Genetics and Genomics Commons^™

Therapeutic Potential Of Astrocyte-Derived Extracellular Vesicles In Mitigating Cytotoxicity And Transcriptome Changes In Human Brain Endothelial Cells, Ruth Juliana Stewart

Doctoral Dissertations

Extracellular vesicles (EVs) play a major role in cell-to-cell communication via the horizontal transfer of RNA, DNA, proteins, and lipids that affect the physiological response of the recipient cells. Astrocytes are a type of glial cell that exerts a protective effect on neurons and brain endothelial cells. The astrocytes and the endothelial cells form the blood-brain barrier. Due to their nano-size and non-complex structure, EVs can efficiently cross the blood-brain barrier. This study investigated and assessed the impact of EVs on reducing oxidative DNA damage in human brain endothelial cells (HBECs). The protective potential of astrocyte-derived EVs was determined by …

Multi-Decadal Aspen Dynamics Show Recruitment Bottleneck Across Complex Mountain Community, Michael T. Stoddard, Kyle C. Rodman, Connor D. Crouch, David W. Huffman, Peter Z. Fulé, Kristen M. Waring, Margaret M. Moore

Aspen Bibliography

Changes in forest structure and shifts in tree species composition have occurred globally due to climate change and altered disturbance regimes. With climate trending toward warmer and drier conditions, these altered forest communities may reorganize in diverse and unpredictable ways. This is especially true in mountain environments where a range of vegetation types and abiotic conditions coexist. In this study, we used long-term permanent plot data from a site spanning broad environmental gradients to assess regeneration and mortality patterns in populations of aspen (Populus tremuloides). The study site, located on the San Francisco Peaks, Arizona, USA, is near …

Sample Multiplexing For Retinal Single-Cell Rna Sequencing, Justin Ma, Ting-Kuan Chu, Maria Polo-Prieto, Yong H Park, Yumei Li, Rui Chen, Graeme Mardon, Benjamin J Frankfort, Nicholas M Tran

Faculty, Staff and Students Publications

Rare cell populations can be challenging to characterize using microfluidic single-cell RNA sequencing (scRNA-seq) platforms. Typically, the population of interest must be enriched and pooled from multiple biological specimens for efficient collection. However, these practices preclude the resolution of sample origin together with phenotypic data and are problematic in experiments in which biological or technical variation is expected to be high (e.g., disease models, genetic perturbation screens, or human samples). One solution is sample multiplexing whereby each sample is tagged with a unique sequence barcode that is resolved bioinformatically. We have established a scRNA-seq sample multiplexing pipeline for mouse retinal …

Analyzing And Extending Machine Learning Frameworks On High Risk Domains, Chengbin Hu

USF Tampa Graduate Theses and Dissertations

Machine learning (ML) has become a transformative force in high-risk domains such as genomics and cybersecurity, where accurate predictions and robust defenses are essential. This dissertation advances ML frameworks in these areas by developing methods to enhance predictive power in health applications and assess vulnerabilities in machine learning systems.

In the genomics field, the work addresses challenges in Non-Invasive Prenatal Testing (NIPT) of monogenic disorders by proposing a deep learning model that reconstructs the fetal genome using maternal plasma cell-free DNA (cfDNA) and parental whole-genome sequencing (WGS) data. This model achieves high accuracy in single nucleotide variation (SNV) prediction, surpassing …

Long-Read Sequencing Of An Advanced Cancer Cohort Resolves Rearrangements, Unravels Haplotypes, And Reveals Methylation Landscapes, Kieran O'Neill, Erin Pleasance, Jeremy Fan, Vahid Akbari, Glenn Chang, Katherine Dixon, Veronika Csizmok, Signe Maclennan, Vanessa Porter, Andrew Galbraith, Cameron J Grisdale, Luka Culibrk, John H Dupuis, Richard Corbett, James Hopkins, Reanne Bowlby, Pawan Pandoh, Duane E Smailus, Dean Cheng, Tina Wong, Connor Frey, Yaoqing Shen, Eleanor Lewis, Luis F Paulin, Fritz J Sedlazeck, Jessica M T Nelson, Eric Chuah, Karen L Mungall, Richard A Moore, Robin Coope, Andrew J Mungall, Melissa K Mcconechy, Laura M Williamson, Kasmintan A Schrader, Stephen Yip, Marco A Marra, Janessa Laskin, Steven J M Jones

Faculty, Staff and Students Publications

The Long-Read Personalized OncoGenomics (POG) dataset comprises a cohort of 189 patient tumors and 41 matched normal samples sequenced using the Oxford Nanopore Technologies PromethION platform. This dataset from the POG program and the Marathon of Hope Cancer Centres Network includes DNA and RNA short-read sequence data, analytics, and clinical information. We show the potential of long-read sequencing for resolving complex cancer-related structural variants, viral integrations, and extrachromosomal circular DNA. Long-range phasing facilitates the discovery of allelically differentially methylated regions (aDMRs) and allele-specific expression, including recurrent aDMRs in the cancer genes RET and CDKN2A. Germline promoter methylation in MLH1 can …

Multi-Organ Gene Expression Analysis And Network Modeling Reveal Regulatory Control Cascades During The Development Of Hypertension In Female Spontaneously Hypertensive Rat, Eden Hornung, Sirisha Achanta, Alison Moss, James S. Schwaber, Rajanikanth Vadigepalli

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Hypertension is a multifactorial disease with stage-specific gene expression changes occurring in multiple organs over time. The temporal sequence and the extent of gene regulatory network changes occurring across organs during the development of hypertension remain unresolved. In this study, female spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats were used to analyze expression patterns of 96 genes spanning inflammatory, metabolic, sympathetic, fibrotic, and renin-angiotensin (RAS) pathways in five organs, at five time points from the onset to established hypertension. We analyzed this multi-dimensional dataset containing ~15,000 data points and developed a data-driven dynamic network model that accounts for …

Large-Scale Application Of Clingen-Insight Apc-Specific Acmg/Amp Variant Classification Criteria Leads To Substantial Reduction In Vus, Xiaoyu Yin, Marcy Richardson, Andreas Laner, Xuemei Shi, Elisabet Ognedal, Valeria Vasta, Thomas V O Hansen, Marta Pineda, Deborah Ritter, Johan De Dunnen, Emadeldin Hassanin, Wencong Lyman Lin, Ester Borras, Karl Krahn, Margareta Nordling, Alexandra Martins, Khalid Mahmood, Emily Nadeau, Victoria Beshay, Carli Tops, Maurizio Genuardi, Tina Pesaran, Ian M Frayling, Gabriel Capellá, Andrew Latchford, Sean V Tavtigian, Carlo Maj, Sharon E Plon, Marc S Greenblatt, Finlay A Macrae, Isabel Spier, Stefan Aretz

Faculty, Staff and Students Publications

Pathogenic constitutional APC variants underlie familial adenomatous polyposis, the most common hereditary gastrointestinal polyposis syndrome. To improve variant classification and resolve the interpretative challenges of variants of uncertain significance (VUSs), APC-specific variant classification criteria were developed by the ClinGen-InSiGHT Hereditary Colorectal Cancer/Polyposis Variant Curation Expert Panel (VCEP) based on the criteria of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology (ACMG/AMP). A streamlined algorithm using the APC-specific criteria was developed and applied to assess all APC variants in ClinVar and the International Society for Gastrointestinal Hereditary Tumours (InSiGHT) international reference APC Leiden Open Variation …

Impact Of Pathologist-Directed Comprehensive Genomic Profiling In Advanced Non-Small-Cell Lung Cancer In A Large Healthcare System, R Meng, Carlo Bifulco, Brian Piening, See Full List Of Authors In Comments

Articles, Abstracts, and Reports

No abstract provided.

Genomic Landscape Of Fusions In Solid Tumors Detected By Dna And Rna Comprehensive Genomic Profiling At A Large Community Health System, A Dowdell, Carlo Bifulco, Brian Piening, See Full List Of Authors In Comments

Articles, Abstracts, and Reports

No abstract provided.

Protracted Maternal Malnutrition Induces Aberrant Changes In Maternal Uterine Artery Hemodynamics And The Metabolic Profiles Of The Dam And Neonate, Jennifer F. Thorson, Ligia D. Prezotto

Department of Animal Science: Faculty Publications

Malnutritional stress during gestation is a well-established driver of metabolic disfunction in offspring. Extended exposure to malnutrition requires metabolic plasticity as the animal shifts toward a catabolic state. In this paper we demonstrate the influence of malnutrition throughout gestation on uterine artery hemodynamics and the metabolism of the dam and neonate. We hypothesized that gestational malnutrition reduces blood flow of the maternal uterine artery and regulates the metabolic profile of the dam and offspring. Further, the combination of these factors consequently influences the concentration of metabolites in the cerebrospinal fluid of the neonate at birth. To test our hypotheses, pregnant …

Repeated Shifts In Sociality Are Associated With Fine-Tuning Of Highly Conserved And Lineage-Specific Enhancers In A Socially Flexible Bee, Beryl M. Jones, Andrew E. Webb, Scott M. Geib, Sheina Sim, Rena M. Schweizer, Michael G. Branstetter, Jay D. Evans, Sarah D. Kocher

Entomology Faculty Publications

Comparative genomic studies of social insects suggest that changes in gene regulation are associated with evolutionary transitions in social behavior, but the activity of predicted regulatory regions has not been tested empirically. We used self-transcribing active regulatory region sequencing, a high-throughput enhancer discovery tool, to identify and measure the activity of enhancers in the socially variable sweat bee, Lasioglossum albipes. We identified over 36,000 enhancers in the L. albipes genome from 3 social and 3 solitary populations. Many enhancers were identified in only a subset of L. albipes populations, revealing rapid divergence in regulatory regions within this species. Population-specific enhancers …

Engineering The Coherent Phonon Transport In Polar Ferromagnetic Oxide Superlattices, In Hyeok Choi, Seung Gyo Jeong, Do-Gyeom Jeong, Ambrose Seo, Woo Seok Choi, Jong Seok Lee

Chemical and Materials Engineering Faculty Publications

Artificial superlattices composed of perovskite oxides serves as an essential platform for engineering coherent phonon transport by redefining the lattice periodicity, which strongly influences the lattice-coupled phase transitions in charge and spin degrees of freedom. However, previous methods of manipulating phonons have been limited to controlling the periodicity of superlattice, rather than utilizing complex mutual interactions that are prominent in transition metal oxides. In this study on oxide superlattices composed of ferromagnetic metallic SrRuO3 and quantum paraelectric SrTiO3 , phonon modulation by controlling the geometry of superlattice in atomic-scale precision is realized, demonstrating the coherent phonon engineering using structural and …

Xenomake: A Pipeline For Processing And Sorting Xenograft Reads From Spatial Transcriptomic Experiments, Benjamin S Strope, Katherine E Pendleton, William Z Bowie, Gloria V Echeverria, Qian Zhu

Faculty, Staff and Students Publications

SUMMARY: Xenograft models are attractive models that mimic human tumor biology and permit one to perturb the tumor microenvironment and study its drug response. Spatially resolved transcriptomics (SRT) provides a powerful way to study the organization of xenograft models, but currently there is a lack of specialized pipeline for processing xenograft reads originated from SRT experiments. Xenomake is a standalone pipeline for the automated handling of spatial xenograft reads. Xenomake handles read processing, alignment, xenograft read sorting, and connects well with downstream spatial analysis packages. We additionally show that Xenomake can correctly assign organism-specific reads, reduce sparsity of data by …

Loss-Of-Function In Rbbp5 Results In A Syndromic Neurodevelopmental Disorder Associated With Microcephaly, Yue Huang, Kristy L Jay, Alden Yen-Wen Huang, Jijun Wan, Sharayu V Jangam, Odelia Chorin, Annick Rothschild, Ortal Barel, Milena Mariani, Maria Iascone, Han Xue, Undiagnosed Diseases Network, Jing Huang, Cyril Mignot, Boris Keren, Virginie Saillour, Annelise Y Mah-Som, Stephanie Sacharow, Farrah Rajabi, Carrie Costin, Shinya Yamamoto, Oguz Kanca, Hugo J Bellen, Jill A Rosenfeld, Christina G S Palmer, Stanley F Nelson, Michael F Wangler, Julian A Martinez-Agosto

Faculty, Staff and Students Publications

PURPOSE: Epigenetic dysregulation has been associated with many inherited disorders. RBBP5 (HGNC:9888) encodes a core member of the protein complex that methylates histone 3 lysine-4 and has not been implicated in human disease.

METHODS: We identify 5 unrelated individuals with de novo heterozygous variants in RBBP5. Three nonsense/frameshift and 2 missense variants were identified in probands with neurodevelopmental symptoms, including global developmental delay, intellectual disability, microcephaly, and short stature. Here, we investigate the pathogenicity of the variants through protein structural analysis and transgenic Drosophila models.

RESULTS: Both missense p.(T232I) and p.(E296D) variants affect evolutionarily conserved amino acids located at the …

Pharmacogenomic Insights In Psychiatric Care: Uncovering Novel Actionability, Allele-Specific Cyp2d6 Copy Number Variation, And Phenoconversion In 15,000 Patients, Jai N Patel, Sarah A Morris, Raul Torres, Brooke Rhead, Chris Vlangos, Daniel J Mueller, Lisa C Brown, Hailey Lefkofsky, Muneer Ali, Francisco M De La Vega, Kathleen C Barnes, Anthony Zoghbi, Joseph D Stanton, Marcus A Badgeley

Faculty, Staff and Students Publications

Pharmacogenomic testing has emerged as an aid in clinical decision making for psychiatric providers, but more data is needed regarding its utility in clinical practice and potential impact on patient care. In this cross-sectional study, we determined the real-world prevalence of pharmacogenomic actionability in patients receiving psychiatric care. Potential actionability was based on the prevalence of CYP2C19 and CYP2D6 phenotypes, including CYP2D6 allele-specific copy number variations (CNVs). Combined actionability additionally incorporated CYP2D6 phenoconversion and the novel CYP2C-TG haplotype in patients with available medication data. Across 15,000 patients receiving clinical pharmacogenomic testing, 65% had potentially actionable CYP2D6 and CYP2C19 phenotypes, and …

The Role Of Siamese In G2 Checkpoint Regulation In Arabidopsis Thaliana, Martha A. Schwall

LSU Doctoral Dissertations

Cyclin-cyclin dependent kinase (Cyclin-CDK) pairs regulate progression through the checkpoints of the cell cycle. They bind with some specificity and must be bound to for their regulative properties to be active. The presence of cyclin-CDKs is conserved throughout eukaryotes, while differences in specifics exist between yeast, animals, and plants. In Arabidopsis, SIAMESE (SIM) is a CDK inhibitor that restricts progression through mitosis. Overexpression of SIM is required for endoreplication in Arabidopsis trichomes, and overexpression of SIM results in increased endoreplication in leaf epidermal cells. SIM is expressed at high levels in the root elongation zone, where it plays a …

Dynamic Dysregulation Of Retrotransposons In Neurodegenerative Diseases At The Single-Cell Level\, Wankun Deng, Citu Citu, Andi Liu, Zhongming Zhao

Faculty, Staff and Student Publications

Retrotransposable elements (RTEs) are common mobile genetic elements comprising ∼42% of the human genome. RTEs play critical roles in gene regulation and function, but how they are specifically involved in complex diseases is largely unknown. Here, we investigate the cellular heterogeneity of RTEs using 12 single-cell transcriptome profiles covering three neurodegenerative diseases, Alzheimer's disease (AD), Parkinson's disease, and multiple sclerosis. We identify cell type marker RTEs in neurons, astrocytes, oligodendrocytes, and oligodendrocyte precursor cells that are related to these diseases. The differential expression analysis reveals the landscape of dysregulated RTE expression, especially L1s, in excitatory neurons of multiple neurodegenerative diseases. …

Adding Gastrointestinal Parasite Resistance To The Breeding Objective In Hair Sheep: Initial Step, Robert M. Forbes, Thomas W. Murphy, Joan M. Burke, David R. Notter, Matthew L. Spangler, Michael D. Macneil, Ronald M. Lewis

Department of Animal Science: Faculty Publications

The U.S. Maternal Hair Index was designed by the National Sheep Improvement Program (NSIP) to increase total weight of lamb weaned per ewe lambing (TW). Producers are interested in adding gastrointestinal nematode (GIN) resistance to this breeding objective since parasitism causes substantial economic losses. The NSIP provides producers with estimated breeding values (EBV) for postweaning fecal egg count (PFEC), an indicator of GIN resistance. Our objective was to gauge the effects of including PFEC as another selection criterion and goal trait. Selection index theory was used to construct 11 indexes. …

Identification Of Allele-Specific Kiv-2 Repeats And Impact On Lp(A) Measurements For Cardiovascular Disease Risk, Sairam Behera, Jonathan R Belyeu, Xiao Chen, Luis F Paulin, Ngoc Quynh H Nguyen, Emma Newman, Medhat Mahmoud, Vipin K Menon, Qibin Qi, Parag Joshi, Santica Marcovina, Massimiliano Rossi, Eric Roller, James Han, Vitor Onuchic, Christy L Avery, Christie M Ballantyne, Carlos J Rodriguez, Robert C Kaplan, Donna M Muzny, Ginger A Metcalf, Richard A Gibbs, Bing Yu, Eric Boerwinkle, Michael A Eberle, Fritz J Sedlazeck

Faculty, Staff and Students Publications

The abundance of Lp(a) protein holds significant implications for the risk of cardiovascular disease (CVD), which is directly impacted by the copy number (CN) of KIV-2, a 5.5 kbp sub-region. KIV-2 is highly polymorphic in the population and accurate analysis is challenging. In this study, we present the DRAGEN KIV-2 CN caller, which utilizes short reads. Data across 166 WGS show that the caller has high accuracy, compared to optical mapping and can further phase approximately 50% of the samples. We compared KIV-2 CN numbers to 24 previously postulated KIV-2 relevant SNVs, revealing that many are ineffective predictors of KIV-2 …

The Primacy Of Density-Mediated Indirect Effects In A Community Of Wolves, Elk, And Aspen, Elaine M. Brice, Eric J. Larsen, Daniel R. Stahler, Daniel R. Macnulty

Aspen Bibliography

The removal or addition of a predator in an ecosystem can trigger a trophic cascade, whereby the predator indirectly influences plants and/or abiotic processes via direct effects on its herbivore prey. A trophic cascade can operate through a density-mediated indirect effect (DMIE), where the predator reduces herbivore density via predation, and/or through a trait-mediated indirect effect (TMIE), where the predator induces an herbivore trait response that modifies the herbivore's effect on plants. Manipulative experiments suggest that TMIEs are an equivalent or more important driver of trophic cascades than are DMIEs. Whether this applies generally in nature is uncertain because few …

The Giab Genomic Stratifications Resource For Human Reference Genomes, Nathan Dwarshuis, Divya Kalra, Jennifer Mcdaniel, Philippe Sanio, Pilar Alvarez Jerez, Bharati Jadhav, Wenyu Eddy Huang, Rajarshi Mondal, Ben Busby, Nathan D Olson, Fritz J Sedlazeck, Justin Wagner, Sina Majidian, Justin M Zook

Faculty, Staff and Students Publications

Despite the growing variety of sequencing and variant-calling tools, no workflow performs equally well across the entire human genome. Understanding context-dependent performance is critical for enabling researchers, clinicians, and developers to make informed tradeoffs when selecting sequencing hardware and software. Here we describe a set of “stratifications,” which are BED files that define distinct contexts throughout the genome. We define these for GRCh37/38 as well as the new T2T-CHM13 reference, adding many new hard-to-sequence regions which are critical for understanding performance as the field progresses. Specifically, we highlight the increase in hard-to-map and GC-rich stratifications in CHM13 relative to the …

A Long-Recognized But Undescribed New Species Of Cyprinella (Cypriniformes: Leuciscidae) From North Carolina And South Carolina, United States, Bryn H. Tracy, Fred C. Rohde, Michael A. Perkins, Laura M. Lee, Kara B. Carlson, Madelyn Mccutcheon, Brena K. Jones, Heather K. Evans

Southeastern Fishes Council Proceedings

Cyprinella leptocheilus sp. nov., Siouan Thinlip Chub, is described as a new species that is endemic to Sand Hills and upper Coastal Plain streams in North Carolina and South Carolina. Recognized as an undescribed species since the early 1970s, this fish was known in the literature and in museum electronic databases as Hybopsis n. sp., H. sp. cf. zanema, Cyprinella n. sp., and C. sp. cf. zanema. Unofficially, it had gone by the common name Thinlip Chub. It was thought to be closely related to the two other barbeled Cyprinella species: Thicklip Chub, …

Electric Potential Energy Optimized 3d Radial Sampling Trajectories For Mri, Christopher Huynh, Datta Singh Goolaub, Christopher K Macgowan

Faculty, Staff and Students Publications

A novel method for creating “golden” 3D center-out radial MRI sampling trajectories was developed and analyzed. This method, called ELECTRO (ELECTRic potential energy Optimized), uses repulsive forces to minimize electric potential energy. An objective function , the electric potential energies of all subsets of consecutive readouts in a 3D radial trajectory, and its reduced form were minimized using a multi-stage optimization strategy. A metric called normalized mean nearest neighbor angular distance (NMNA) was proposed for describing distributions of points on a sphere. ELECTRO and other relevant golden trajectories were compared in silico using NMNA and point spread function analysis. Consecutive …

When Less Is More: Sketching With Minimizers In Genomics, Malick Ndiaye, Silvia Prieto-Baños, Lucy M Fitzgerald, Ali Yazdizadeh Kharrazi, Sergey Oreshkov, Christophe Dessimoz, Fritz J Sedlazeck, Natasha Glover, Sina Majidian

Faculty, Staff and Students Publications

The exponential increase in sequencing data calls for conceptual and computational advances to extract useful biological insights. One such advance, minimizers, allows for reducing the quantity of data handled while maintaining some of its key properties. We provide a basic introduction to minimizers, cover recent methodological developments, and review the diverse applications of minimizers to analyze genomic data, including de novo genome assembly, metagenomics, read alignment, read correction, and pangenomes. We also touch on alternative data sketching techniques including universal hitting sets, syncmers, or strobemers. Minimizers and their alternatives have rapidly become indispensable tools for handling vast amounts of data.

Effects Of Cadherin Mediated Contact Normalization On Oncogenic Src Kinase Mediated Gene Expression And Protein Phosphorylation, Rachel E Nicoletto, Cayla J Holdcraft, Ariel C Yin, Edward P Retzbach, Stephanie A Sheehan, Amanda A Greenspan, Christopher M Laugier, Jason Trama, Caifeng Zhao, Haiyan Zheng, Gary S Goldberg

Rowan-Virtua School of Osteopathic Medicine Departmental Research

Nontransformed cells form heterotypic cadherin junctions with adjacent transformed cells to inhibit tumor cell growth and motility. Transformed cells must override this form of growth control, called "contact normalization", to invade and metastasize during cancer progression. Heterocellular cadherin junctions between transformed and nontransformed cells are needed for this process. However, specific mechanisms downstream of cadherin signaling have not been clearly elucidated. Here, we utilized a β-catenin reporter construct to determine if contact normalization affects Wnt signaling in transformed cells. β-catenin driven GFP expression in Src transformed mouse embryonic cells was decreased when cultured with cadherin competent nontransformed cells compared to …

Stratomod: Predicting Sequencing And Variant Calling Errors With Interpretable Machine Learning, Nathan Dwarshuis, Peter Tonner, Nathan D Olson, Fritz J Sedlazeck, Justin Wagner, Justin M Zook

Faculty, Staff and Students Publications

Despite the variety in sequencing platforms, mappers, and variant callers, no single pipeline is optimal across the entire human genome. Therefore, developers, clinicians, and researchers need to make tradeoffs when designing pipelines for their application. Currently, assessing such tradeoffs relies on intuition about how a certain pipeline will perform in a given genomic context. We present StratoMod, which addresses this problem using an interpretable machine-learning classifier to predict germline variant calling errors in a data-driven manner. We show StratoMod can precisely predict recall using Hifi or Illumina and leverage StratoMod's interpretability to measure contributions from difficult-to-map and homopolymer regions for …

Mates: A Deep Learning-Based Model For Locus-Specific Quantification Of Transposable Elements In Single Cell, Ruohan Wang, Yumin Zheng, Zijian Zhang, Kailu Song, Erxi Wu, Xiaopeng Zhu, Tao P Wu, Jun Ding

Faculty, Staff and Students Publications

Transposable elements (TEs) are crucial for genetic diversity and gene regulation. Current single-cell quantification methods often align multi-mapping reads to either 'best-mapped' or 'random-mapped' locations and categorize them at the subfamily levels, overlooking the biological necessity for accurate, locus-specific TE quantification. Moreover, these existing methods are primarily designed for and focused on transcriptomics data, which restricts their adaptability to single-cell data of other modalities. To address these challenges, here we introduce MATES, a deep-learning approach that accurately allocates multi-mapping reads to specific loci of TEs, utilizing context from adjacent read alignments flanking the TE locus. When applied to diverse single-cell …

Larp1 Haploinsufficiency Is Associated With An Autosomal Dominant Neurodevelopmental Disorder, James Chettle, Raymond J Louie, Olivia Larner, Robert Best, Kevin Chen, Josephine Morris, Zinaida Dedeic, Anna Childers, R Curtis Rogers, Barbara R Dupont, Cindy Skinner, Sébastien Küry, Kevin Uguen, Marc Planes, Danielle Monteil, Megan Li, Aviva Eliyahu, Lior Greenbaum, Nofar Mor, Thomas Besnard, Bertrand Isidor, Benjamin Cogné, Alyssa Blesson, Anne Comi, Ingrid M Wentzensen, Blake Vuocolo, Seema R Lalani, Roberta Sierra, Lori Berry, Kent Carter, Stephan J Sanders, Sarah P Blagden

Faculty, Staff and Students Publications

Autism spectrum disorder (ASD) is a neurodevelopmental disorder (NDD) that affects approximately 4% of males and 1% of females in the United States. While causes of ASD are multi-factorial, single rare genetic variants contribute to around 20% of cases. Here, we report a case series of seven unrelated probands (6 males, 1 female) with ASD or another variable NDD phenotype attributed to de novo heterozygous loss of function or missense variants in the gene LARP1 (La ribonucleoprotein 1). LARP1 encodes an RNA-binding protein that post-transcriptionally regulates the stability and translation of thousands of mRNAs, including those regulating cellular metabolism and …

Single-Cell Somatic Copy Number Variants In Brain Using Different Amplification Methods And Reference Genomes, Ester Kalef-Ezra, Zeliha Gozde Turan, Diego Perez-Rodriguez, Ida Bomann, Sairam Behera, Caoimhe Morley, Sonja W Scholz, Zane Jaunmuktane, Jonas Demeulemeester, Fritz J Sedlazeck, Christos Proukakis

Faculty, Staff and Students Publications

The presence of somatic mutations, including copy number variants (CNVs), in the brain is well recognized. Comprehensive study requires single-cell whole genome amplification, with several methods available, prior to sequencing. Here we compare PicoPLEX with two recent adaptations of multiple displacement amplification (MDA): primary template-directed amplification (PTA) and droplet MDA, across 93 human brain cortical nuclei. We demonstrate different properties for each, with PTA providing the broadest amplification, PicoPLEX the most even, and distinct chimeric profiles. Furthermore, we perform CNV calling on two brains with multiple system atrophy and one control brain using different reference genomes. We find that 20.6% …

Unravelling The Impact Of Blood Metabolites, And Lifestyle Factors On Periodontal Disease Using Mendelian Randomization, Rhea Charles

USF Tampa Graduate Theses and Dissertations

Periodontal disease remains a global public health concern. Despite the availability of preventive and therapeutic strategies, the multifactorial nature of periodontitis complicates its understanding and management. Periodontal disease is associated with an increased risk of chronic conditions, including ischemic heart disease (IHD), gestational hypertension, respiratory diseases such as COPD and bronchitis, and various cancers, including kidney and pancreatic cancers. Moreover, individuals with diabetes, autoimmune diseases like lupus and Crohn’s disease, and osteoporosis are more likely to develop periodontitis. The ambiguity in the direction of causality between periodontal disease and its associated conditions poses challenges for effective treatment. Mendelian randomization offers …