy characteristics, turnaround times, inter-reader concordance, and inter-assay concordance were assessed. AVPCm was detected in 13 (27%) patients via IHC, two (6%) based on stDNA, and seven …

Shallot Cultivation Originated From True Shallot Seed (Tss) On Andisols Enriched With Various Ameliorants, Fahmi Aprianto, Mahfud Arifin, Emma Trinurani Sofyan

Jurnal Kultivasi

Application of soil ameliorants is important to improve Andisols properties and increase shallot productivity. The research objective is to determine the kind of ameliorant which the best effect on the growth and productivity of shallots originating from TSS in Andisols Lembang, West Java. The experiment was conducted in Margahayu Research Station, Lembang, West Java from January to May 2021. A randomized block design (RBD) with 6 treatments and 5 replications was set up in the field. Treatments include control (no ameliorant), 20 tons/ha of horse manure, 10 tons/ha of rice straw compost, 10 tons/ha of bamboo leaf compost, 10 tons/ha …

Gap Junctions Or Hemichannel-Dependent And Independent Roles Of Connexins In Fibrosis, Epithelial-Mesenchymal Transitions, And Wound Healing, Yuting Li, Francisca M Acosta, Jean X Jiang

Faculty, Staff and Student Publications

Fibrosis initially appears as a normal response to damage, where activated fibroblasts produce large amounts of the extracellular matrix (ECM) during the wound healing process to assist in the repair of injured tissue. However, the excessive accumulation of the ECM, unresolved by remodeling mechanisms, leads to organ dysfunction. Connexins, a family of transmembrane channel proteins, are widely recognized for their major roles in fibrosis, the epithelial-mesenchymal transition (EMT), and wound healing. Efforts have been made in recent years to identify novel mediators and targets for this regulation. Connexins form gap junctions and hemichannels, mediating communications between neighboring cells and inside …

Investigating The Role Of Bhlhe40 In Host Responses To Mycobacterium Tuberculosis Infection And Myeloid Cell Development, Skyler Hendrix

Arts & Sciences Graduate Student Theses and Dissertations

Infections with Mycobacterium tuberculosis (Mtb), the causative agent of the disease tuberculosis (TB), remain a prominent global health threat that affects millions of people annually. While antibiotic treatments for Mtb infections are available, the increased prevalence of drug-resistant Mtb cases has highlighted the urgent need to develop additional therapeutic options such as host-directed therapies. Development of host-directed therapies, however, first requires a better understanding of the protective immune responses required to control Mtb infection. Such responses must strike a precise balance between pro-inflammatory and anti-inflammatory responses that promote bacterial clearance while also minimizing tissue damage. Here we show that the …

Construction Of A Human Pangenome Reference To Improve Structural Variation Detection, Wen-Wei Liao

Arts & Sciences Graduate Student Theses and Dissertations

Structural variants (SVs) significantly contribute to genetic diversity among individuals and impact gene regulation, disease, and evolution. The predominant approach to profiling these genetic variants in large-scale population studies is through short-read whole-genome sequencing (WGS). This approach involves sequencing millions of short reads, aligning them to a linear reference genome, and subsequently identifying variants relative to this reference. However, its capability to detect SVs, especially long insertions and complex rearrangements, is limited. The primary limitation arises from the insufficient representation of structural diversity across human populations in the linear reference genome. As a result, short reads derived from non-reference SVs …