Systems biology in animal sciences

Systems biology is a rapidly expanding field of research and is applied in a number of biological disciplines. In animal sciences, omics approaches are increasingly used, yielding vast amounts of data, but systems biology approaches to extract understanding from these data of biological processes and animal traits are not yet frequently used. This paper aims to explain what systems biology is and which areas of animal sciences could benefit from systems biology approaches. Systems biology aims to understand whole biological systems working as a unit, rather than investigating their individual components. Therefore, systems biology can be considered a holistic approach, as opposed to reductionism. The recently developed ‘omics’ technologies enable biological sciences to characterize the molecular components of life with ever increasing speed, yielding vast amounts of data. However, biological functions do not follow from the simple addition of the properties of system components, but rather arise from the dynamic interactions of these components. Systems biology combines statistics, bioinformatics and mathematical modeling to integrate and analyze large amounts of data in order to extract a better understanding of the biology from these huge data sets and to predict the behavior of biological systems. A ‘system’ approach and mathematical modeling in biological sciences are not new in itself, as they were used in biochemistry, physiology and genetics long before the name systems biology was coined. However, the present combination of mass biological data and of computational and modeling tools is unprecedented and truly represents a major paradigm shift in biology. Significant advances have been made using systems biology approaches, especially in the field of bacterial and eukaryotic cells and in human medicine. Similarly, progress is being made with ‘system approaches’ in animal sciences, providing exciting opportunities to predict and modulate animal traits

Gene expression patterns in anterior pituitary associated with quantitative measure of oestrous behaviour in dairy cows

Intensive selection for high milk yield in dairy cows has raised production levels substantially but at the cost of reduced fertility, which manifests in different ways including reduced expression of oestrous behaviour. The genomic regulation of oestrous behaviour in bovines remains largely unknown. Here, we aimed to identify and study those genes that were associated with oestrous behaviour among genes expressed in the bovine anterior pituitary either at the start of oestrous cycle or at the mid-cycle (around day 12 of cycle), or regardless of the phase of cycle. Oestrous behaviour was recorded in each of 28 primiparous cows from 30 days in milk onwards till the day of their sacrifice (between 77 and 139 days in milk) and quantified as heat scores. An average heat score value was calculated for each cow from heat scores observed during consecutive oestrous cycles excluding the cycle on the day of sacrifice. A microarray experiment was designed to measure gene expression in the anterior pituitary of these cows, 14 of which were sacrificed at the start of oestrous cycle (day 0) and 14 around day 12 of cycle (day 12). Gene expression was modelled as a function of the orthogonally transformed average heat score values using a Bayesian hierarchical mixed model on data from day 0 cows alone (analysis 1), day 12 cows alone (analysis 2) and the combined data from day 0 and day 12 cows (analysis 3). Genes whose expression patterns showed significant linear or non-linear relationships with average heat scores were identified in all three analyses (177, 142 and 118 genes, respectively). Gene ontology terms enriched among genes identified in analysis 1 revealed processes associated with expression of oestrous behaviour whereas the terms enriched among genes identified in analysis 2 and 3 were general processes which may facilitate proper expression of oestrous behaviour at the subsequent oestrus. Studying these genes will help to improve our understanding of the genomic regulation of oestrous behaviour, ultimately leading to better management strategies and tools to improve or monitor reproductive performance in bovines

Regional Regulation of Transcription in the Bovine Genome

Eukaryotic genes are distributed along chromosomes as clusters of highly expressed genes termed RIDGEs (Regions of IncreaseD Gene Expression) and lowly expressed genes termed anti-RIDGEs, interspersed among genes expressed at intermediate levels or not expressed. Previous studies based on this observation suggested a dual mechanism of gene regulation, where, in addition to transcription factors, the chromosomal domain influences the expression level of their embedded genes. The objectives here were to provide evidence for the existence of chromosomal regional regulation of transcription in the bovine genome, to analyse the genomic features of genes located within RIDGEs versus anti-RIDGEs and tissue-specific genes versus housekeeping and to examine the genomic distribution of genes subject to positive selection in bovines. Gene expression analysis of four brain tissues and the anterior pituitary of 28 cows identified 70 RIDGEs and 41 anti-RIDGEs (harbouring 3735 and 1793 bovine genes respectively) across the bovine genome which are significantly higher than expected by chance. Housekeeping genes (defined here as genes expressed in all five tissues) were over-represented within RIDGEs but tissue-specific genes (genes expressed in only one of the five tissues) were not. Housekeeping genes and genes within RIDGEs had, in general, higher expression levels and GC content but shorter gene lengths and intron lengths than tissue-specific genes and genes within anti-RIDGES. Our findings suggest the existence of chromosomal regional regulation of transcription in the bovine genome. The genomic features observed for genes within RIDGEs and housekeeping genes in bovines agree with previous studies in several other species further strengthening the hypothesis of selective pressure to keep the highly and widely expressed genes short and compact for transcriptional efficiency. Further, positively selected genes were found non-randomly distributed on the genome with a preference for RIDGEs and regions of intermediate gene expression compared to anti-RIDGEs

Cortical depth dependent population receptive field attraction by spatial attention in human V1

Visual spatial attention concentrates neural resources at the attended location. Recently, we demonstrated that voluntary spatial attention attracts population receptive fields (pRFs) toward its location throughout the visual hierarchy. Theoretically, both a feed forward or feedback mechanism could underlie pRF attraction in a given cortical area. Here, we use sub-millimeter ultra-high field functional MRI to measure pRF attraction across cortical depth and assess the contribution of feed forward and feedback signals to pRF attraction. In line with previous findings, we find consistent attraction of pRFs with voluntary spatial attention in V1. When assessed as a function of cortical depth, we find pRF attraction in every cortical portion (deep, center and superficial), although the attraction is strongest in deep cortical portions (near the gray-white matter boundary). Following the organization of feed forward and feedback processing across V1, we speculate that a mixture of feed forward and feedback processing underlies pRF attraction in V1. Specifically, we propose that feedback processing contributes to the pRF attraction in deep cortical portions

A Pathway Analysis Tool for Analyzing Microarray Data of Species with Low Physiological Information

Pathway information provides insight into the biological processes underlying microarray data. Pathway information is widely available for humans and laboratory animals in databases through the internet, but less for other species, for example, livestock. Many software packages use species-specific gene IDs that cannot handle genomics data from other species. We developed a species-independent method to search pathways databases to analyse microarray data. Three PERL scripts were developed that use the names of the genes on the microarray. (1) Add synonyms of gene names by searching the Gene Ontology (GO) database. (2) Search the Kyoto Encyclopaedia of Genes and Genomes (KEGG) database for pathway information using this GO-enriched gene list. (3) Combine the pathway data with the microarray data and visualize the results using color codes indicating regulation. To demonstrate the power of the method, we used a previously reported chicken microarray experiment investigating line-specific reactions to Salmonella infection as an example

Comparative Analyses by Sequencing of Transcriptomes during Skeletal Muscle Development between Pig Breeds Differing in Muscle Growth Rate and Fatness

Understanding the dynamics of muscle transcriptome during development and between breeds differing in muscle growth is necessary to uncover the complex mechanism underlying muscle development. Herein, we present the first transcriptome-wide longissimus dorsi muscle development research concerning Lantang (LT, obese) and Landrace (LR, lean) pig breeds during 10 time-points from 35 days-post-coitus (dpc) to 180 days-post-natum (dpn) using Solexa/Illumina's Genome Analyzer. The data demonstrated that myogenesis was almost completed before 77 dpc, but the muscle phenotypes were still changed from 77 dpc to 28 dpn. Comparative analysis of the two breeds suggested that myogenesis started earlier but progressed more slowly in LT than in LR, the stages ranging from 49 dpc to 77 dpc are critical for formation of different muscle phenotypes. 595 differentially expressed myogenesis genes were identified, and their roles in myogenesis were discussed. Furthermore, GSK3B, IKBKB, ACVR1, ITGA and STMN1 might contribute to later myogenesis and more muscle fibers in LR than LT. Some myogenesis inhibitors (ID1, ID2, CABIN1, MSTN, SMAD4, CTNNA1, NOTCH2, GPC3 and HMOX1) were higher expressed in LT than in LR, which might contribute to more slow muscle differentiation in LT than in LR. We also identified several genes which might contribute to intramuscular adipose differentiation. Most important, we further proposed a novel model in which MyoD and MEF2A controls the balance between intramuscular adipogenesis and myogenesis by regulating CEBP family; Myf5 and MEF2C are essential during the whole myogenesis process while MEF2D affects muscle growth and maturation. The MRFs and MEF2 families are also critical for the phenotypic differences between the two pig breeds. Overall, this study contributes to elucidating the mechanism underlying muscle development, which could provide valuable information for pig meat quality improvement

Effect of breathing on venous return during delayed cord clamping: an observational study

Real-time echocardiographic monitoring of blood flow in the ductus venosus and hepatic vein was undertaken during perinatal transition with intact umbilical cord of term born infants. Antegrade flow increased during inspiration, preferentially directing blood flow from the ductus venosus into the right atrium.Objective To investigate the effect of spontaneous breathing on venous return in term infants during delayed cord clamping at birth. Methods Echocardiographic ultrasound recordings were obtained directly after birth in healthy term-born infants. A subcostal view was used to obtain an optimal view of the inferior vena cava (IVC) entering the right atrium, including both the ductus venosus (DV) and the hepatic vein (HV). Colour Doppler was used to assess flow direction and flow velocity. Recordings continued until the umbilical cord was clamped and were stored in digital format for offline analyses. Results Ultrasound recordings were obtained in 15 infants, with a median (IQR) gestational age of 39.6 (39.0-40.9) weeks and a birth weight of 3560 (3195-4205) g. Flow was observed to be antegrade in the DV and HV in 98% and 82% of inspirations, respectively, with flow velocity increasing in 74% of inspirations. Retrograde flow in the DV was observed sporadically and only occurred during expiration. Collapse of the IVC occurred during 58% of inspirations and all occurred caudal to the DV inlet (100%). Conclusion Spontaneous breathing was associated with collapse of the IVC and increased antegrade DV and HV flow velocity during inspiration. Therefore, inspiration appears to preferentially direct blood flow from the DV into the right atrium. This indicates that inspiration could be a factor driving placental transfusion in infants.Research into fetal development and medicin

Feasibility and reliability of PRISMA-Medical for specialty-based incident analysis

Aims and objectives: In this study, the feasibility and reliability of the Prevention Recovery Information System for Monitoring and Analysis (PRISMA)-Medical method for systematic, specialty-based analysis and classification of incidents in the neonatal intensive care unit (NICU) were determined. Methods: After the introduction of a Neonatology System for Analysis and Feedback on Medical Events (NEOSAFE) in eight tertiary care NICUs and one paediatric surgical ICU, PRISMA-Medical was started to be used to identify root causes of voluntary reported incidents by multidisciplinary unit patient safety committees. Committee members were PRISMA-trained and familiar with the department and its processes. In this study, the results of PRISMA-analysis of incidents reported during the first year are described. At t¿=¿3 months and t¿=¿12 months after introduction, test cases were performed to measure agreement at three levels of root cause classification using PRISMA-Medical. Inter-rater reliability was determined by calculating generalised ¿ values for each level of classification. Results: During the study period, 981 out of 1786 eligible incidents (55%) were analysed for underlying root causes. In total, 2313 root causes were identified and classified, giving an average of 2.4 root causes for every incident. Although substantial agreement (¿ 0.70–0.81) was reached at the main level of root cause classification of the test cases (discrimination between technical, organisational and human failure) and agreement among the committees at the second level (discrimination between skill-based, rule-based and knowledge-based errors) was acceptable (¿ 0.53–0.59), discrimination between rule-based errors (the third level of classification) was more difficult to assess (¿ 0.40–0.47). Conclusion: With some restraints, PRISMA-Medical proves to be both feasible and acceptably reliable to identify and classify multiple causes of medical events in the NICU