Identification of candidate genes and enriched biological functions for feed efficiency traits by integrating plasma metabolites and imputed whole genome sequence variants in beef cattle

Abstract Background Feed efficiency is one of the key determinants of beef industry profitability and sustainability. However, the cellular and molecular background behind feed efficiency is largely unknown. This study combines imputed whole genome DNA variants and 31 plasma metabolites to dissect genes and biological functions/processes that are associated with residual feed intake (RFI) and its component traits including daily dry matter intake (DMI), average daily gain (ADG), and metabolic body weight (MWT) in beef cattle. Results Regression analyses between feed efficiency traits and plasma metabolites in a population of 493 crossbred beef cattle identified 5 (L-valine, lysine, L-tyrosine, L-isoleucine, and L-leucine), 4 (lysine, L-lactic acid, L-tyrosine, and choline), 1 (citric acid), and 4 (L-glutamine, glycine, citric acid, and dimethyl sulfone) plasma metabolites associated with RFI, DMI, ADG, and MWT (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using 10,488,742 imputed SNPs, 40, 66, 15, and 40 unique candidate genes were identified as associated with RFI, DMI, ADG, and MWT (P-value < 1 × 10−5), respectively. These candidate genes were found to be involved in some key metabolic processes including metabolism of lipids, molecular transportation, cellular function and maintenance, cell morphology and biochemistry of small molecules. Conclusions This study identified metabolites, candidate genes and enriched biological functions/processes associated with RFI and its component traits through the integrative analyses of metabolites with phenotypic traits and DNA variants. Our findings could enhance the understanding of biochemical mechanisms of feed efficiency traits and could lead to improvement of genomic prediction accuracy via incorporating metabolite data

Integrative analyses of genomic and metabolomic data reveal genetic mechanisms associated with carcass merit traits in beef cattle

Improvement of carcass merit traits is a priority for the beef industry. Discovering DNA variants and genes associated with variation in these traits and understanding biological functions/processes underlying their associations are of paramount importance for more effective genetic improvement of carcass merit traits in beef cattle. This study integrates 10,488,742 imputed whole genome DNA variants, 31 plasma metabolites, and animal phenotypes to identify genes and biological functions/processes that are associated with carcass merit traits including hot carcass weight (HCW), rib eye area (REA), average backfat thickness (AFAT), lean meat yield (LMY), and carcass marbling score (CMAR) in a population of 493 crossbred beef cattle. Regression analyses were performed to identify plasma metabolites associated with the carcass merit traits, and the results showed that 4 (3-hydroxybutyric acid, acetic acid, citric acid, and choline), 6 (creatinine, l-glutamine, succinic acid, pyruvic acid, l-lactic acid, and 3-hydroxybutyric acid), 4 (fumaric acid, methanol, d-glucose, and glycerol), 2 (l-lactic acid and creatinine), and 5 (succinic acid, fumaric acid, lysine, glycine, and choline) plasma metabolites were significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 0.1), respectively. Combining the results of metabolome-genome wide association studies using the 10,488,742 imputed SNPs, 103, 160, 83, 43, and 109 candidate genes were identified as significantly associated with HCW, REA, AFAT, LMY, and CMAR (P-value < 1 × 10(–5)), respectively. By applying functional enrichment analyses for candidate genes of each trait, 26, 24, 26, 24, and 28 significant cellular and molecular functions were predicted for HCW, REA, AFAT, LMY, and CMAR, respectively. Among the five topmost significantly enriched biological functions for carcass merit traits, molecular transport and small molecule biochemistry were two top biological functions associated with all carcass merit traits. Lipid metabolism was the most significant biological function for LMY and CMAR and it was also the second and fourth highest biological function for REA and HCW, respectively. Candidate genes and enriched biological functions identified by the integrative analyses of metabolites with phenotypic traits and DNA variants could help interpret the results of previous genome-wide association studies for carcass merit traits. Our integrative study also revealed additional potential novel genes associated with these economically important traits. Therefore, our study improves understanding of the molecular and biological functions/processes that influence carcass merit traits, which could help develop strategies to enhance genomic prediction of carcass merit traits with incorporation of metabolomic data. Similarly, this information could guide management practices, such as nutritional interventions, with the purpose of boosting specific carcass merit traits

Applying multi-omics data to study the genetic background of bovine respiratory disease infection in feedlot crossbred cattle

Bovine respiratory disease (BRD) is the most common and costly infectious disease affecting the wellbeing and productivity of beef cattle in North America. BRD is a complex disease whose development is dependent on environmental factors and host genetics. Due to the polymicrobial nature of BRD, our understanding of the genetic and molecular mechanisms underlying the disease is still limited. This knowledge would augment the development of better genetic/genomic selection strategies and more accurate diagnostic tools to reduce BRD prevalence. Therefore, this study aimed to utilize multi-omics data (genomics, transcriptomics, and metabolomics) analyses to study the genetic and molecular mechanisms of BRD infection. Blood samples of 143 cattle (80 BRD; 63 non-BRD animals) were collected for genotyping, RNA sequencing, and metabolite profiling. Firstly, a genome-wide association study (GWAS) was performed for BRD susceptibility using 207,038 SNPs. Two SNPs (Chr5:25858264 and BovineHD1800016801) were identified as associated (p-value 2, logCPM>2, and FDR<0.01), 101 differentially expressed (DE) genes were identified. These DE genes significantly (p-value <0.05) enriched several immune responses related functions such as inflammatory response. Additionally, we performed expression quantitative trait loci (eQTL) analysis and identified 420 cis-eQTLs and 144 trans-eQTLs significantly (FDR <0.05) associated with the expression of DE genes. Interestingly, eQTL results indicated the most significant SNP (Chr5:25858264) identified via GWAS was a cis-eQTL for DE gene GPR84. This analysis also demonstrated that an important SNP (rs209419196) located in the promoter region of the DE gene BPI significantly influenced the expression of this gene. Finally, the abundance of 31 metabolites was significantly (FDR <0.05) different between BRD and non-BRD animals, and 17 of them showed correlations with multiple DE genes, which shed light on the interactions between immune response and metabolism. This study identified associations between genome, transcriptome, metabolome, and BRD phenotype of feedlot crossbred cattle. The findings may be useful for the development of genomic selection strategies for BRD susceptibility, and for the development of new diagnostic and therapeutic tools

Selected hematologic and biochemical measurements in African HIV-infected and uninfected pregnant women and their infants: the HIV Prevention Trials Network 024 protocol

Reference values for hematological and biochemical assays in pregnant women and in newborn infants are based primarily on Caucasian populations. Normative data are limited for populations in sub-Saharan Africa, especially comparing women with and without HIV infection, and comparing infants with and without HIV infection or HIV exposure. We determined HIV status and selected hematological and biochemical measurements in women at 20-24 weeks and at 36 weeks gestation, and in infants at birth and 4-6 weeks of age. All were recruited within a randomized clinical trial of antibiotics to prevent chorioamnionitis-associated mother-to-child transmission of HIV (HPTN024). We report nearly complete laboratory data on 2,292 HIV-infected and 367 HIV-uninfected pregnant African women who were representative of the public clinics from which the women were recruited. Nearly all the HIV-infected mothers received nevirapine prophylaxis at the time of labor, as did their infants after birth (always within 72 hours of birth, but typically within just a few hours at the four study sites in Malawi (2 sites), Tanzania, and Zambia. HIV-infected pregnant women had lower red blood cell counts, hemoglobin, hematocrit, and white blood cell counts than HIV-uninfected women. Platelet and monocyte counts were higher among HIV-infected women at both time points. At the 4-6-week visit, HIV-infected infants had lower hemoglobin, hematocrit and white blood cell counts than uninfected infants. Platelet counts were lower in HIV-infected infants than HIV-uninfected infants, both at birth and at 4-6 weeks of age. At 4-6 weeks, HIV-infected infants had higher alanine aminotransferase measures than uninfected infants. Normative data in pregnant African women and their newborn infants are needed to guide the large-scale HIV care and treatment programs being scaled up throughout the continent. These laboratory measures will help interpret clinical data and assist in patient monitoring in a sub-Saharan Africa context

The impact of low erythrocyte density in human blood on the fitness and energetic reserves of the African malaria vector Anopheles gambiae

Background Anaemia is a common health problem in the developing world. This condition is characterized by a reduction in erythrocyte density, primarily from malnutrition and/or infectious diseases such as malaria. As red blood cells are the primary source of protein for haematophagous mosquitoes, any reduction could impede the ability of mosquito vectors to transmit malaria by influencing their fitness or that of the parasites they transmit. The aim of this study was to determine the impact of differences in the density of red blood cells in human blood on malaria vector (Anopheles gambiae sensu stricto) fitness. The hypotheses tested are that mosquito vector energetic reserves and fitness are negatively influenced by reductions in the red cell density of host human blood meals commensurate with those expected from severe anaemia. Methods Mosquitoes (An. gambiae s.s.) were offered blood meals of different packed cell volume(PCV) of human blood consistent with those arising from severe anaemia (15%) and normalPCV (50%). Associations between mosquito energetic reserves (lipid, glucose and glycogen)and fitness measures (reproduction and survival) and blood meal PCV were investigated. Results The amount of protein that malaria vectors acquired from blood feeding (indexed by haematin excretion) was significantly reduced at low blood PCV. However, mosquitoes feeding on blood of low PCV had the same oviposition rates as those feeding on blood of normal PCV, and showed an increase in egg production of around 15%. The long-term survival of An. gambiae s.s was reduced after feeding on low PCV blood, but PCV had no significant impact on the proportion of mosquitoes surviving through the minimal period required to develop and transmit malaria parasites (estimated as 14 days post-blood feeding). The impact of blood PCV on the energetic reserves of mosquitoes was relatively minor. Conclusions These results suggest that feeding on human hosts whose PCV has been depleted due to severe anaemia does not significantly reduce the fitness or transmission potential of malaria vectors, and indicates that mosquitoes may be able exploit resources for reproduction more efficiently from blood of low rather than normal PCV

Extent of compliance with COVID-19 prevention and control guidelines among supermarkets in Kampala Capital City and Mukono Municipality, Uganda

Background Despite the development and enforcement of preventive guidelines by governments, COVID-19 continues to spread across nations, causing unprecedented economic losses and mortality. Public places remain hotspots for COVID-19 transmission due to large numbers of people present; however preventive measures are poorly enforced. Supermarkets are among the high-risk establishments due to the high interactions involved, which makes compliance with the COVID-19 preventive guidelines of paramount importance. However, until now, there has been limited evidence on compliance with the set COVID-19 prevention guidelines. Therefore, this study aimed to measure compliance with the COVID-19 prevention guidelines among supermarkets in Kampala Capital City and Mukono Municipality Uganda. Methods A cross-sectional study was conducted among selected supermarkets in Kampala Capital City and Mukono Municipality in September 2020. A total of 229 supermarkets (195 in Kampala City and 34 in Mukono Municipality) were randomly selected for the study. Data were collected through structured observations on the status of compliance with COVID-19 prevention guidelines, and entered using the KoboCollect software, which was preinstalled on mobile devices (smart phones and tablets). Descriptive statistics were generated to measure compliance to the set COVID-19 Ministry of Health prevention guidelines using Stata 14 software. Results Only 16.6% (38/229) of the supermarkets complied with the COVID-19 prevention and control guidelines. In line with the specific measures, almost all supermarkets 95.2% (218/229) had hand washing facilities placed at strategic points such as the entrance, and 59.8% (137/229) of the supermarkets surveyed regularly disinfected commonly touched surfaces. Only 40.6% and 30.6% of the supermarkets enforced mandatory hand washing and use of face masks respectively for all customers accessing the premises. Slightly more than half, 52.4% (120/229) of the supermarkets had someone or a team in charge of enforcing compliance to COVID-19 measures and more than half, 55.5% (127/229) of the supermarkets had not provided their staff with job-specific training/mentorship on infection prevention and control for COVID-19. Less than a third, 26.2% (60/229) of the supermarkets had an infrared temperature gun for screening every customer, and only 5.7% (13/229) of the supermarkets captured details of clients accessing the supermarket as a measure to ease follow-up. Conclusion This study revealed low compliance with COVID-19 guidelines, which required mandatory preventive measures such as face masking, regular disinfection, social distancing, and hand hygiene. This study suggests the need for health authorities to strengthen enforcement of these guidelines, and to sensitise the supermarket managers on COVID-19 in order to increase the uptake of the different measures

MasakhaNER 2.0: Africa-centric Transfer Learning for Named Entity Recognition

African languages are spoken by over a billion people, but are underrepresented in NLP research and development. The challenges impeding progress include the limited availability of annotated datasets, as well as a lack of understanding of the settings where current methods are effective. In this paper, we make progress towards solutions for these challenges, focusing on the task of named entity recognition (NER). We create the largest human-annotated NER dataset for 20 African languages, and we study the behavior of state-of-the-art cross-lingual transfer methods in an Africa-centric setting, demonstrating that the choice of source language significantly affects performance. We show that choosing the best transfer language improves zero-shot F1 scores by an average of 14 points across 20 languages compared to using English. Our results highlight the need for benchmark datasets and models that cover typologically-diverse African languages

MasakhaPOS: Part-of-Speech Tagging for Typologically Diverse African languages

In this paper, we present AfricaPOS, the largest part-of-speech (POS) dataset for 20 typologically diverse African languages. We discuss the challenges in annotating POS for these languages using the universal dependencies (UD) guidelines. We conducted extensive POS baseline experiments using both conditional random field and several multilingual pre-trained language models. We applied various cross-lingual transfer models trained with data available in the UD. Evaluating on the AfricaPOS dataset, we show that choosing the best transfer language(s) in both single-source and multi-source setups greatly improves the POS tagging performance of the target languages, in particular when combined with parameter-fine-tuning methods. Crucially, transferring knowledge from a language that matches the language family and morphosyntactic properties seems to be more effective for POS tagging in unseen languages

Impact of infection with human immunodeficiency virus-1 (HIV) on the risk of cancer among children in Malawi - preliminary findings

<p>Abstract</p> <p>Background</p> <p>The impact of infection with HIV on the risk of cancer in children is uncertain, particularly for those living in sub-Saharan Africa. In an ongoing study in a paediatric oncology centre in Malawi, children (aged ≤ 15 years) with known or suspected cancers are being recruited and tested for HIV and their mothers or carers interviewed. This study reports findings for children recruited between 2005 and 2008.</p> <p>Methods</p> <p>Only children with a cancer diagnosis were included. Odds ratios (OR) for being HIV positive were estimated for each cancer type (with adjustment for age (<5 years, ≥ 5 years) and sex) using children with other cancers and non-malignant conditions as a comparison group (excluding the known HIV-associated cancers, Kaposi sarcoma and lymphomas, as well as children with other haematological malignancies or with confirmed non-cancer diagnoses).</p> <p>Results</p> <p>Of the 586 children recruited, 541 (92%) met the inclusion criteria and 525 (97%) were tested for HIV. Overall HIV seroprevalence was 10%. Infection with HIV was associated with Kaposi sarcoma (29 cases; OR = 93.5, 95% CI 26.9 to 324.4) and with non-Burkitt, non-Hodgkin lymphoma (33 cases; OR = 4.4, 95% CI 1.1 to 17.9) but not with Burkitt lymphoma (269 cases; OR = 2.2, 95% CI 0.8 to 6.4).</p> <p>Conclusions</p> <p>In this study, only Kaposi sarcoma and non-Burkitt, non-Hodgkin lymphoma were associated with HIV infection. The endemic form of Burkitt lymphoma, which is relatively frequent in Malawi, was not significantly associated with HIV. While the relatively small numbers of children with other cancers, together with possible limitations of diagnostic testing may limit our conclusions, the findings may suggest differences in the pathogenesis of HIV-related malignancies in different parts of the world.</p