bluuebunny/crossref_metadata_2025 huggingface dataset:
Characterization of BioID tagging systems in budding yeast and exploring the interactome of the Ccr4-Not complex
Authors: Pfannenstein Jeffrey , Tyryshkin Misha , Gulden Moira E , Doud Emma H , Mosley Amber L , Reese Joseph C
Published: September 2024

The modified Escherichia coli biotin ligase BirA* was the first developed for proximity labeling of proteins (BioID). However, it has low activity at temperatures below 37°C, which reduces its effectiveness in organisms growing at lower temperatures, such as budding yeast. Multiple derivatives of the enzymes have been engineered, but a thorough comparison of these variations of biotin ligases and the development of versatile tools for conducting these experiments in Saccharomyces cerevisiae would benefit the community. Here, we designed a suite of vectors to compare the activities of biotin ligase enzymes in yeast. We found that the newer TurboID versions were the most effective at labeling proteins, but they displayed low constitutive labeling of proteins even in the absence of exogenous biotin, due to biotin contained in the culture medium. We describe a simple strategy to express free BioID enzymes in cells that can be used as an appropriate control in BioID studies to account for the promiscuous labeling of proteins caused by random interactions between bait-BioID enzymes in cells. We also describe chemically induced BioID systems exploiting the rapamycin-stabilized FRB-FKBP interaction. Finally, we used the TurboID version of the enzyme to explore the interactome of different subunits of the Ccr4-Not gene regulatory complex. We find that Ccr4-Not predominantly labeled cytoplasmic mRNA regulators, consistent with its function in mRNA decay and translation quality control in this cell compartment.
Hiatal hernia: risk factors, and clinical and endoscopic aspects in gastroscopy
Authors: Abu-Freha Naim , Guterman Revital , Elhayany Ruhama , Yitzhak Avraham , Hudes Shira Sophie , Fich Alexander
Published: September 2024

Background

Hiatal hernia (HH) is a common finding in gastroscopy. The aim of the present study was to investigate the frequency rate of HH among patients who underwent esophagogastroduodenoscopy (EGD) according to their age, gender, and procedural indication.

Methods

A multicenter, retrospective study including all EGDs was conducted across seven endoscopy departments between 2016 and 2021. Demographic information, procedural indications, and findings from the initial EGD were collected.

Results

Of the 162,608 EGDs examined, 96,369 (59.3%) involved female patients. HH was identified in 39,619 (24.4%) of all EGDs performed, comprising small HH in 31,562 (79.6%) and large HH in 3,547 (9.0%). The frequency of HH was 16.5% in the age group of ≤50 years and 37.3% in those aged ≥81 years. HH was diagnosed in 38.7% (11,370) of patients with heartburn/reflux symptoms, 31.5% of those with dysphagia, 28.5% of those with positive fecal occult blood tests, and 24.3% of those who would undergo bariatric surgery. Age (odds ratio 1.030), female gender (odds ratio 1.309), reflux symptoms (odds ratio 2.314), and dysphagia (odds ratio 1.470) were identified as predictors for HH.

Conclusions

Risk factors for HH diagnosed by EGD in symptomatic patients were shown to be advanced age, female gender, and the presence of heartburn or dysphagia.
New Evidence of Healthier Aging: Positive Cohort Effects on Verbal Fluency
Authors: Massa Fernando , Marroig Alejandra , Rodgers Joe , Hoffer Scott M , Muniz-Terrera Graciela
Published: September 2024

Background and Objectives

Cross-sectional studies have shown improvements in cognition in later-born cohorts. However, it remains unclear whether these cohort effects extend beyond cognitive levels and are also detectable in the rate of age-related cognitive decline. Additionally, evidence is scarce on the presence and consistency of cohort effects throughout different segments of the distribution of cognitive trajectories.

Research Design and Methods

This study evaluates the existence and variability of cohort effects across the entire distribution of aging-related trajectories of verbal fluency. With this purpose, we develop sex and education-adjusted longitudinal norms of verbal fluency using data from 9 waves of the English Longitudinal Study of Aging (ELSA) by fitting quantile mixed models. The effect of age was modeled using splines to assess birth cohort effects, after grouping individuals in 5-year groups from 1920 to 1950 according to their age at study entry. To test for possible cohort effects across the 10th, 50th, and 90th quantiles, the coefficients associated with the splines were allowed to vary among cohorts.

Results

Our results suggest that, consistently across longitudinal quantiles, decline in verbal fluency across age is less pronounced for later-born individuals (p < .001), supporting the hypothesis of cohort effects. Additionally, we also found that quantiles of verbal fluency at any age are shifted upwards in later-born cohorts compared to those in earlier-born cohorts.

Discussion and Implications

These results enhance our understanding of cognitive decline in older adults by demonstrating that cohort effects on cognition are observable both cross-sectionally and longitudinally, affecting the entire range of verbal fluency trajectories.
Early-Life Diet Diversity and the Subsequent Risk of Inflammatory Bowel Disease: Findings From Two Scandinavian Birth Cohorts
Authors: Guo Annie , Ludvigsson Johnny , Hård af Segerstad Elin M , Brantsæter Anne Lise , Andersson Björn , Størdal Ketil , Mårild Karl
Published: September 2024

Background

Diet diversity in early childhood promotes microbial diversity, influences the developing immune system, and has been linked to a reduced risk of immune-mediated diseases. This study aimed to determine the association between childhood diet diversity and later inflammatory bowel disease (IBD), for which data are limited.

Methods

Questionnaire data from the population-based birth cohorts All Babies in Southeast Sweden (ABIS) and the Norwegian Mother, Father, and Child Cohort (MoBa), including participants from Southeast Sweden and Norway, were used to estimate a diet diversity score at ages 1 and 3 years. This score represents the diversity of intakes across 5 food groups comprising 11 subgroups. A higher score signifies higher diet diversity. We used linked health registry data to identify IBD diagnoses up to the year 2021. Cox regression and random-effect models were used to estimate pooled hazard ratios (aHRs) adjusted for sociodemographics, breastfeeding, and early-life antibiotic use.

Results

Among 81 272 children with 1 304 325 person-years of follow-up, 307 developed IBD. Diet diversity at ages 1 and 3 years was in pooled analyses not associated with later IBD (per one-unit increase, aHR = 0.96 [95% CI = 0.81-1.14] and aHR = 0.96 [95% CI = 0.83-1.11]). In MoBa, but not ABIS, a higher diet diversity at 1 and 3 years of age was inversely associated with ulcerative colitis (UC) (per one-unit increase, aHR = 0.78 [95% CI = 0.66-0.94] and aHR = 0.78 [95% CI = 0.65-0.95]). Still, pooled aHRs for UC as well as Crohn’s disease approximated one.

Conclusions

In this prospective study of 2 Scandinavian birth cohorts, no association was observed between early-life diet diversity and the subsequent risk of IBD.
Convergence of gut phage communities but not bacterial communities following wild mouse bacteriophage transplantation into captive house mice
Authors: Čížková Dagmar , Payne Pavel , Bryjová Anna , Ďureje Ľudovít , Piálek Jaroslav , Kreisinger Jakub
Published: September 2024

Bacteriophages are abundant components of vertebrate gut microbial communities, impacting bacteriome dynamics, evolution, and directly interacting with the superhost. However, knowledge about gut phageomes and their interaction with bacteriomes in vertebrates under natural conditions is limited to humans and non-human primates. Widely used specific-pathogen-free (SPF) mouse models of host-microbiota interactions have altered gut bacteriomes compared to wild mice, and data on phageomes from wild or other non-SPF mice are lacking. We demonstrate divergent gut phageomes and bacteriomes in wild and captive non-SPF mice, with wild mice phageomes exhibiting higher alpha-diversity and interindividual variability. In both groups, phageome and bacteriome structuring mirrored each other, correlating at the individual level. Re-analysis of previous data from phageomes of SPF mice revealed their enrichment in Suoliviridae crAss-like phages compared to our non-SPF mice. Disrupted bacteriomes in mouse models can be treated by transplanting healthy phageomes, but the effects of phageome transplants on healthy adult gut microbiota are still unknown. We show that experimental transplantation of phageomes from wild to captive mice did not cause major shifts in recipient phageomes. However, the convergence of recipient-to-donor phageomes confirmed that wild phages can integrate into recipient communities. The differences in the subset of integrated phages between the two recipient mouse strains illustrate the context-dependent effects of phage transplantation. The transplantation did not impact recipient gut bacteriomes. This resilience of healthy adult gut microbiomes to the intervention has implications for phage allotransplantation safety.
The use of dual β-lactams to restore susceptibility of Mycobacterium avium complex
Authors: Al-Jabri Maha Y , Dousa Khalid M , Wilson Brigid M , Bonomo Robert A
Published: September 2024

Background

The Mycobacterium avium complex (MAC) are non-tuberculous mycobacteria responsible for chronic and debilitating conditions. Guideline-recommended therapy for MAC is a combination of clarithromycin/azithromycin, ethambutol and a rifamycin. However, culture conversion rates with this regimen are 67%. Alternative treatment options are needed. Recent findings of β-lactam combinations in the treatment of other mycobacterial diseases have been promising. The proposed mechanism is an additive inhibition of multiple enzymes in the peptidoglycan synthesis pathway by the β-lactam combinations. Given the similarity in cell wall structures of MAC and M. abscessus, we hypothesize that using dual β-lactams will result in interruption of peptidoglycan synthesis in MAC and reduction of MIC. In this study, we sought to determine the MIC of meropenem in combination with ceftaroline, cefdinir and cefuroxime in MAC.

Methods

A total of 31 clinical MAC isolates were used for susceptibility testing using broth microdilution method. MICs were tested for meropenem, ceftaroline, cefdinir and cefuroxime, alone, as well as combinations of meropenem plus ceftaroline, cefdinir, or cefuroxime.

Results

In vitro MAC susceptibility to meropenem was significantly enhanced with the addition of ceftaroline, cefdinir, and cefuroxime. This effect was most significant with addition of ceftaroline and cefdinir, with a change of meropenem MIC50/MIC90 from 16/32 to 0.125/0.5 and 0.125/4 mg/L, respectively (P value ≤0.0001, Wilcoxon signed-rank test).

Conclusions

This study demonstrates that the susceptibility of MAC to meropenem is restored with the addition of ceftaroline and cefdinir. These findings underscore the potential effectiveness of combining β-lactams as an alternative therapeutic strategy for MAC infections.
New commercial wipes inhibit the dispersion and adhesion of Staphylococcus aureus and Pseudomonas aeruginosa biofilms
Authors: Di Fermo Paola , Diban Firas , Ancarani Elisabetta , Yu Kelvin , D'Arcangelo Sara , D'Ercole Simonetta , Di Lodovico Silvia , Di Giulio Mara , Cellini Luigina
Published: September 2024

Aim

Bacterial biofilms can form on surfaces in hospitals, clinics, farms, and food processing plants, representing a possible source of infections and cross-contamination. This study investigates the effectiveness of new commercial wipes against Staphylococcus aureus and Pseudomonas aeruginosa biofilms (early attachment and formed biofilms), assessing LH SALVIETTE wipes (Lombarda H S.r.l.) potential for controlling biofilm formation.

Methods and results

The wipes efficacy was studied against the early attachment phase and formed biofilm of S. aureus ATCC 6538 and P. aeruginosa ATCC 15442 on a polyvinyl chloride (PVC) surface, following a modified standard test EN 16615:2015, measuring Log10 reduction and cell viability using live/dead staining. It was also evaluated the wipes anti-adhesive activity over time (3 h, 2 4h), calculating CFU.mL−1 reduction. Data were analyzed using t-student test. The wipes significantly reduced both early phase and formed S. aureus biofilm, preventing dispersion on PVC surfaces. Live/dead imaging showed bacterial cluster disaggregation and killing action. The bacterial adhesive capability decreased after short-time treatment (3 h) with the wipes compared to 24 h.

Conclusions

Results demonstrated decreased bacterial count on PVC surface both for early attachment phase and formed biofilms, also preventing the bacterial biofilm dispersion.
Can GPT-3.5 generate and code discharge summaries?
Authors: Falis Matúš , Gema Aryo Pradipta , Dong Hang , Daines Luke , Basetti Siddharth , Holder Michael , Penfold Rose S , Birch Alexandra , Alex Beatrice
Published: September 2024

Objectives

The aim of this study was to investigate GPT-3.5 in generating and coding medical documents with International Classification of Diseases (ICD)-10 codes for data augmentation on low-resource labels.

Materials and Methods

Employing GPT-3.5 we generated and coded 9606 discharge summaries based on lists of ICD-10 code descriptions of patients with infrequent (or generation) codes within the MIMIC-IV dataset. Combined with the baseline training set, this formed an augmented training set. Neural coding models were trained on baseline and augmented data and evaluated on an MIMIC-IV test set. We report micro- and macro-F1 scores on the full codeset, generation codes, and their families. Weak Hierarchical Confusion Matrices determined within-family and outside-of-family coding errors in the latter codesets. The coding performance of GPT-3.5 was evaluated on prompt-guided self-generated data and real MIMIC-IV data. Clinicians evaluated the clinical acceptability of the generated documents.

Results

Data augmentation results in slightly lower overall model performance but improves performance for the generation candidate codes and their families, including 1 absent from the baseline training data. Augmented models display lower out-of-family error rates. GPT-3.5 identifies ICD-10 codes by their prompted descriptions but underperforms on real data. Evaluators highlight the correctness of generated concepts while suffering in variety, supporting information, and narrative.

Discussion and Conclusion

While GPT-3.5 alone given our prompt setting is unsuitable for ICD-10 coding, it supports data augmentation for training neural models. Augmentation positively affects generation code families but mainly benefits codes with existing examples. Augmentation reduces out-of-family errors. Documents generated by GPT-3.5 state prompted concepts correctly but lack variety, and authenticity in narratives.
PheW2P2V: a phenome-wide prediction framework with weighted patient representations using electronic health records
Authors: Guo Jia , Kiryluk Krzysztof , Wang Shuang
Published: September 2024

Objective

Electronic health records (EHRs) provide opportunities for the development of computable predictive tools. Conventional machine learning methods and deep learning methods have been widely used for this task, with the approach of usually designing one tool for one clinical outcome. Here we developed PheW2P2V, a Phenome-Wide prediction framework using Weighted Patient Vectors. PheW2P2V conducts tailored predictions for phenome-wide phenotypes using numeric representations of patients’ past medical records weighted based on their similarities with individual phenotypes.

Materials and Methods

PheW2P2V defines clinical disease phenotypes using Phecode mapping based on International Classification of Disease codes, which reduces redundancy and case-control misclassification in real-life EHR datasets. Through upweighting medical records of patients that are more relevant to a phenotype of interest in calculating patient vectors, PheW2P2V achieves tailored incidence risk prediction of a phenotype. The calculation of weighted patient vectors is computationally efficient, and the weighting mechanism ensures tailored predictions across the phenome. We evaluated prediction performance of PheW2P2V and baseline methods with simulation studies and clinical applications using the MIMIC-III database.

Results

Across 942 phenome-wide predictions using the MIMIC-III database, PheW2P2V has median area under the receiver operating characteristic curve (AUC-ROC) 0.74 (baseline methods have values ≤0.72), median max F1-score 0.20 (baseline methods have values ≤0.19), and median area under the precision-recall curve (AUC-PR) 0.10 (baseline methods have values ≤0.10).

Discussion

PheW2P2V can predict phenotypes efficiently by using medical concept embeddings and upweighting relevant past medical histories. By leveraging both labeled and unlabeled data, PheW2P2V reduces overfitting and improves predictions for rare phenotypes, making it a useful screening tool for early diagnosis of high-risk conditions, though further research is needed to assess the transferability of embeddings across different databases.

Conclusions

PheW2P2V is fast, flexible, and has superior prediction performance for many clinical disease phenotypes across the phenome of the MIMIC-III database compared to that of several popular baseline methods.
269 Evaluation of changes in the activity of group-housed nursery pigs exposed to an endotoxin challenge using the NUtrack Livestock Monitoring System
Authors: Parrish Brooke L , Holliday Aaron J , Hulbert Lindsey E , Goering Mikayla J , Forster Storey L , Vieregger Avery E , Jaberi-Douraki Majid , Mote Benny E , Schmidt Ty B
Published: September 2024

The objective of this study was to evaluate the changes in activity of group-housed, newly weaned, Duroc-sired crossbred commercial pigs exposed to a lipopolysaccharide (LPS) challenge. At weaning, pigs [n = 192, body weight (BW) = 5.73 ± 1.8 kg] were stratified by sex, litter, and weaning weight and randomly assigned to one of three treatment groups (16 pigs/pen, 4 pens/treatment). Treatments were: 1) control – saline-injected (SAL), 2) 50% challenged (LPS50) – one-half of the pigs in a pen (n = 8) were challenged with LPS, the remaining 8 pigs received saline, and 3) 100% LPS challenged (LPS100) – all pigs in a pen were challenged with LPS. Pigs in the SAL group and 32 in the LPS50 group received a 3.0 mL subcutaneous saline injection. The remaining pigs in the LPS50 group and all pigs in the LPS100 group received a 3.0 mL subcutaneous LPS (E. coli O111:B4) injection dissolved in sterile saline calculated to challenge each pig with 300 µg/kg of BW. Pigs were continuously monitored (24 h/d) during the 42-d nursery period via the NUtrack Livestock Monitoring System. Activity traits included distance traveled (m/d), time spent at the feeder (% of day), and time spent standing (% of day) and were analyzed using the PROC GLIMMIX procedure of SAS. When main effects or interactions were significant (P ≤ 0.05), specific comparisons were made using the PDIFF option in SAS. Changes in activities were observed (P ≤ 0.03) in both LPS groups for the first 3 to 4 d after the challenge. During this period, pigs in the LPS50 and LPS100 groups walked less (P ≤ 0.001) and spent less (P ≤ 0.002) time standing and less (P ≤ 0.03) time at the feeder when compared with pigs in the SAL group. By d 5, activities were similar (P ≥ 0.07) between the three treatment groups and remained similar (P ≥ 0.38) until 9 d after the LPS challenge. Starting on d 11 and continuing until d 15, there was an increase (P ≤ 0.03) in both meters walked/d and time spent standing for pigs in the LPS100 group compared with the SAL group. Furthermore, on d 10 to 15, pigs in the LPS50 and LPS100 groups spent more (P ≤ 0.05) time at the feeder when compared with the pigs in the SAL group. However, increased time at the feeder from d 9 to 15 for LPS100 did not offset the impact of the LPS challenge on nursery exit weight. At exit (d 42), pigs in the LPS100 group had reduced (P ≤ 0.04) BW and average daily gain, when compared with the pigs in the SAL group. Overall, these results suggest that changes in activities following an LPS challenge are not limited to the days immediately following the challenge. Although an LPS challenge elicits a short-lived (3 - 4 d) immune response, its effects can be long-lasting.
271 Does social buffering amongst familiar weaned beef calves mitigate castration stressors?
Authors: Parsons Rebecca L , Brezina Caleb , Dewell Grant A , Dewell Renee D , Johnson Anna K , Haley Derek B , Millman Suzanne T
Published: September 2024

Co-mingling of beef feeder calves from multiple sources results in biological and behavioral stressors. This study is part of a project exploring social relationships between individual beef cattle and potential benefits of social buffering during stress events. Here, the specific objective was to explore whether feeder calves form preferential relationships which buffer them from surgical castration pain. Within the experiment, two treatment groups were established: Familiar calves were defined as calves who shared a source farm with two other calves in the pen, and Unfamiliar calves were defined as calves who did not share a source with any other pen-mates. It was hypothesized that Familiar calves would exhibit more lying, fewer pain-related behaviors, and fewer agonistic interactions following surgical castration than Unfamiliar pen-mates. Weaned beef bull calves [n = 102, body weight (BW) range ± SD = 112.95 to 370.10 ± 67.8 kg] from 23 source farms were randomly assigned to home pens, each comprised of three Familiar calves and three Unfamiliar calves. Cameras placed above the pens recorded video from which postural (standing and lying), social (agonistic and bunk displacements) and pain-related behaviors (wound checking and hind leg stamping) were quantified. Cattle were handled through a hydraulic squeeze chute once weekly over four consecutive weeks for data collection and standard processing procedures. On d 14 relative to arrival, calves were surgically castrated with multimodal pain mitigation. During all processing events, calves were marked with livestock paint for behavioral observations. Behavior was observed continuously for 15 min at five different time points (0 h, 1 h, 4 h, 24 h, 48 h) relative to when the last calf returned to the home pen after processing, and researchers were blind to treatment allocation. These time periods corresponded to expected periods when pain was absent and present based on duration of local anesthesia and systemic pain relief. Calf was the experimental unit. For the purpose of this abstract, data from the 48 h periods following d 7 and 14 were analyzed using the PROC GLIMMIX procedure of SAS; the model included treatment (Familiar, Unfamiliar) by week interaction. A P-value of ≤ 0.05 was considered significantly different. Regardless of treatment, preliminary analyses identified decreased lying (P < 0.02) and increased wound checking (P < 0.01) 48h following castration (d 14) when compared with the previous week (d 7). There were no observed differences for hindleg stamping (P = 0.2), agonistic behaviors (P > 0.06) or bunk displacement (P = 0.09). Based on preliminary analyses, we did not observe evidence of social buffering effects on castration stress during the immediate post-surgical period.
141 Genomic selection for heat stress resilience in pigs: Advancements, applications, and challenges
Authors: Johnson Jay S , Brito Luiz F
Published: September 2024

Heat stress is a critical challenge to swine productivity and welfare that causes economic losses and endangers food security. As temperatures continue to increase in most pig producing regions, the effects of heat stress on pig production will become more apparent. The detrimental effects of postnatal heat stress on pig performance and welfare are well-defined. Furthermore, data on the effects of in utero heat stress in pigs describes lifelong production and welfare deficits that may be transgenerational. Despite its economic implications and transgenerational effects, heat stress mitigation strategies remain underexplored. Genomic selection offers a promising avenue for addressing swine heat stress, targeting resilient swine phenotypes to minimize adverse outcomes. However, challenges persist in integrating thermotolerance traits with traditional performance metrics, as improved thermotolerance is often unfavorably correlated with production traits. Therefore, effective selection strategies require balancing productive efficiency with climatic resilience and animal welfare breeding goals. As climate change continues to intensify the frequency and severity of heat stress, innovative approaches that prioritize resilience and adaptability are needed to safeguard swine productivity and welfare.
88 The impact of trait measurement error on quantitative genetic analysis
Authors: Bi Ye , Huang Yijian , Morota Gota
Published: September 2024

The accuracy of trait measurements greatly affects the quality of downstream genetic analyses. With the advancement of three-dimensional sensor cameras and computer vision techniques, there is a growing trend to adopt these new tools for on-farm data collection as they can reduce labor and facilitate the collection of large phenotypic data sets across diverse populations. Pig body weight (BW) values estimated 1) manually using a digital scale, and 2) from videos using computer vision can be considered as two different measurements of the same trait because the source of phenotyping error is different. In other words, BW is controlled by the same set of causal loci, but by different phenotyping errors, and thus has different heritabilities. Previous research has shown that trait measurement error, defined as the difference between manually collected phenotypes and image-derived phenotypes, may be influenced, at least in part, by genetic factors. This suggests that trait measurement error is systematic rather than random, and thus, more likely to lead to misleading downstream results when used in quantitative genetic analysis. Therefore, in this study, we investigated the impact of trait measurement error on the genetic analysis of pig BW. Specifically, the objectives of this study were to 1) estimate trait measurement error from manually collected and image-derived pig BW, and 2) estimate genomic heritability for trait measurement error. Ground-truth BW data were collected manually using a digital weighing system for 540 pigs at five different time points over 3 mo. In addition, image-derived BW were estimated by training models on video data captured by a depth camera. A total of four image analysis machine learning and deep learning models were used, including adaptive thresholding segmentation coupled with either ordinary least squares or random forests, and deep regression based on ResNet50 and Xception. Coefficients of determination for image-derived and ground truth BW were at least 0.95 across time points. Genomic heritability estimates for manual and image-derived BW were mostly identical across time points (ranging from 0.23 to 0.54), indicating that manually measured and image-derived phenotypes yield the same genetic results. In addition, genomic heritability estimates for measurement error were consistently negligible, indicating that trait measurement errors in pig BW do not contain systematic errors that could bias downstream genetic analysis.
119 Awardee Talk: Decoding genomic predictions and genome-wide association in large populations
Authors: Lourenco Daniela , Bermann Matias , Cesarani Alberto , Tsuruta Shogo , Misztal Ignacy
Published: September 2024

Data recording is an integral part of breeding programs. Some breed associations and breeding companies keep historical data that may go back to the 1950s. While pruning old data can help decrease computing costs without sacrificing accuracy, this practice is avoided by most livestock industries. Besides phenotypes and pedigree, genomic information has been accumulating very fast, and dealing with that has become the biggest challenge in the genomic selection era. There are currently more than 8.5 million genotyped dairy cattle and 1.5 million Angus cattle in the US. We recently ran genomic evaluations for almost 4 million genotyped animals, 30 million animals in the pedigree, and 45 million phenotypes for five different breeds, and this talk will describe how these large-scale genomic evaluations are possible under single-step GBLUP (ssGBLUP). In ssGBLUP, a genomic relationship matrix (G) is needed, which may take around 116 TB to keep in memory (RAM) for 4 million genotyped animals. Although millions of animals can be genotyped, the dimensionality of the genomic information is limited, meaning there is a limited set of genotyped individuals representing the independent chromosome segments in the population (i.e., the non-redundant information). The dimensionality is around 6 k in pigs and chickens and 15 k in cattle, which are considered the “core” animals. This reduced rank is exploited to reduce computing costs by creating a generalized, sparse inverse of G with an approximately linear cost in computing and storage. In multi-breed evaluations, the dimensionality should be assessed within each breed to maximize the GEBV prediction accuracy. The model-based accuracy of GEBV is also an important piece of information to help selection but cannot be easily obtained in large, genotyped populations. Our recently developed algorithm also considers the dimensionality of genomic information and uses block sparse inversion to approximate prediction error (co)variance (PEC) for genotyped animals. With PEC for core animals, computing PEC for SNP is trivial, and the latter is used to obtain p-values for SNP effects in genome-wide association studies (GWAS). Using large amounts of information in GWAS may improve the resolution and discovery. Exploiting the limited dimensionality of genomic information helped lift computing limitations for ssGBLUP genomic evaluations and GWAS in large, genotyped populations. Because of that, ssGBLUP became a popular method for genomic selection in livestock. Although this method is quite efficient now, the ever-increasing number of genotyped animals will pose future challenges that will be addressed by constantly changing algorithms and evolving computing power.
121 Copy number variation: From mapping to variance components in Holsteins
Authors: Ladeira Giovanni C , Pinedo Pablo J , Santos Jose E P , Thatcher William W , Rezende Fernanda M
Published: September 2024

Copy number variations (CNVs) modify transcription levels mainly through changing genes and regulatory elements dosages. Hence, CNVs can contribute to the additive genetic variance of quantitative traits, which might not be fully captured by SNPs. Here, CNVs were mapped from 3,601 Holsteins and their contribution to complex traits was explored by i) quantitative trait loci (QTL) enrichment analysis, and ii) variance component analysis for metritis (1 = disease, 0 = no disease). The 4,113 CNVs derived from high-density (777k) genotypic information were compiled into 1,184 CNV regions (CNVRs) overlapping 7,832 QTLs reported in dairy cattle and available in the AnimalQTLdb. Fisher’s exact test was applied to perform the QTL enrichment analysis followed by False Discovery Rate (FDR) correction. Then, QTLs overlapping CNVRs were enriched for traits when the corrected P-value (PFDR) was lower than 0.05. For variance components estimation, genomic information from all CNVs loci was used to build the CNV-derived genomic relationship matrix (CNV_GRM). CNV loci showing double deletions, single deletions, and normal state in the population were coded as 0, 1, and 2, respectively, whereas CNV loci presenting normal state, single duplications, and double duplications were coded as 0, 1, and 2, respectively. Given that some CNVs presented both deletions and duplications at the same position in the population, these mixed-CNVs were treated as two distinct CNVs loci, one to represent deletions and the other to represent duplications. The variance components for metritis were estimated by fitting either only a SNP-derived GRM (SNP_GRM) or jointly SNP_GRM and CNV_GRM considering 3,272 cows in models that included the female category and farm-year-season as fixed effects. QTLs overlapped with CNVRs were enriched for milk (e.g., milk fat yield, milk yield, and milk protein percentage), reproduction (e.g., calving ease, non-return rate, and heat intensity), exterior (e.g., teat length, udder depth, and udder height), production (e.g., length of productive life, lifetime profit index, and net merit), and health traits (e.g., immune globulin G level, somatic cell, and bovine respiratory susceptibility). Regarding variance components, copy number variations were able to capture a fraction of the additive genetic variance not captured by SNPs alone, increasing the heritability estimate for metritis. In summary, our findings suggest that CNVs overlap QTLs associated with economically important traits more than only by chance and CNVs can capture additional additive genetic variance not fully captured by SNPs alone.
118 DHGLMF90: A software tool using double hierarchical generalized linear models for estimating the genetic heterogeneity of residual variance
Authors: Munera Alejandra Alvarez , Bermann Matias , Escriche Noelia Ibáñez , Rebollo Cristina Casto , Misztal Ignacy , Lourenco Daniela
Published: September 2024

In animal breeding, there is a growing interest in selecting animals that exhibit uniform responses to environmental conditions, aiming for product consistency as a desirable breeding objective. This could be achieved by modeling heteroskedastic residuals when estimating breeding values through a hierarchical single-trait model that includes a mean and dispersion part. The latter could be influenced by genetic and non-genetic features. Bayesian methods can estimate heteroskedastic residuals using the Metropolis-Hastings algorithm, which is a slow and inefficient approach. Double hierarchical generalized linear models (DHGLM) provide a faster alternative to Bayesian methods. This study aimed to develop software named DHGLMF90 to implement DHGLM using a highly efficient algorithm to accurately estimate heterogeneous residual variances and breeding values, particularly suited for handling large datasets. We improved the reweighted least squares algorithm (IRWLS) to enhance convergence properties compared with prior implementations. IRWLS iteratively computes variance components and leverages them for a bivariate model, covering both the mean and dispersion part of the original model. In DHGLMF90, variance component estimation is performed using REML through BLUPF90+. The software was tested using both simulated and real datasets, the latter from previous studies. Additionally, the simulations were replicated to ensure a comprehensive evaluation of the DHGLMF90 performance. Results indicated that, in most cases, there were no significant differences in estimation compared with results obtained from previous studies. DHGLMF90 converged in order of magnitude faster than Bayesian methods. Future developments will include analyzing datasets with genomic information and multiple-trait models.
202 Longitudinal comparative transcriptomics of dairy cattle at different altitudes reveals unique mechanisms underlying plateau hypoxia adaptation
Authors: Fang Qianhai , Zhang Hailiang , Wang Yachun
Published: September 2024

The adaptation of livestock to high altitude hypoxic environment (plateau hypoxia adaptation) is important as they have a key role in the socio-economic conditions of the local residents. However, the underlying molecular mechanisms of plateau hypoxia adaptation of livestock are poorly understood. This study was objective to 1) construct the longitudinal transcriptional profiles of dairy cattle across five development stages; 2) reveal the transcriptomic changes of peripheral blood under different altitudes environment; and 3) identify key genes involved in plateau hypoxia adaptation in bovine. In this study, 109 peripheral blood samples from 70 Holstein cattle were performed whole transcriptome sequencing, including 56 at high altitude (> 3600 m) at five development stages (1, 2, 6, 12 and 18 mo) from 56 individuals, and 53 at low altitude (~1000 m) at three development stages (1, 2 and 6 mo) from 14 individuals. The peripheral transcriptional profile was obtained for high altitude cattle at five development stages, and for low altitude cattle for three development stages. By the transcriptome profile analysis in plateau cattle across five development stages, it was found that there were significant differences on mRNA transcriptome at different stages, and a noticeable shift occurred between 2 mo and 6 mo. By a comparative analysis of the transcription levels between high and low altitude cattle, 795, 900 and 880 differentially expressed genes (DEGs) were identified at the age of 1, 2 and 6 mo, respectively. The DEGs at three stages were enriched in several cellular communication, hypoxia response, and regulation of blood pressure, and immune-related signaling pathways. Furthermore, there were 64 DEGs shared across three comparative analyses at the three stages. By functional annotation analysis, we observed the shared DEGs of the three stages were enriched in the Notch signaling involved in heart development, regulation of phosphorylation, and positive regulation of MAP kinase activity. In summary, this study revealed the development-related transcriptomic shifts from birth to 18 mo of age in dairy cattle, and preliminarily elucidated the important signaling pathways involved in bovine plateau hypoxia adaptation by comparative analysis between high and low altitude cattle. The results of the current study will drive a better understanding of plateau hypoxia adaptation and can provide molecular targets for future breeding of plateau-adapted dairy cattle.
200 Transcriptomics analyses of mink spleen infected by Aleutian Disease
Authors: Bishop Gregory , Farid Hossain , Do Duy Ngoc , Miar Younes
Published: September 2024

Aleutian disease (AD) is one of the most challenging mink diseases that causes high mortality and affects several economically important traits. Aleutian mink disease virus (AMDV) targets multiple organs and among them, the spleen is one of the major targeted organs. Transcriptomics has been widely used to reveal genes and biological pathways and identify biomarkers for early detection or prevention of diseases. This study aimed to identify genes and pathways related to the host response to AD infection in the spleen via transcriptomic study. Twelve (3 sets of 4 full-sibs) AMDV-free black male mink were housed in the clean section of the animal housing facility at the AD Research Centre (Truro, NS, Canada) between 4 to 7 d before inoculation. Before inoculation, sampling, and euthanasia, animals were anesthetized. The viral inoculum was a 10% (W/V) passage 2 of AMDV prepared from the spleens of mink infected with a local strain and stored at − 80 °C. Animals were intranasally inoculated under sedation with 60 µL of the viral homogenate, corresponding to approximately 300 to 700 ID50. Infected mink were humanely euthanized and the spleen tissues were collected for RNA isolation at 24h (d 1), 48h (d 2), and d 7. Libraries were prepared from total RNA using the Illumina TruSeqTM RNA kit, and were sequenced using the HiScanSQ platform, producing 101 bp reads from each end. The raw RNA-Seq data were cleaned using Cutadapt V1.4.2 and after the cleaning process was completed, 942,803,540 paired-end reads remained to be used in downstream analysis. Differential gene expression analyses revealed most (168) significant differentially expressed (DE) genes between d 1 and d 0 (Control or ADMV-free mink) while fewer DE genes (23) were between d 7 and d 0 (Table 1; Figure 1). A total of 19 DE genes are identified between three pair comparisons and seven of them are directly involved in immune response (FGL2, TLF8, LRP1, SERPINB9, MSR1, C3, PLA2R1, and XCR1). Gene enrichment analyses revealed pathways related to innate immune and fat metabolism which are important for the host mechanism to fight against infections. One of the important pathways is neutrophil degranulation which functions as aiding in the elimination of pathogens and the initiation of the inflammatory process. In conclusion, the current study provides insight into the transcriptomic profiles of the spleen in mink infected with AD. Identified candidate genes might be used for functional studies or as prior information for markers or genomic selection against AD in mink. Further studies in other tissues or single-cell RNA sequencing might deliver more comprehensive pictures of host responses to AD infections.
203 Genome Wide Association Study for reduced dry period in dairy goats
Authors: Galindo Bruno A , Massender Erin , Hermisdorff Isis C , Schenkel Flávio S
Published: September 2024

Canada’s goat herd is about 243,000 animals, with national yearly milk production of approximately 62.6 million L. However, the ongoing import of 182,000 kg of goat cheese highlights the potential for further expansion in milk production within the country. The period between two lactations when females are not producing milk is called the “dry period”, which ranges between 50 to 60 d in Ontario goats. Shortening the dry period without compromising animal health or production would be advantageous for producers. In Ontario, records have revealed a herd where a substantial percentage of animals experience a dry period between lactations as short as one day. A genomic study of this herd could provide an understanding regarding the genetic background of these short dry periods (= 1 d). The goal of this research was to perform a Genome Wide Association Study (GWAS) aiming to identify genes associated with dry period length. A total of 209 Saanen dairy goats with usual dry periods (coded as 0) and 54 with short dry periods (coded as 1) were analyzed. All animals were genotyped using GoatSNP50 Bead Chip from Illumina Inc. and, following genotyping quality control, 44,692 variants were retained for analysis. A GWAS using a mixed linear model implemented in GCTA software version v1.94.1 was performed, employing the “leave-one-chromosome-out” approach, excluding the chromosome containing the candidate SNP from the genetic relationship matrix (GRM) calculation. P-values were adjusted for multiple comparisons using the Benjamini & Hochberg method. Additionally, a qq-plot was used to assess possible inflation of the test statistic, but no inflation (λ=1.03) was observed. Four significant SNPs (FDR < 0.05) associated with short dry periods were identified, all located on chromosome 20. Subsequently, within a 60 k base pair range upstream and downstream of these markers, two candidate genes (OSMR and GHR) and one QTL associated with cannon bone circumference were identified. Of particular interest is the OSMR gene, previously linked to apoptosis in goat mammary gland mRNA profiles and showing increased mRNA and protein levels post-weaning in mice. Additionally, GHR gene has been associated with lactation persistency and various milk production traits in cows. The gene network analysis also revealed interactions between OSMR and GHR. This region on chromosome 20 seems to harbor genes influencing the dry period in dairy goats as well as the milk production traits. Further investigation of this genetic region could help increase the knowledge about the genetic background of the observed short dry periods.
349 The relationship of heart score with hot carcass weight and fat depth in Angus cattle
Authors: Torres-Quijada Isaac F , Speidel Scott E , Bryant Tony C , Retallick-Riley Kelli J , Szasz Josh I , Enns R Mark
Published: September 2024

Congestive Heart Failure (CHF) is a cardiopulmonary condition observed in cattle raised in feedlots situated at elevations above 800 m. This condition leads to right-sided heart failure caused by increased pulmonary vessel pressures and cardiopulmonary remodeling, known as pulmonary hypertension (PH). In cattle experiencing PH, pulmonary arterial pressure (PAP) becomes abnormally high, increasing heart muscle load. This load stretches muscle fibers and enlarges the right side of the heart which can lead to heart failure and death. To assess the severity of PH, animals are assigned a heart score (HS) on a scale ranging from 1 to 5 at harvest. A score of 1 represents a normal heart, while a score of 5 indicates extreme heart remodeling. Understanding the relationship between hot carcass weight (HCW), fat depth (FD), and HS in Angus cattle will provide useful information on the impacts of this condition on feedlot performance and profitability. The objective of this study was to determine if a phenotypic relationship between HCW and FD with HS in Angus-influenced cattle. For this experiment, a total of 798 black, Angus-influenced cattle were used (245 steers, 553 heifers) that were fed near Greeley, CO. The HCW, FD, and HS data from each animal were recorded at harvest. Three general linear models were used to estimate the effects of HS on HCW and FD. Mean HCW and FD were 393.1 kg, (SD = 90.9) and 0.66 mm, (SD = 0.18), respectively, with an average HS of 2.08 (SD = 0.77). For all models, HCW and FD were fit as dependent variables, while lot and HS were included as fixed effects. Model 1 included all HS categories independently. Model 2 divided HS into 2 groups of normal (HS = 1 or 2) or remodeled (HS = 3+). For model 3 HS 3 was removed leaving only HS of 4 or 5 in the remodeled group. For both HCW and FD in Model 1, the overall effect of HS was not significant (P = 0.82 and P = 0.40, respectively). However, when comparing individual scores, animals with a HS = 4 were 15.0 kg lighter for HCW than individuals with a HS = 1 (P < 0.05). Conversely for FD, a non-significant difference (P = 0.74) of -0.33 mm was observed between animals with a HS = 4 versus a HS = 1. Grouping HS into 2 categories in Model 2 did change the outcome, yielding non-significant HCW and FD differences. However, when eliminating the HS = 3 data, a significant reduction in HCW of 16.9 kg (P = 0.05) was observed between the 2 HS groups, whereas non-significant effects on FD remained. These data suggest that at extreme levels of heart remodeling HCW may be extremely impacted negatively.