Genetics and Genomics Commons^™

Scalable Nanopore Sequencing Of Human Genomes Provides A Comprehensive View Of Haplotype-Resolved Variation And Methylation, Mikhail Kolmogorov, Kimberley J Billingsley, Mira Mastoras, Melissa Meredith, Jean Monlong, Ryan Lorig-Roach, Mobin Asri, Pilar Alvarez Jerez, Laksh Malik, Ramita Dewan, Xylena Reed, Rylee M Genner, Kensuke Daida, Sairam Behera, Kishwar Shafin, Trevor Pesout, Jeshuwin Prabakaran, Paolo Carnevali, Jianzhi Yang, Arang Rhie, Sonja W Scholz, Bryan J Traynor, Karen H Miga, Miten Jain, Winston Timp, Adam M Phillippy, Mark Chaisson, Fritz J Sedlazeck, Cornelis Blauwendraat, Benedict Paten

Faculty, Staff and Students Publications

Long-read sequencing technologies substantially overcome the limitations of short-reads but have not been considered as a feasible replacement for population-scale projects, being a combination of too expensive, not scalable enough or too error-prone. Here we develop an efficient and scalable wet lab and computational protocol, Napu, for Oxford Nanopore Technologies long-read sequencing that seeks to address those limitations. We applied our protocol to cell lines and brain tissue samples as part of a pilot project for the National Institutes of Health Center for Alzheimer's and Related Dementias. Using a single PromethION flow cell, we can detect single nucleotide polymorphisms with …

Views Of Adolescents And Young Adults With Cancer And Their Oncologists Toward Patients' Participation In Genomic Research, Amanda M Gutierrez, Jill O Robinson, Robin Raesz-Martinez, Isabel Canfield, Mary A Majumder, Sarah Scollon, Lauren R Desrosiers, Rebecca L Hsu, Wendy Allen-Rhoades, D Williams Parsons, Sharon E Plon, Amy L Mcguire, Janet Malek

Faculty, Staff and Students Publications

Purpose:

With increased use of genomic testing in cancer research and clinical care, it is important to understand the perspectives and decision-making preferences of adolescents and young adults (AYAs) with cancer and their treating oncologists.

Methods:

We conducted an interview substudy of the BASIC3 Study, which enrolled newly diagnosed cancer patients <18 years of age with assent. Of 32 young adults (YAs) with cancer who reached the age of majority (AOM; 18 years) while on study, 12 were successfully approached and all consented to study continuation at AOM. Of those, seven completed an interview. Patients' oncologists, who enrolled and participated in return of clinical genomic results, were also interviewed (n = 12). Interviews were transcribed, deidentified, and analyzed using thematic analysis.

Results:

YAs cited the possibility of helping others and advancing science as major reasons for their assent to initial study enrollment and their willingness to consent at AOM. YAs thought obtaining informed consent from research participants for …

Current Perspectives On Mass Spectrometry-Based Immunopeptidomics: The Computational Angle To Tumor Antigen Discovery, Bing Zhang, Michal Bassani-Sternberg

Faculty, Staff and Students Publications

Identification of tumor antigens presented by the human leucocyte antigen (HLA) molecules is essential for the design of effective and safe cancer immunotherapies that rely on T cell recognition and killing of tumor cells. Mass spectrometry (MS)-based immunopeptidomics enables high-throughput, direct identification of HLA-bound peptides from a variety of cell lines, tumor tissues, and healthy tissues. It involves immunoaffinity purification of HLA complexes followed by MS profiling of the extracted peptides using data-dependent acquisition, data-independent acquisition, or targeted approaches. By incorporating DNA, RNA, and ribosome sequencing data into immunopeptidomics data analysis, the proteogenomic approach provides a powerful means for identifying …

Prevalence Of Pathogenic Germline Variants In Adult-Type Diffuse Glioma, Malcolm F Mcdonald, Lyndsey L Prather, Cassandra R Helfer, Ethan B Ludmir, Alfredo E Echeverria, Shlomit Yust-Katz, Akash J Patel, Benjamin Deneen, Ganesh Rao, Ali Jalali, Shweta U Dhar, Chris I Amos, Jacob J Mandel

Faculty, Staff and Students Publications

BACKGROUND: No consensus germline testing guidelines currently exist for glioma patients, so the prevalence of germline pathogenic variants remains unknown. This study aims to determine the prevalence and type of pathogenic germline variants in adult glioma.

METHODS: A retrospective review at a single institution with paired tumor/normal sequencing from August 2018-April 2022 was performed and corresponding clinical data were collected.

RESULTS: We identified 152 glioma patients of which 15 (9.8%) had pathogenic germline variants. Pathogenic germline variants were seen in 11/84 (13.1%) of Glioblastoma, IDH wild type; 3/42 (7.1%) of Astrocytoma, IDH mutant; and 1/26 (3.8%) of Oligodendroglioma, IDH mutant, …

Neurodevelopmental Deficits And Cell-Type-Specific Transcriptomic Perturbations In A Mouse Model Of Hnrnpu Haploinsufficiency, Sarah A Dugger, Ryan S Dhindsa, Gabriela De Almeida Sampaio, Andrew K Ressler, Elizabeth E Rafikian, Sabrina Petri, Verity A Letts, Jiajie Teoh, Junqiang Ye, Sophie Colombo, Yueqing Peng, Mu Yang, Michael J Boland, Wayne N Frankel, David B Goldstein

Faculty, Staff and Students Publications

Heterozygous de novo loss-of-function mutations in the gene expression regulator HNRNPU cause an early-onset developmental and epileptic encephalopathy. To gain insight into pathological mechanisms and lay the potential groundwork for developing targeted therapies, we characterized the neurophysiologic and cell-type-specific transcriptomic consequences of a mouse model of HNRNPU haploinsufficiency. Heterozygous mutants demonstrated global developmental delay, impaired ultrasonic vocalizations, cognitive dysfunction and increased seizure susceptibility, thus modeling aspects of the human disease. Single-cell RNA-sequencing of hippocampal and neocortical cells revealed widespread, yet modest, dysregulation of gene expression across mutant neuronal subtypes. We observed an increased burden of differentially-expressed genes in mutant excitatory …

Tox3 Rs3803662 Polymorphism Is Associated With Breast Cancer Protection In Northeastern Mexican Woman, Orlando D. Solis-Coronado, Hazyadee F. Rodríguez-Gutiérrez, Monica P. Villarreal-Vela, Ricardo M. Cerda-Flores, Juan F. González-Guerrero, Oscar Vidal-Gutiérrez, Diana C. Pérez-Ibave, Maria Lourdes Garza-Rodríguez

Research Symposium

Introduction: Low penetrance genes are involved in breast cancer (BC) and confer risk for the development of this neoplasia. Different single nucleotide polymorphisms (SNPs) associated with BC have been identified, such as rs3803662 (TOX3), which is related to estrogen receptors in European and African-American women. The contribution of this variant in the Mexican population is unknown. The objective of this study was to evaluate, through a case-control design, the association of the SNP rs3803662 (TOX3), with the risk of BC in women from northeastern Mexico.

Methods: We included 434 cases and 228 controls. Genotyping was carried out using RFLPs. The …

South Coast Offshore Crustacean Resource Of Western Australia Harvest Strategy, Department Of Primary Industries And Regional Development, Western Australia

Fisheries Management Papers

Harvest strategies for aquatic resources in Western Australia (WA) that are managed by the Department of Primary Industries and Regional Development (DPIRD, the Department) are formal documents that ensures decision-making processes are consistent with the principles of Ecologically Sustainable Development (ESD; Fletcher 2002) and Ecosystem Based Fisheries Management (EBFM; Fletcher et al. 2012). The objectives of ESD are reflected in the objects of the Fish Resources Management Act 1994 (FRMA) and the Aquatic Resources Management Act 2016 (ARMA), which is anticipated replace the FRMA once enacted. At this point, the Fish Resources Management Regulations 1995 (FRMR) is also anticipated to …

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.

Existing Evidence For Influenza B Virus Adaptations To Drive Replication In Humans As The Primary Host, Matthew J. Pekarek, Eric A. Weaver

Nebraska Center for Virology: Faculty Publications

Influenza B virus (IBV) is one of the two major types of influenza viruses that circulate each year. Unlike influenza A viruses, IBV does not harbor pandemic potential due to its lack of historical circulation in non-human hosts. Many studies and reviews have highlighted important factors for host determination of influenza A viruses. However, much less is known about the factors driving IBV replication in humans. We hypothesize that similar factors influence the host restriction of IBV. Here, we compile and review the current understanding of host factors crucial for the various stages of the IBV viral replication cycle. While …

Trimeric Complex Interactions Of Antp-Tbp With Tfiieb And Exd Are Involved In The Genetic Control Of Drosophila Melanogaster, Gustavo Jiménez Mejía, Ruben De Jesus Montalvo Mendez, Claudia Dalila Altamirano Torres, Diana Reséndez Pérez

Research Symposium

Background: Homeoproteins are transcriptional factors (TFs) that shape animal body axes during development. These TFs are highly conserved and represent one of the most fascinating groups of regulatory molecules. Reports shown the multiplicity of interactions in hox proteins, as complexes trimeric involved to transcriptional activity. The study of trimeric complexes in Hox interactome will allow the better understanding of Hox genetic regulation during embryonic development.

Methodology: Using a new combination BiFCFRET approach performed in HEK293, the quantification was performed by FRETTY of ImageJ. Fly crosses were incubated at 25ºC on standard yeast-agar-cornmeal medium. Embryo cuticle preparations were carried out according …

Multiple Rsv Strains Infecting Hep-2 And A549 Cells Reveal Cell Line-Dependent Differences In Resistance To Rsv Infection, Anubama Rajan, Felipe-Andres Piedra, Letisha Aideyan, Trevor Mcbride, Matthew Robertson, Hannah L. Johnson, Gina Marie Aloisio, David Henke, Cristian Coarfa, Fabio Stossi, Vipin Kumar Menon, Harshavardhan Doddapaneni, Donna Marie Muzny, Sara Joan Javornik Cregeen, Kristi Louise Hoffman, Joseph Petrosino, Richard A. Gibbs, Vasanthi Avadhanula, Pedro A. Piedra

Research Symposium

Background: Respiratory syncytial virus (RSV) is the major viral driver of a global pediatric respiratory disease burden disproportionately borne by the poor¹. Thus, RSV, like SARS-CoV-2, combines with congenital and environmental and host-history-dependent factors to create a spectrum of disease with greatest severity most frequently occurring in those least able to procure treatment.

Methods: Here we apply whole genome sequencing and a suite of other molecular biological techniques to survey host-virus dynamics in infections of two distinct cell lines (HEp2 and A549) with four strains representative of known RSV genetic diversity.

Results: We observed non-gradient patterns of RSV …

Human Ipsc Derived Cardiomyocyte Model Reveals The Transcriptomic Bases Of Covid-19 Associated Myocardial Injury, Kashish Kumar, Satish Kumar, Erica De Leon, Joanne E. Curran, Sarah Williams-Blangero, John Blangero

Research Symposium

Background: Multi-organ complications have been the hallmark of severe COVID-19; cardiac injuries were reported in 20% to 30% of hospitalized COVID-19 patients, although the disease etiology remains poorly understood. This study leveraged genome-wide RNA-sequence data generated using induced pluripotent stem cell (iPSC) differentiated cardiomyocytes (CMs) and in vitro modeling of SARS-CoV-2 infection in CMs, to understand the molecular mechanisms of COVID-19 myocardial injuries for novel diagnostic and therapeutic development.

Methods: Raw RNA-sequence data sets, GSE165242 and GSE150392 were aligned to human genome assembly GRCh38 and gene expressions were quantified. Differentially expressed (DE) genes between experimental groups were identified using moderated …

Gene-By-Environment Expression And Calculation Of The Frailty Index, Eron G. Manuosv, Vincent P. Diego, John Blangero, Michael C. Mahaney, Sarah Williams-Blangero

Research Symposium

Background: Frailty can be described as a phenotype (e.g., sarcopenia, reduced grip strength, decreased VO2 max) or as a ratio of deficits, i.e., a Frailty Index (FI). FI predicts survival, death, cognitive impairment, falls, and hospitalizations. Frailty is influenced by both genes and environment. We calculated the FI as the sum of measured deficits divided by the total number of items assessed in a pedigree-based sample of 1,029 Mexican Americans participants in the San Antonio Family Heart Study. We performed a novel search for genotype-by-environment interactions (GXE) influencing FI. Such interactions lead to heritable differences between individuals in their responses …

Whole Genome Sequence Data Implicate Rbfox1 In Epilepsy Risk In Baboons, Mark Z. Kos, Melanie A. Carless, Lucy Blondell, Mary M. Leland, Koyle D. Knape, Harald H. H. Goring, Charles A. Szabo

Research Symposium

Background: Baboons exhibit a genetic generalized epilepsy (GGE) that resembles juvenile myoclonic epilepsy and may represent a suitable genetic model for human epilepsy. The genetic underpinnings of epilepsy were investigated in a baboon colony at the Southwest National Primate Research Center (San Antonio, TX) through the analysis of whole-genome sequence (WGS) data.

Methods: Baboon WGS data were obtained for 38 cases and 19 healthy controls from the NCBI Sequence Read Archive and, after standard QC filtering, two subsets of variants were examined: (1) 20,881 SNPs from baboon homologs of 19 candidate GGE genes; and (2) 36,169 protein-altering SNPs. Association tests …

Antp Transcriptional Activity Is Modulated By The Formation Of The Trimeric Antp-Tbp Complexes With Tfiieβ, Exd And Bip2, Norma C. Hernández Bautista, Gustavo Jiménez Mejía, Claudia Altamirano Torres, Diana Reséndez Pérez

Research Symposium

Homeoproteins are transcriptional factors that bind to DNA through a highly conserved binding domain known as the homeodomain (HD) which recognizes short regions rich in AT to control the development of the body appendages of organisms. However, their structural and recognition similarities make it difficult to explain how homeoproteins are capable of carrying out their function. Previous results have shown that Antp homeoprotein can establish dimeric interactions with TBP, TFIIEβ, Exd, BIP2 and more recently through BiFC-FRET we confirmed that Antp and TBP can form trimeric complexes with TFIIEβ/Exd/BIP2. Therefore, is important to show how these trimeric complexes modulate Antp …

Tata-Box Binding Protein Interacts With Antp, Scr, Ubx And Abdb Through Their N-Terminal Domains, Rubén Montalvo Méndez, Gustavo Jiménez Mejía, Diana Reséndez Pérez

Research Symposium

Background: Hox proteins are transcriptional factors (TFs) that define segment identity during embryonic development regulating specific target genes. These TFs interact with cofactors for DNA specificity and other TFs to regulate gene expression, which include basal transcriptional machinery members like BIP2, Med19, TFIIEβ, M1BP and TBP. Since TBP glutamine homopeptide (PolyQ) act as an interaction domain involved transcriptional regulation, we analyzed if TBP interact with Antp, Scr, Ubx and AbdB through its PolyQ region.

Methods: We used Bimolecular Fluorescent Complementation (BiFC) to determine TBP interaction with Antp, Scr, Ubx and AbdB as well as the implication of their homeodomain (HD) …

Microrna-34a And Long Non-Coding Rna Malat1 Is Associated With Hpv Status And Viral Load In Premalignant Cervical Lesions, Orlando Solis-Coronado, Juan A. García-Quiñones, Mariel Aracely Oyervides-Muñoz, Victor Treviño, Celia N. Sanchez-Dominguez, Antonio A. Pérez-Maya, Diana Cristina Perez-Ibave, Oscar Vidal-Gutierrez, Juan Francisco González-Guerero, Genaro A. Ramírez-Correa, María Lourdes Garza-Rodríguez

Research Symposium

Background: Cervical cancer (CC) is one of the most common gynecological malignancies in the world, and human papillomavirus (HPV) infection is the most important risk factor for their development. Although there are methods for the early detection of CC and HPV infection, but there are not highly sensitive and specific, for it´s necessary to investigate alternatives such as miR-34a and MALAT1, implicated in the pathogenesis of CC. The objective was to evaluate the association of HPV status, viral load, the presence of coinfections, and the grade of CC precursor lesions with miR-34a and MALAT1 expression in patients with high …

Determination Of Hfe C282y Mutation And Its Association With The Iron Status And Viral Load In Hiv Patients From Reynosa, Tamaulipas, Juan Carlos Hernández, Marisol Rosas Díaz, Esperanza Milagros García Oropesa, Santos Graciela Montemayor Beltrán, Juana Díaz García, Imelda Ramírez Puente

Research Symposium

Background: The HFE protein has a fundamental role in iron homeostasis, the HFE C282Y mutation prevents the specific function of the protein, causing greater intestinal absorption of iron and intracellular accumulation. The HIV virus causes a disease that attacks the cells of the immune system, mainly CD 4 T lymphocytes inducing their destruction and immunosuppression of the patient. Some viruses have the ability to disrupt cellular metabolic processes during their own replication, such is the case of HIV-1, which is involved in alteration of iron metabolism resulting in an overload of iron.

Methods: An exploratory, descriptive, cross-sectional and prolective study …

Genomic And Transcriptomic Analyses Reveal Polygenic Architecture For Ecologically Important Traits In Aspen (Populus Tremuloides Michx.), Jennifer F. L. Riehl, Christopher T. Cole, Clay J. Marrow, Hilary L. Barker, Carolina Bernhardsson, Kennedy Rubert-Nason, Pär K. Ingvarsson, Richard L. Lindroth

Aspen Bibliography

Intraspecific genetic variations in foundation species such as aspen (Populus tremuloides Michx.) shapes their impact on forest structure and function. Identifying genes underlying ecologically important traits is key to understanding that impact. Previous studies, using single-locus genome-wide association (GWA) analyses to identify candidate genes, have identified fewer genes than anticipated for highly heritable quantitative traits. Mounting evidence suggests that polygenic control of quantitative traits is largely responsible for this "missing heritability" phenomenon. Our research characterized the genetic architecture of 30 ecologically important traits using a common garden of aspect through genomic and transcriptomic analyses. A multilocus association model revealed …

Lack Of Methylation Changes In Gjb2 And Rb1 Non-Coding Regions Of Cochlear Implant Patients With Sensorineural Hearing Loss, Angelo Augusto M Sumalde, Ivana V Yang, Talitha Karisse L Yarza, Celina Ann M Tobias-Grasso, Ma Leah C Tantoco, Elizabeth Davidson, Abner L Chan, Mahshid S Azamian, Teresa Luisa G Cruz, Seema R Lalani, Maria Rina T Reyes-Quintos, Eva Maria Cutiongco-De La Paz, Regie Lyn P Santos-Cortez, Charlotte M Chiong

Faculty, Staff and Students Publications

OBJECTIVE: Recent advances in epigenetic studies continue to reveal novel mechanisms of gene regulation and control, however little is known on the role of epigenetics in sensorineural hearing loss (SNHL) in humans. We aimed to investigate the methylation patterns of two regions, one in

METHODS: We investigated an RB1 promoter region that was previously identified as differentially methylated in children with SNHL and lead exposure. Additionally, we investigated a sequence in an enhancer-like region within GJB2 that contains four CpGs in close proximity. Bisulfite conversion was performed on salivary DNA samples from 15 children with SNHL and 45 unrelated ethnically-matched …

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: …

Challenges In Genetic Counseling In Hereditary Cancer Syndromes In A Mexican Oncologic Center, Diana Cristina Perez-Ibave, Diana Cristina De Lourdes Perez Ibave, María Fernanda Noriega-Iriondo, Omar Alejandro Zayas-Villanueva, Fernando Alcorta-Nuñez, Juan Francisco González-Guerrero, Adelina Alcorta-Garza, David Hernandez-Barajas, Oscar Vidal-Gutierrez, Carlos Horacio Burciaga-Flores

Research Symposium

Background: In Mexico, hereditary cancer is underdiagnosed, medical geneticists give genetic counseling, but the access is limited due to the socio-economic characteristics of the population. The CUCC (Centro Universitario Contra el Cáncer) Early Cancer Detection Clinic (CECIL) created a model in which patients without cancer are enrolled in a prevention cancer screening program.

Methods: From 2016 to 2021, 3014 patients were enrolled in the prevention program. Patients were evaluated with a hereditary cancer risk survey before a consultation. Those with at least one familial hereditary risk positive answer were assessed in a consultation. We also included patients with cancer diagnoses …

Repurposing Normal Chromosomal Microarray Data To Harbor Genetic Insights Into Congenital Heart Disease, Nephi Walton, Hoang Nguyen, Sara Procknow, Darren Johnson, Alexander Anzelmi, Patrick Jay

Department of Medicine Faculty Papers

About 15% of congenital heart disease (CHD) patients have a known pathogenic copy number variant. The majority of their chromosomal microarray (CMA) tests are deemed normal. Diagnostic interpretation typically ignores microdeletions smaller than 100 kb. We hypothesized that unreported microdeletions are enriched for CHD genes. We analyzed "normal" CMAs of 1762 patients who were evaluated at a pediatric referral center, of which 319 (18%) had CHD. Using CMAs from monozygotic twins or replicates from the same individual, we established a size threshold based on probe count for the reproducible detection of small microdeletions. Genes in the microdeletions were sequentially filtered …

In Vivo Crispr/Cas9 Screening Identifies Pbrm1 As A Regulator Of Myeloid Leukemia Development In Mice, Bin E Li, Grace Y Li, Wenqing Cai, Qian Zhu, Davide Seruggia, Yuko Fujiwara, Christopher R Vakoc, Stuart H Orkin

Faculty, Staff and Students Publications

CRISPR/Cas9 screening approaches are powerful tool for identifying in vivo cancer dependencies. Hematopoietic malignancies are genetically complex disorders in which the sequential acquisition of somatic mutations generates clonal diversity. Over time, additional cooperating mutations may drive disease progression. Using an in vivo pooled gene editing screen of epigenetic factors in primary murine hematopoietic stem and progenitor cells (HSPCs), we sought to uncover unrecognized genes that contribute to leukemia progression. We, first, modeled myeloid leukemia in mice by functionally abrogating both Tet2 and Tet3 in HSPCs, followed by transplantation. We, then, performed pooled CRISPR/Cas9 editing of genes encoding epigenetic factors and …

Rna World And The Development Of Rna Protocells, Benjamin C. Mayfield

PANDION: The Osprey Journal of Research and Ideas

Origins of life research, also known as pre-biotic chemistry or astrobiology, aims to unravel the mystery of the first cell’s origin on Earth. This interdisciplinary field encompasses biology, chemistry, and physics, with the primary goal of understanding the conditions necessary for life to emerge from abiotic environments. The RNA world hypothesis suggests that early life initially used RNA instead of DNA to store genomic information and for enzymatic functions. Protocells, membrane-bound entities with metabolic processes and self-replication capabilities, likely preceded the emergence of true cells. The challenges associated with RNA world is currently an active field of research. Advancements in …

The Localization Of Centromere Protein A Is Conserved Among Tissues, Eleonora Cappelletti, Francesca M. Piras, Lorenzo Sola, Marco Santagostino, Jessica L. Petersen, Rebecca R. Bellone, Carrie J. Finno, Sichong Peng, Ted S. Kalbfleisch, Ernest Bailey, Solomon G. Nergadze, Elena Giulotto

Department of Animal Science: Faculty Publications

Centromeres are epigenetically specified by the histone H3 variant CENP-A. Although mammalian centromeres are typically associated with satellite DNA, we previously demonstrated that the centromere of horse chromosome 11 (ECA11) is completely devoid of satellite DNA. We also showed that the localization of its CENP-A binding domain is not fixed but slides within an about 500 kb region in different individuals, giving rise to positional alleles. These epialleles are inherited as Mendelian traits but their position can move in one generation. It is still unknown whether centromere sliding occurs during meiosis or during development. Here, we first improve the sequence …

A Proteogenomics Data-Driven Knowledge Base Of Human Cancer, Yuxing Liao, Sara R Savage, Yongchao Dou, Zhiao Shi, Xinpei Yi, Wen Jiang, Jonathan T Lei, Bing Zhang

Faculty, Staff and Students Publications

By combining mass-spectrometry-based proteomics and phosphoproteomics with genomics, epi-genomics, and transcriptomics, proteogenomics provides comprehensive molecular characterization of cancer. Using this approach, the Clinical Proteomic Tumor Analysis Consortium (CPTAC) has characterized over 1,000 primary tumors spanning 10 cancer types, many with matched normal tissues. Here, we present LinkedOmicsKB, a proteogenomics data-driven knowledge base that makes consistently processed and systematically precomputed CPTAC pan-cancer proteogenomics data available to the public through ∼40,000 gene-, protein-, mutation-, and phenotype-centric web pages. Visualization techniques facilitate efficient exploration and reasoning of complex, interconnected data. Using three case studies, we illustrate the practical utility of LinkedOmicsKB in providing …

Allostatic Load Index Effectively Measures Chronic Stress Status In Zoo-Housed Giraffes, Haley N. Beer, Lisa K. Karr, Trenton C. Schrader, Dustin T. Yates

Department of Animal Science: Faculty Publications

For giraffes, few standardized methods exist for quantifying chronic stress. Allostatic load index is quantified from a panel of multi-system stress biomarkers to estimate cumulative stress. Our objective was to determine whether a panel of biomarkers selected for their role in allostatic load would reflect the number of documented stress events experienced by giraffes. Cortisol, DHEA-S, cholesterol, non-esterified fatty acids (NEFA), and fructosamine were determined in serum samples from zoo-housed giraffes (n = 18). These were correlated with the overall number and frequency of ZIMS-documented stress events experienced prior to blood collection. We also compared giraffes grouped by high vs. …

Sepepquant Enhances The Detection Of Possible Isoform Regulations In Shotgun Proteomics, Yongchao Dou, Yuejia Liu, Xinpei Yi, Lindsey K Olsen, Hongwen Zhu, Qiang Gao, Hu Zhou, Bing Zhang

Faculty, Staff and Students Publications

Shotgun proteomics is essential for protein identification and quantification in biomedical research, but protein isoform characterization is challenging due to the extensive number of peptides shared across proteins, hindering our understanding of protein isoform regulation and their roles in normal and disease biology. We systematically assess the challenge and opportunities of shotgun proteomics-based protein isoform characterization using in silico and experimental data, and then present SEPepQuant, a graph theory-based approach to maximize isoform characterization. Using published data from one induced pluripotent stem cell study and two human hepatocellular carcinoma studies, we demonstrate the ability of SEPepQuant in addressing the key …

A Multicenter Analysis Of Abnormal Chromosomal Microarray Findings In Congenital Heart Disease, Benjamin J Landis, Lindsey R Helvaty, Gabrielle C Geddes, Jiuann-Huey Ivy Lin, Svetlana A Yatsenko, Cecilia W Lo, William L Border, Stephanie Burns Wechsler, Chaya N Murali, Mahshid S Azamian, Seema R Lalani, Robert B Hinton, Vidu Garg, Kim L Mcbride, Jennelle C Hodge, Stephanie M Ware

Faculty, Staff and Students Publications

Background

Chromosomal microarray analysis (CMA) provides an opportunity to understand genetic causes of congenital heart disease (CHD). The methods for describing cardiac phenotypes in patients with CMA abnormalities have been inconsistent, which may complicate clinical interpretation of abnormal testing results and hinder a more complete understanding of genotype–phenotype relationships.

Methods and Results

Patients with CHD and abnormal clinical CMA were accrued from 9 pediatric cardiac centers. Highly detailed cardiac phenotypes were systematically classified and analyzed for their association with CMA abnormality. Hierarchical classification of each patient into 1 CHD category facilitated broad analyses. Inclusive classification allowing multiple CHD types per …