Use of nCounter mRNA Profiling to Identify at-arrival Gene Expression Patterns for Predicting Bovine Respiratory Disease in Beef Cattle

2021 ◽  
Author(s):  
Matthew Scott ◽  
Amelia Woolums ◽  
Cyprianna Swiderski ◽  
Alexis Thompson ◽  
Andy Perkins ◽  
...  
Keyword(s):  
Gene Expression ◽  
Decision Tree ◽  
Beef Cattle ◽  
Respiratory Disease ◽  
Type I Interferon ◽  
Expression Patterns ◽  
Bovine Respiratory Disease ◽  
Type I ◽  
Complement Factor ◽  
Advanced Analysis

Abstract BackgroundTranscriptomics has identified at-arrival differentially expressed genes associated with bovine respiratory disease (BRD) development; however, their use as prediction molecules necessitates further evaluation. Therefore, we aimed to selectively analyze and corroborate at-arrival mRNA expression from multiple independent populations of beef cattle. In a nested case-control study, we evaluated the expression of 56 mRNA molecules from at-arrival blood samples of 234 cattle across seven populations via NanoString nCounter gene expression profiling. Analysis of mRNA was performed with nSolver Advanced Analysis software (p<0.05), comparing cattle groups based on the diagnosis of clinical BRD within 28 days of facility arrival (n=115 Healthy; n=119 BRD); BRD was further stratified for severity based on frequency of treatment and/or mortality (Treated_1, n=89; Treated_2+, n=30). Gene expression homogeneity of variance, receiver operator characteristic (ROC) curve, and decision tree analyses were performed between severity cohorts.ResultsIncreased expression of mRNAs involved in specialized pro-resolving mediator synthesis (ALOX15, HPGD), leukocyte differentiation (LOC100297044, GCSAML, KLF17), and antimicrobial peptide production (CATHL3, GZMB, LTF) were identified in Healthy cattle. BRD cattle possessed increased expression of CFB, and mRNA related to granulocytic processes (DSG1, LRG1, MCF2L) and type-I interferon activity (HERC6, IFI6, ISG15, MX1). Healthy and Treated_1 cattle were similar in terms of gene expression, while Treated_2+ cattle were the most distinct. ROC cutoffs were used to generate an at-arrival treatment decision tree, which classified 90% of Treated_2+ individuals. ConclusionsIncreased expression of complement factor B, pro-inflammatory, and type I interferon-associated mRNA hallmark the at-arrival expression patterns of cattle that develop severe clinical BRD. Here, we corroborate at-arrival mRNA markers identified in previous transcriptome studies and generate a prediction model to be evaluated in future studies. Further research is necessary to evaluate these expression patterns in a prospective manner.

scholarly journals Comprehensive at-arrival transcriptomic analysis of post-weaned beef cattle uncovers type I interferon and antiviral mechanisms associated with bovine respiratory disease mortality

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0250758
Author(s):  
Matthew A. Scott ◽  
Amelia R. Woolums ◽  
Cyprianna E. Swiderski ◽  
Andy D. Perkins ◽  
Bindu Nanduri ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Respiratory Disease ◽  
Type I Interferon ◽  
Bovine Respiratory Disease ◽  
Transcriptomic Analysis ◽  
Type I ◽  
Antiviral Defense ◽  
High Quality Research ◽  
Immunological Mechanisms ◽  
Unmapped Reads

Background Despite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Establishing a clinical diagnosis often relies upon visual detection of non-specific signs, leading to low diagnostic accuracy. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments. Results 69 DEGs (FDR<0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies. Conclusion This study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality.

scholarly journals Comprehensive at-arrival transcriptomic analysis of post-weaned beef cattle uncovers type I interferon and antiviral mechanisms associated with bovine respiratory disease mortality

2020 ◽  
Author(s):  
Matthew A. Scott ◽  
Amelia R. Woolums ◽  
Cyprianna E. Swiderski ◽  
Andy D. Perkins ◽  
Bindu Nanduri ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Respiratory Disease ◽  
Type I Interferon ◽  
Bovine Respiratory Disease ◽  
Transcriptomic Analysis ◽  
Type I ◽  
Antiviral Defense ◽  
High Quality Research ◽  
Immunological Mechanisms ◽  
Unmapped Reads

Abstract BackgroundDespite decades of extensive research, bovine respiratory disease (BRD) remains the most devastating disease in beef cattle production. Clinical diagnosis relies upon non-specific signs, which lack sensitivity. Thus, post-weaned beef cattle are often metaphylactically administered antimicrobials at facility arrival, which poses concerns regarding antimicrobial stewardship and resistance. Additionally, there is a lack of high-quality research that addresses the gene-by-environment interactions that underlie why some cattle that develop BRD die while others survive. Therefore, it is necessary to decipher the underlying host genomic factors associated with BRD mortality versus survival to help determine BRD risk and severity. Using transcriptomic analysis of at-arrival whole blood samples from cattle that died of BRD, as compared to those that developed signs of BRD but lived (n = 3 DEAD, n = 3 ALIVE), we identified differentially expressed genes (DEGs) and associated pathways in cattle that died of BRD. Additionally, we evaluated unmapped reads, which are often overlooked within transcriptomic experiments.Results69 DEGs (FDR < 0.10) were identified between ALIVE and DEAD cohorts. Several DEGs possess immunological and proinflammatory function and associations with TLR4 and IL6. Biological processes, pathways, and disease phenotype associations related to type-I interferon production and antiviral defense were enriched in DEAD cattle at arrival. Unmapped reads aligned primarily to various ungulate assemblies, but failed to align to viral assemblies.ConclusionThis study further revealed increased proinflammatory immunological mechanisms in cattle that develop BRD. DEGs upregulated in DEAD cattle were predominantly involved in innate immune pathways typically associated with antiviral defense, although no viral genes were identified within unmapped reads. Our findings provide genomic targets for further analysis in cattle at highest risk of BRD, suggesting that mechanisms related to type I interferons and antiviral defense may be indicative of viral respiratory disease at arrival and contribute to eventual BRD mortality.

scholarly journals Respiratory viruses identified in western Canadian beef cattle by metagenomic sequencing and their association with bovine respiratory disease

2019 ◽  
Vol 66 (3) ◽  
pp. 1379-1386 ◽  
Author(s):  
Maodong Zhang ◽  
Janet E. Hill ◽  
Champika Fernando ◽  
Trevor W. Alexander ◽  
Edouard Timsit ◽  
...  
Keyword(s):  
Beef Cattle ◽  
Respiratory Disease ◽  
Bovine Respiratory Disease ◽  
Respiratory Viruses ◽  
Metagenomic Sequencing

scholarly journals Social history and exposure to pathogen signals modulate social status effects on gene regulation in rhesus macaques

2019 ◽  
Vol 117 (38) ◽  
pp. 23317-23322 ◽  
Author(s):  
Joaquín Sanz ◽  
Paul L. Maurizio ◽  
Noah Snyder-Mackler ◽  
Noah D. Simons ◽  
Tawni Voyles ◽  
...  
Keyword(s):  
Gene Expression ◽  
Social Status ◽  
Social History ◽  
Immune Cell ◽  
Rhesus Macaques ◽  
Expression Patterns ◽  
Social Experience ◽  
Type I ◽  
Gene Expression Response ◽  
Expression Of Genes

Social experience is an important predictor of disease susceptibility and survival in humans and other social mammals. Chronic social stress is thought to generate a proinflammatory state characterized by elevated antibacterial defenses and reduced investment in antiviral defense. Here we manipulated long-term social status in female rhesus macaques to show that social subordination alters the gene expression response to ex vivo bacterial and viral challenge. As predicted by current models, bacterial lipopolysaccharide polarizes the immune response such that low status corresponds to higher expression of genes in NF-κB–dependent proinflammatory pathways and lower expression of genes involved in the antiviral response and type I IFN signaling. Counter to predictions, however, low status drives more exaggerated expression of both NF-κB– and IFN-associated genes after cells are exposed to the viral mimic Gardiquimod. Status-driven gene expression patterns are linked not only to social status at the time of sampling, but also to social history (i.e., past social status), especially in unstimulated cells. However, for a subset of genes, we observed interaction effects in which females who fell in rank were more strongly affected by current social status than those who climbed the social hierarchy. Taken together, our results indicate that the effects of social status on immune cell gene expression depend on pathogen exposure, pathogen type, and social history—in support of social experience-mediated biological embedding in adulthood, even in the conventionally memory-less innate immune system.

#24 Catecholamines enhance viral replication by inhibiting Type I interferon gene expression

2005 ◽  
Vol 19 (4) ◽  
pp. e12-e13
Author(s):  
Alicia Collado-Hidalgo ◽  
Caroline Y. Sung ◽  
Steve W. Cole
Keyword(s):  
Gene Expression ◽  
Viral Replication ◽  
Type I Interferon ◽  
Type I ◽  
Interferon Gene

The Relationships Among Spatiotemporal Gene Expression, Histology, and Biomechanics Following Full-Length Injury in the Murine Patellar Tendon

2011 ◽  
Author(s):  
Nathaniel A. Dyment ◽  
Namdar Kazemi ◽  
Lindsey E. Aschbacher-Smith ◽  
Nicolas J. Barthelery ◽  
Keith Kenter ◽  
...  
Keyword(s):  
Gene Expression ◽  
Patellar Tendon ◽  
Expression Patterns ◽  
Tendon Healing ◽  
Full Length ◽  
Treatment Modalities ◽  
Type I ◽  
Biomechanical Assessment ◽  
Tendon Tissue Engineering ◽  
Natural Healing

Tendon and ligament injuries present a considerable socioeconomic impact as close to 50% of the 32 million musculoskeletal injuries in the US per year include these structures [1]. The inadequate healing in these tissues requires novel treatment modalities. Improving tendon tissue engineering dictates that we better understand the process of natural adult tendon healing. Type-I (Col1) and Type-II (Col2) collagens are important structural proteins in tendon as Col1 is the main collagen type found in the tendon midsubstance while Col2 is expressed at the insertion into bone during development, growth, and healing [2–3]. Expression of Col1 and Col2 has typically been analyzed via qPCR, western blotting, and immunohistochemistry (IHC) during healing. However, the temporal expression of these genes is still poorly understood on a cell-by-cell basis. Our lab has previously studied patellar tendon (PT) healing in NZW rabbits [4]. While the NZW rabbit allows for controlled injuries and accurate biomechanical assessment of healing, it lacks the genetic power that is offered in the mouse. Therefore, pOBCo13.6GFPtpz (Col1) and pCol2ECFP (Col2) double transgenic (DT) reporter mice were created to track spatiotemporal gene expression. Thus, the objectives of this study were to monitor changes in: 1) spatiotemporal Col1 and Col2 gene expression patterns, 2) tissue morphology, and 3) healing biomechanics following a full-length, central PT injury in Col1/Col2 DT mice and to compare these natural healing results to contralateral surgical shams and normal PT in age-matched controls.

scholarly journals A systematic review and network meta-analysis of injectable antibiotic options for the control of bovine respiratory disease in the first 45 days post arrival at the feedlot

2019 ◽  
Vol 20 (2) ◽  
pp. 163-181
Author(s):  
A. M. O'Connor ◽  
D. Hu ◽  
S. C. Totton ◽  
N. Scott ◽  
C. B. Winder ◽  
...  
Keyword(s):  
Systematic Review ◽  
Beef Cattle ◽  
Respiratory Disease ◽  
Citation Index ◽  
Meta Analysis ◽  
Bovine Respiratory Disease ◽  
The United States ◽  
Feedlot Cattle ◽  
Freedom Of Information ◽  
Biological Index

AbstractWe conducted a systematic review and network meta-analysis to determine the comparative efficacy of antibiotics used to control bovine respiratory disease (BRD) in beef cattle on feedlots. The information sources for the review were: MEDLINE®, MEDLINE In-Process and MEDLINE® Daily, AGRICOLA, Epub Ahead of Print, Cambridge Agricultural and Biological Index, Science Citation Index, Conference Proceedings Citation Index – Science, the Proceedings of the American Association of Bovine Practitioners, World Buiatrics Conference, and the United States Food and Drug Administration Freedom of Information New Animal Drug Applications summaries. The eligible population was weaned beef cattle raised in intensive systems. The interventions of interest were injectable antibiotics used at the time the cattle arrived at the feedlot. The outcome of interest was the diagnosis of BRD within 45 days of arrival at the feedlot. The network meta-analysis included data from 46 studies and 167 study arms identified in the review. The results suggest that macrolides are the most effective antibiotics for the reduction of BRD incidence. Injectable oxytetracycline effectively controlled BRD compared with no antibiotics; however, it was less effective than macrolide treatment. Because oxytetracycline is already commonly used to prevent, control, and treat BRD in groups of feedlot cattle, the use of injectable oxytetracycline for BRD control might have advantages from an antibiotic stewardship perspective.

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